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  • WCLC 2016

    17th World Conference on Lung Cancer

    Access to all presentations that occur during the 17th World Conference on Lung Cancer in Vienna, Austria

    Presentation Date(s):
    • Dec 4 - 7, 2016
    • Total Presentations: 2466

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    P1.04 - Poster Session with Presenters Present (ID 456)

    • Type: Poster Presenters Present
    • Track: Pulmonology
    • Presentations: 28
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      P1.04-001 - EGFR, EML4-ALK, ROS 1 and BRAF Testing in Austrian Patients with NSCLC: A Multicentre Study (ID 4449)

      14:30 - 15:45  |  Author(s): S. Holzer, M.J. Hochmair, U. Setinek, D. Krenbek, H. Fabikan, R. Rumbold, A. Mohn-Staudner, K. Kirchbacher, M. Arns, T. Bundalo, K. Patocka, O. Burghuber

      • Abstract
      • Slides

      Background:
      Targeted therapy is becoming increasingly important and has improved the overall survival for patients with NSCLC. EGFR and BRAF mutations, EML4-ALK and ROS1 translocations are current allocatable targets. The incidence of these druggable targets in Austria is unknown.

      Methods:
      Tumor tissue from bronchoscopy, CT- and ultrasound guided biopsies as well as surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) were routinely analyzed independent of the tumor stage and clinical characteristics (reflex testing) for these genetic alterations. Since January 2010 the EGFR mutation detection was performed with the EGFR Mutation Test Kit from ROCHE on a COBAS4800. Since August 2011 tumor tissue was analyzed for EML4-ALK with a two-step procedure. First an immunohistochemical staining was done with the Ventana anti ALK(D5F3), OptiView DAB IHC DetectionKit and OptiViewAmplifikationKit® and further on positive cases were tested by PCR (AmoyDx®EML4-ALK FusionGeneDetectionKit) or ALK FISH (dual colour breakapart FISH/Abbott Vysis®). Since January 2014 the tumor tissue was analyzed for ROS1 with a two-step procedure. First an immunohistochemical staining was done with ROS1 D4D6, cell signaling® and further on positive cases were tested by PCR (AmoyDx®ROS1 GeneFusionDetectionKit) or ROS1 FISH (ROS1-6q22.1 dual colour breakapart probe ZytoVision®). BRAF testing was performed with the cobas®4800BRAF V600Mutation Test from Roche since March 2016.

      Results:
      An EGFR Mutation was found in 340 out of 2776 patients (12.2%). 253 patients (9.1%) carried an activated mutation (Exon 19 Deletion, Exon 21 L858R). EML4-ALK positive translocation was found in 100 out of 2212 patients (4.5%). ROS1 positive translocation was found in 5 out of 1060 patients (0.5%). BRAF mutation was found in 3 patients out of 40 (7.5%).

      Conclusion:
      Frequency of these genetic alterations in Austrian patients with NSCLC was quite similar to other Caucasian peers. Therefore reflex testing is recommended independent of any clinical characterization.

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      P1.04-002 - Positive Airway Pressure-Enhanced CT to Improve Virtual Bronchoscopic Navigation (ID 4869)

      14:30 - 15:45  |  Author(s): M. Diez-Ferrer, D. Gil, E. Carreño, S. Padrones, S. Aso, V. Vicens, N. Cubero, R. Lopez-Lisbona, C. Sanchez, A. Borras, J. Dorca, A. Rosell

      • Abstract
      • Slides

      Background:
      A main weakness of virtual bronchoscopic navigation (VBN) is unsuccessful segmentation of distal branches approaching peripheral pulmonary nodules (PPN). CT scan acquisition protocol is pivotal for segmentation covering the utmost periphery. We hypothesize that application of continuous positive airway pressure (CPAP) during CT acquisition could improve visualization and segmentation of peripheral bronchi. The purpose of the present pilot study is to compare quality of segmentations under 4 CT acquisition modes: inspiration (INSP), expiration (EXP) and both with CPAP (INSP-CPAP and EXP-CPAP).

      Methods:
      In 10 patients 320-detector row CT scans with slice thickness of 0.5 mm were performed in the 4 modes. In first 5 patients a pressure ranging 6-10 cmH~2~O was applied for 3 min immediately before CT acquisition (CPAP6-10). In following 5 a pressure of 10 cmH~2~O was applied, followed by 3 min of expiratory maneuvers and non-CPAP acquisitions (CPAP10). Segmentations were obtained and measurements manually calculated with a VBN system (LungPoint, Broncus Technologies, Inc., Mountain View, CA, USA). Comparisons for the inspiratory and expiratory models were made upon main airways area (proximal trachea, distal trachea and main bronchi) and distance of the path to the nodule (DIST-PN). Also, 2 random bronchi per lobe were selected and the number of bifurcations (BIF) and distance (DIST) from carina to the very end of the selected bronchi were manually counted and median calculated. Statistical analyses with R-3.2.3.

      Results:
      See table 1.Figure 1



      Conclusion:
      A tendency towards enlargement and improved segmentation of airways is seen with the use of CPAP in both levels of pressure. However, the power of this pilot study is limited and larger studies might be encouraged. Funded by La MaratóTV3-20133510, FIS PI09/90917, DPI2015-65286-R, 2014-SGR-1470, PROD-2014-00065, FUCAP and SEPAR.

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      P1.04-003 - Incidence of Non-Caseating Granulomas Diagnosed in PET Avid Mediastinal/Hilar Nodes in Patients with Known Breast Cancer (ID 4189)

      14:30 - 15:45  |  Author(s): T. Webb, I. Bonta, P. Thompson, C. Parks, R. Bechara, D. Miller

      • Abstract

      Background:
      Breast cancer is known to metastasize to the lung.. Most breast malignancies are clinically staged using radiographic modalities (e.g. PET scans). Importantly, many inflammatory disorders will present similar lymph node FDG-uptake on PET- as that of metastasized breast cancer. The latter confuses the treatment for individuals within whom both undiagnosed autoimmune disorders and breast cancer co-occur. We aim to examine the frequency of non-caseating granulomas diagnosed in PET avid mediastinal/hilar nodes in patients with known breast cancer.

      Methods:
      Between March 2013 and December 2015, 46 patients diagnosed with breast cancer were staged by PET-CT. Those with positive result in the mediastinum/hilum underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis and ensuing treatment

      Results:
      Of the 46 patients with avid mediastinal/hilar adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had positive PET but negative cytology for malignancy. Twelve of the 15 patients with false positive PET had reactive lymph nodes, and 3 had non-caseating granulomas on cytology (table 1). . Table 1: Results from EBUS Procedure and Resulting Percentage Following Identification of Sarcoid-like Symptoms

      Total Number of patients in study: n=46 with positive PET Number of patients Percentage of total (all PET positive patients) Percentage among negative patients
      Positive EBUS 31 67.40%
      Negative EBUS 12 26.10% 80%
      Negative/Non-caseating granulomas EBUS 3 6.50% 20%
      Twenty percent of the patients with negative cytology and positive PET had non-caseating granuloma, and 6.5 % of all patients with positive PET had non-caseating granulomas.

      Conclusion:
      Conclusion: This study represents the largest cohort of breast cancer patients, where the incidence of non-caseating granulomas is investigated in PET-positive mediastinal/hilar nodes. We conclude that PET may not be sufficient for staging the mediastinum in patients with breast cancer and, in selected patients, pathologic staging should be done. In addition, the finding of non-caseating granulomas in these patients may either indicate an incidental diagnosis of early stage sarcoidosis, or an inflammatory reaction to the current treatment (sarcomatoid reaction). We also suggest that these patients should be followed for any manifestations of sarcoidosis.

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      P1.04-004 - Bronchocopic Cryosurgery with Carbon Dioxide; Experience in an Oncology Clinic in Colombia (ID 5528)

      14:30 - 15:45  |  Author(s): J. Sanchez Vallejo, J.A. Echeverri, J.C. Rojas Puentes, A. Angel Henao

      • Abstract

      Background:
      The bronchoscopic cryosurgery with carbon dioxide is a groundbreaking tool in the diagnostic treatment of respiratory diseases. It has shown to be of great usefulness at a reasonable cost, with multiple indications and few side effects. We described the experience in an oncology institution in Colombia.

      Methods:
      Medical histories, Bronchoscopies and images were reviewe from patients subjected to Bronchoscopic Cryosurgery. The procedures were performed at the "High-Tech Western Oncologist Clinic" in Pereira, Colombia with a highly trained medical staff from this clinic and from Neumovida Clinic from Armenia. Rigid and flexible Bronchoscopy video was made, and the equipment used in the cryotherapy was the Erbe Cryo 2 with the cryoprobe of 1.9 and 2.4 mm.

      Results:
      71 patients were found, 44 men, 27 women. Tracheal Recanalization to 11 patients, Bronchial Cryorecanalization to 24, Bronchial Cryobiopsy to 13, Tracheal Cryobiopsy to 7 and Pulmonary Cryobiopsy to 16 patients. Cryorecanalization was performed to 15 patients with tumors in the right lung and 9 in the left lung. Permeabilization of the Bronchial lumen was achieved to 22 patients at the same time the Bronchoscopy was being done. In 2 patients with Bronchial Obstruction the same procedure was achieved a week later. Pulmonary re-expansion and symptomatic control were achieved in 31 patients. Permeabilization of the bronchial lumen was achieved in 2 patients but not pulmonary re expansion. Silicone prosthesis were implanted to 9 patients with Tracheal lesions and 18 patients with Bronchial lesions. Differences between genders were not shown. There were not any important clinical complications associated with the procedures. Moderate bleeding with the pulmonary biopsy was control locally. In general the post operative evolution of the patients was satisfactory.

      Conclusion:
      The Bronchoscopic Cryosurgery has clear indications in patients with Central Airway Tumors, just as the diagnostic, therapeutic and palliatives purposes and in patients with interstitial compromise of presumable neoplasic or infectious origin. In our casuistry, the objective was achieved in all the patients that underwent the procedures such as tracheobronchial recanalization and extraction of tracheal, bronchial or pulmonary tissue with a significant symptomatic improvement with a low risk and low morbidity

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      P1.04-005 - Efficacy of Photodynamic Therapy Combined with a Guide Sheath Method in Lung Cancer Patients with Endobronchial Stenosis (ID 3679)

      14:30 - 15:45  |  Author(s): M. Misawa, F. Suzuki, S. Yamawaki, R. Tsuzuki, A. Otsuki, K. Nakashima, S. Noma, M. Aoshima

      • Abstract

      Background:
      Photodynamic therapy (PDT) using a second generation of photosensitizier, talaporfin sodium was useful for the curative or palliative treatment of lung cancer. However, it is required for interventional pulmonologist to perform accurate PD-laser irradiation in some lung cancer case. We hypothesized that all-direction type PD-laser probe covered with a guide sheath (GS) (GS-PDT) made it possible to secure its probe and fix its position in the endobronchial lesion, to enhance the effect of PDT by avoiding direct contact with the tumor lesion, thus preventing its probe from contact with blood.

      Methods:
      We evaluated the efficacy and safety of this irradiation technique for the lung cancer patients with endobronchial stenosis. Before the procedure, we evaluated the extent of tumor lesion by auto-fluorescence video-bronchoscope (BF TYPE-F260, Olympus, Japan). As a photosensitizer, talaporfin sodium (Laserphyrin, Meiji Pharma, Japan) was administered at 40mg/m[2 ]intravenously 6 hours before irradiation. PDT was performed by using video-bronchoscope (EB-530T, FUJI MEDICAL, Japan) to visualize PD-laser light clearly by adjusting FICE(Flexible spectral Imaging Color Enhancement)mode. We irradiated 664nm laser light to the target bronchus with endobronchial stenosis utilizing an all-direction type laser probe covered with a GS (disposable K203 guide sheath kit, Olympus, Japan) at each dose of 100J/cm[2] (150mW) for 11 minutes and 7 seconds under fluoroscopic guidance. After one month, we evaluated the endoscopic efficacy of this method.

      Results:
      Between December 2014 and April 2015, we performed GS-PDT for three patients with pathologically diagnosed lung cancer, 1 squamous cell carcinoma, 1 adenocarcinoma and 1 small cell carcinoma. Stage IA squamous cell carcinoma patient with endobronchial stenosis underwent definitive therapy. Stage IA adenocarcinoma patient with endobronchial wall spread of tumor to proximal respiratory tract underwent a combination of induction chemo-radiotherapy followed by sleeve left upper lobectomy as for definitive therapy to reduce the extent of lung resection. Stage IIIA limited-stage small-cell lung cancer patient with the stenosis of right main and upper lobe bronchus underwent palliative therapy to improve oxygenation and to prevent obstructive pneumonia. One month after GS-PDT, we confirmed the endoscopic response (1 complete response, 2 partial response). No PDT-related complications occurred.

      Conclusion:
      New GS-PDT method was safe and could be an effective technique to accurately irradiate the lung cancer patients with endobronchial stenosis.

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      P1.04-006 - Second Primary Lung Cancer: Five Years of a Single Center Experience in Its Diagnosis and Treatment (ID 4626)

      14:30 - 15:45  |  Author(s): F. Caushi, D. Xhemalaj, H. Hafizi, I. Skenduli, J. Shkurti, A. Mezini, Z. Pupla, A. Hatibi

      • Abstract
      • Slides

      Background:
      Second primary lung cancer (SPLC) constitute an important dimension of the burden of cancer survivorship that needs to be taken into account when defining strategies for surveillance, prevention and counseling. In last three decades the incidence of SPLC in patients that had a history of a prior cancer out of the respiratory system is estimated 2-8%. Relative risks of SPLC may be smaller than previously reported may benefit from increased surveillance. The goal of this study was to give an overview of SPLC regarding patients’ primary malignancy, their stage of lung cancer presentation and bringing to the light some possible risk factors. Such data will be helpful in calculation of the risk for SPLC as well as handling of risky patients for a better survival.

      Methods:
      This is a retrospective study for a period of 5 years where all the data that was gathered from clinical cartels of patients with lung cancer were analyzed using Pearson Chi-Square.

      Results:
      SPLC represents 2% of all lung cancers diagnosed during the period of study. The prior diagnose of cancer for this patients was breast cancer in 46% of cases, cervix cancer in 40% of cases and the other diagnosis 14% of cases. All the patients have been under oncologic treatment with radio or chemotherapy. 20% of these patients have been smokers prior to first malignancy. The average age of the patients with SPLC was 55 years old. The ratio male to female was 1:10. The most frequent hystotipe found was adenocarcinoma in 60% of cases meanwhile in all cases with a prior squamous cell cancer of cervix was found squamous cell carcinoma as SPLC. The average period of time from the prime cancer to the SPLC was 3.7 years. 73% of cases with SPLC underwent an anatomical resection of the tumor.

      Conclusion:
      This study shows that patients with the higher risk for a SPLC are premenopausal women with breast cancer and cervical cancer. Changes in the prevalence of risk factors and diagnostic techniques may have affected more recent risks. The relative risk of developing SPLC in smokers is unclear. SPLC after oncologic treatment is an issue that raises many questions.

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      P1.04-007 - Y Stents in Malignant Tumours - Long Time Follow up and Survival (ID 4071)

      14:30 - 15:45  |  Author(s): V. Kolek, R.-. Zittova

      • Abstract

      Background:
      Stent insertion is one of the standard methods of therapeutic bronchology. Stents can be applied to trachea or bronchi. Y stents are inserted to the tracheobronchial area around tracheal bifurcation. The most frequent indications are the central malignant tumours, less frequently benign stenosis, phistulla or tracheomalatia. The prognosis of central stenosing tumours is usually unfavourable with no specific data available.

      Methods:
      464 stents were inserted in our institution, out of them 120 were of Y type. The results of Y stent insertion in malignant tumours during the period 2001- 2015 were evaluated. Survival of patients was compared according to sex, age, tumour origin, histology and stage.

      Results:
      80 Y stents were inserted in 50 men and 30 women, mean age in the time of diagnosis was 61.6 year, in the time of stent insertion 62.8 year. There were 53 bronchial cancers, 6 tracheal cancers, 12 oesophageal cancers, 3 laryngeal cancer, 2 thyroid cancers, and 1 breast cancer, 2 lymphomas, and 1 thymoma. Since diagnosis the mean survival (MS) was 26.39 months, median of overall survival (mOS) was 10.89 (95% CI 8.10- 13.67) months. Since stent insertion MS was 18.09 m and mOS was 3.48 (95% CI 2.72-4.23) m. There were no statistically significant differences according to sex, age and type of tumour (p >0.05): tracheal cancer - mOS 6.07 m, lung cancer - mOS 3.64 m, oesophageal cancer - mOS 2.49 m, other tumours - mOS 3.54 m. Among lung cancers squamous cancer was the most frequent type (34 pts, mOS 4.20 m) and had better prognosis than adenocarcinoma (8 pts, mOS 3.64 m), small cell lung cancer (4 pts, mOS 1.18 m) and NOS (3 pts, mOS 1.80 m). Squamous cancer stage IIIB (22 pts, mOS 5.18 m) had better prognosis than stage IV (10 pts, 3.47 m), all differences were not significant.

      Conclusion:
      Y stent insertion is an effective palliative procedure in malignant stenosis of central airways. Tumours in this localisation have generally bad prognosis. In present study, squamous lung cancer was the most frequent one and had longer survival than other types of cancers. Study was supported by grant AZV 16-32318A

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      P1.04-008 - Tumor Pentaplicity - Case Report (ID 4658)

      14:30 - 15:45  |  Author(s): P. Smičková

      • Abstract
      • Slides

      Background:
      Metachronic tumor duplicity is a relatively common phenomenon, often related to mutagenic effects of some types of antitumor therapy. However, idiopathic tumor multiplicity is rare. We present the case report of a patient, who developed five different malignant tumors in fifteen years horizon.

      Methods:
      Case report

      Results:
      66-year old patient was diagnosed renal cell carcinoma in year 2001 with subsequent nephrectomy. During follow-up, a coin lesion was recognized on chest x-ray, histologically and radiologically verified as stage IA pulmonary adenocarcinoma. Patient underwent successful right lower lobectomy. In 2010 colorectal carcinoma was diagnosed followed by non-invasive papillocarcinoma of urinary bladder in 2012. All these tumors were treated curatively. In 2014 a new mass appeared on chest x-ray. Repeated bronchoscopy failed to obtain valid histological sample. The positron emission tomography revealed malignancy suspicion and excluded the disseminated disease. Surgical resection was performed. Peroperative histology reported carcinoma of uncertain type and surgeon decided for completion of pulmonectomy. However, final histological report showed small-cell lung cancer (pT2apN2Mx). Despite adjuvant chemotherapy given the patient developed distant metastases and died subsequently due to tumor progression in February 2016.

      Conclusion:
      Tumor pentaplicity is a clinical situation with rare occurrence. Our patient didn´t receive chemotherapy until 2010 (adjuvant chemotherapy after radical colorectal carcinoma surgery), so there could be no influence of the first three malignancies therapy. We did not find tumor occurrence in the family, no external risk factor, the patient fits in none of defined hereditary cancer predisposition disorder. Detection of common driver mutations in all five tumors is running. The long term survival is supporting the idea of a careful follow up and shows advances in current oncological treatment.

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      P1.04-009 - Bacterial Population Dynamics in Colonization of Airway Stents in Patients with Cancer (ID 4906)

      14:30 - 15:45  |  Author(s): M. Diez-Ferrer, L. Calatayud, C. Lopez-Delgado, R. Lopez-Lisbona, N. Cubero, N. Koufos, S. Marti, C. Ardanuy, J. Dorca, J. Liñares, A. Rosell

      • Abstract

      Background:
      Stent placement is an increasingly used treatment for malignant tracheobronchial stenosis. The main complication related to airway stents is bacterial colonization causing chronic cough and sputum, halitosis, recurrent bronchial infections, pneumonia and even sepsis. The main objectives were to describe potentially pathogenic bacteria (PPM) involved in stent colonization and to analyze PPM dynamics during follow-up.

      Methods:
      Prospective study in patients with malignant stenosis treated with stent placement. Bronchial washings (BW) were performed before and at least 1 month after stent placement. Qualitative cultures of PPM isolated in BW were performed. Statistical analyses with R-3.2.3.

      Results:
      Total of 65 patients, 56 (86%) men, mean age 64 (±10) y/o, 58 (89%) current or former smokers, 2 (3%) bronchiectasis, 28 (43%) COPD. Cancers were: primary lung cancer (n=52, 80%) followed by thyroid (n=4, 6%), esophagus (n=2, 3%) and other (n=7, 11%); stenosis were located in trachea (n=14, 21%), main carina (n=16, 25%) and main bronchi (n=35, 54%); and stent types included metal (n=30, 46%) and silicone (n=35, 54%). Isolated PPM in BW (table 1). Airway colonization was absent in 14 (21.5%) and present in 79%, of which it was persistent in 33 (50.8%) and intermittent in 16 (24.6%). Only 2 (3.1%) became negative. Median time until colonization was 35 days (IQR 28-116), with no significant differences between stent types or location. Figure 1



      Conclusion:
      The majority of patients with malignant stenosis treated with airway stents develop early and persistent colonization by PPM, regardless of stent type.

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      P1.04-010 - Neutrophil to Lymphocyte, Platelet to Lymphocyte Ratios and Systemic Inflammation in Lung Cancer Stages (ID 6169)

      14:30 - 15:45  |  Author(s): E. Ionela Mihaela, D. Stefan, S. Carmen, B. Miron

      • Abstract
      • Slides

      Background:
      Lung cancer is associated with systemic inflammation which seems to influence the prognostic of the disease. Different affordable methods may be used to evaluate the systemic inflammation: erythrocyte sedimentation rate (ESR), Neutrophil to lymphocyte ratio (Ne/Ly), Platelet to lymphocyte ratio (Pl/Ly). The aim of the study is to assess the relation between TNM lung cancer stages and the systemic inflammation estimated by Ne/Ly, Pl/Ly and ESR.

      Methods:
      Patients with lung cancer were classified according to 7[th] TNM lung cancer staging in two groups: Group A (I, II and IIIA) and Group B (IIIB, IV). A complete blood count (CBC) and ESR were determined. Ne/Ly and Pl/Ly ratios were calculated for all patients. The results were compared between the two groups.

      Results:
      73 consecutive patients (22 in Group A and 51 in group B) were analyzed. In Group A (16 males), the mean age was 63,73 ± 7,69 years, the median Ne/Ly: 2,86 (0,88-8,36), median Pl/Ly: 128,81 (21,62-416,67) and median ESR: 10 mm/h (10-120). In Group B (48 males), the mean age was 65,06 ± 10,09 years, the median Ne/Ly: 4,46 (0,70-25,6), median Pl/Ly: 204,48 (3,38-651,25) and median ESR: 40 mm/h (3-120). The values of Ne/Ly, Pl/Ly were significantly higher (p: 0,009 respectively p: 0,007) in Group B versus Group A, but no statistically significant difference was observed for ESR values.

      Conclusion:
      We found a relation between TNM lung cancer stages and the systemic inflammation assessed by neutrophil to lymphocyte (Ne/Ly) and platelet to lymphocyte (Pl/Ly) ratios. The values of Ne/Ly, Pl/Ly ratios were significantly higher in nonresectable stages (IIIB, IV).Erythrocyte sedimentation rate (ESR) seems not to be an appropriate method to evaluate this relation.

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      P1.04-011 - Demographic, Clinical and Survival Characteristics of Lung Cancer among Elderly Patients in Turkey (ID 6155)

      14:30 - 15:45  |  Author(s): G. Ak, S. Metintas, S. Yilmaz, F. Bogar, M. Metintas

      • Abstract
      • Slides

      Background:
      To determine demographic, clinical and survival data of elderly lung cancer patients.

      Methods:
      We evaluated 2,637 patients with lung cancer between January 1990 and October 2010. Elderly patients were defined as those 65 years or older. The patients were classified into two groups: younger and older group. The demographic, clinical and survival data of the groups were compared.

      Results:
      998 (37.8%) patients were in the older group and 1,639 (62.2%) were in the younger group. The female patients rate (9.1% vs 7.8%; p=0.238) and other cancer history (4.4% vs 3.3%; p=0.101), and family cancer history rate (p=0.664) were similar between two groups. Illiterate patients rate (20.1% vs 16.6%; p<0.001), occupational risks (9.2% vs 12.8%; p=0.005), current smoker and exsmoker rate (p<0.001), asbestos exposure rate (p=0.005), COPD prevalence (15.1% vs 8.6%; p<0.001), and two or more comorbidity rate (21.1% vs 10.1%; p<0.001) of older group was higher than younger group. The symptom duration of the groups were 96.4 days and 92.8 days, respectively (p=0.359). Systemic complaints and extrapulmonary intrathoracic spread complaints of older group were higher than younger group (p<0.001 and p=0.025). Karnosfky performance status was lower in older group than younger group (79.3 vs 82.2; p<0.001). Radiological findings of asbestos exposure was higher in the older group than younger group (6.9% vs 4.1%; p=0.002). There was no difference between the groups in terms of histology and stage (p=0.078 and p=0.254). The independent etiological risk factors of lung cancer in elderly patients were lower educational status, smoking, COPD and male gender by multivariable logistic regression analysis. The median survival was 8.0 ± 0.36 months (95% CI: 7,288-8,712) for older group and 9.0 ± 0.27 months (95% CI: 8,477-9,523) for younger group (log-Rank: 4.567; p=0.033). The factors affecting survival in the both groups stage, Karnofsky performance status and treatment by Cox regression analysis.

      Conclusion:
      These data indicate that lung cancer had different risk factors and short survival in elderly patients. These features should be considered in the management of these patients.

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      P1.04-012 - Single Center Experience with Nivolumab Administration in NSCLC Patients from EAP Program (ID 4862)

      14:30 - 15:45  |  Author(s): M. Pesek, J.-. Durova, G.-. Krakorova

      • Abstract

      Background:
      Immunotherapy using monoclonal antibody against PD-1 receptor (nivolumab) offers another possibility to improve tumor control in patients with advanced squamous (SQ) and non-squamous (NSQ) NSCLC.

      Methods:
      We present first experience with nivolumab in Early Access Program (EAP). Nivolumab tolerability, safety data, frequency of therapeutic responses and ADRs will be presented in 42 patients with advanced SQ and NSQ NSCLC.

      Results:
      22 patients with SQ-NSCLC entered EAP, 3 patients did not start therapy (2 early deaths and 1 refusal) and 19 patients received treatment (16 males, 3 females). Therapy was discontinued in 9 patients (7x disease progression, 2x serious ADR). Therapy is currently withold in 4 patients due to management of ADRs and 7 patients continue to receive nivolumab. 5 patients died (26%) with median follow up of 9 months in this group. 20 patients with NSQ histology were included in EAP, 2 patients from this group died before initiation of therapy and 1 patient did not receive nivolumab due to worsening of her performance status. 17 patients were treated with at least one dose of nivolumab (10 males, 7 females). Therapy was discontinued in 8 patients (7x disease progression, 1x due to gastrointestinal toxicity with grade 3 diarrhea). Treatment is currently withold in 6 patients due to management of ADRs and 4 patients continue to receive nivolumab. 5 patients (29%) in this group died with median follow up of 5 months. So far, we have seen 7 partial remissions in all 36 treated patients with NSCLC (19%) which corresponds to data from registration studies of nivolumab. Disease stabilization was reported in other 7 patients giving the disease control rate of 38%. As expected from nivolumab mechanism of action, adverse drug reactions are usually immune related. Serious ADRs were rarely observed including neurological toxicity (difficulty to swallow and diplopia), diarrhea, pneumonitis and skin toxicity (lichen ruber planus).

      Conclusion:
      In general, patients from EAP program were more pretreated compared to patients in registration studies (therapy allowed in 3rd and 4th line), also patients with PS2 were included (only PS 0 and 1 in the trials). Treatment with nivolumab was well tolerated and it brings the benefit for some patients after 1-3 lines of previous anticancer therapy. Although serious ADRs are relatively rare, management of side effects requires good cooperation with the patients as well as cooperation with highly specialized departments (gastroenterologists, endocrinologists, dermatologists).

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      P1.04-013 - Diagnostics and Treatment of ALK-Positive NSCLC Patients - A Single Center Experience (ID 5152)

      14:30 - 15:45  |  Author(s): M. Pesek, P.-. Grossmann, P.-. Mukensnabl, G.-. Krakorova

      • Abstract

      Background:
      ALK positive advanced NSCLC patients could get significant benefit of targeted therapy. In Czech Republic, targeted therapy is payed just as second-and more line treatment, required positive FISH result of ALK-positive NSCLC tumour.

      Methods:
      We investigate ALK-rearrangement in selected group of NSCLC patients starting from January 2011 via fluorescence in situ hybridization (FISH) with the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular). We evaluate frequence of positive and inconclusive results. In the group of ALK positive patients we evaluate clinical behaviour of tumours and effectivity and side effects of ALK inhibitors.

      Results:
      From January 2011 till June 2016, 798 nonsquamous NSCLC tumour samples were evaluated by FISH method. 20 (3.2 %) of evaluable 660 samples were positive, 138 tumour samples were clasified as ALK break inconclusive (17.3 %). ALK break positive group of patients consist of 13 men and 7 women, median age 68.5 years. 17 of them were adenocarcinomas, in two there were adenosquamous histology and in one NSCLC-NOS was found. The limit of ALK positivity was 10 % positive cells, the range of our positive results were 10 – 72 %. 6/20 patients were treated by crizotinib. Two of them received second ALK inhibitor ceritinib after failure of crizotinib, those patients are alive and well 5 and 8 years from diagnosis of adenocarcinoma st. IV. Three patients died before they could get an access to targeted therapy, seven others with low PS died before start of targeted therapy, in three others there is not actual need for targeted treatment. One patient on crizotinib died after 11 months of targeted treatment, two other died after one month of treatment, in one patient targeted therapy was refused due to intolerance.

      Conclusion:
      Patients suffering from advanced ALK rearranged NSCLC should have perspectives of long lasting tumour response on ALK inhibitors. ALK rearrangement investigations should be done in nonsquamous NSCLC routinely. In our departments, we have relatively high frequency of inconclusive ALK testing results. However, it is not easy to get adequate tissue sample from routine investigations. Positive results are found most frequently in adenocarcinoma patients. We consider due to rapid progression of ALK positive tumours on chemotherapy that targeted therapy should be realised as a first line option.

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      P1.04-014 - Diagnostic Yield in Patients Undergoing Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Diagnosis of Lung Cancer (ID 4791)

      14:30 - 15:45  |  Author(s): S. Touray, R.N. Sood, C. Martinez-Balzano, J. Holdorf, A.T. Lim, A. Sosa, P.J. Oliveira, S.E. Kopec

      • Abstract

      Background:
      Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is an established diagnostic tool in the evaluation of lung cancer with a variable diagnostic yield, ranging from 62 % - 93 %[1–4]. Although the procedure can be performed under moderate sedation (MS) or general anesthesia (GA) [5], the impact of sedation type on the diagnostic yield has yielded variable results with some authors reporting a higher yield with deep sedation[6], whereas others note no difference between MS and GA[5]. We present findings of a retrospective study that looked at the diagnostic yield using an artificial airway under GA compared to conscious sedation through a natural airway in patients undergoing EBUS-TBNA .

      Methods:
      Demographic information on age, sex, race and co-morbidities were used to compute an age adjusted Charlson Co-morbidity index for each of 88 patients. Pathology reports were reviewed and an EBUS-TBNA was determined to be diagnostic if any of the sampled lymph nodes yielded a diagnosis. Assessment of the impact of using an artificial airway under GA on diagnostic yield was determined using multivariate logistic regression. Continuous variables are presented as means (± SD) and categorical variables are reported as counts and percentages. For all tests, two-sided P values < 0.05 were considered statistically significant.

      Results:
      Patients in the GA group were older (65 years versus 57.6, p= 0.005), had a higher age-adjusted Charlson comorbidity index, (3.7 versus 1.9, p < 0.001) and a higher ASA classification (3 versus 2 p=0.004). Average lymph node size was smaller in the artificial airway group (16.2 mm versus 20.7mm, p = 0.01). Despite these differences, the diagnostic yield was the same (61.4 % in each group). In multivariate analyses, female sex and lymph node size were the only predictors of a diagnostic EBUS-TBNA. OR 3.3, 95 % CI, 1.23 – 9.1 for female gender, (p= 0.02) and 1.1, 95 % CI, 1.00 – 1.18 for lymph node size (p= 0.04). Diagnoses made were: adenocarcinoma of the lung 42.6 %, Sarcoidosis 16.7 %, Small cell lung cancer 14.8 %, Squamous cell carcinoma 11.1 %.

      Conclusion:
      EBUS-TBNA performed under general anesthesia through an artificial airway was not associated with an increased diagnostic yield, and therefore concious sedation should be considered where appropriate, with general anesthesia reserved for those patients who are older, and with a higher perioperative risk. More research assessing the determinants of a positive diagnosis including physician pretest likelihood and PET/CT avidity are needed to improve diagnostic outcomes.

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      P1.04-015 - Clinical Application of Virtual Navigated Bronchial Intervention (ID 4996)

      14:30 - 15:45  |  Author(s): N. Kajiwara, J. Maeda, K. Yoshida, M. Hagiwara, T. Okano, M. Kakihana, T. Ohira, N. Ikeda

      • Abstract
      • Slides

      Background:
      Removal of endobronchial tumor is considered the first treatment of choice to improve respiratory status to dilate and maintain the airway. In patients with inoperable tumors we frequently regard endoscopic treatment as the first treatment of choice, but the indications and decisions regarding the method require careful consideration. We reported the indications and efficacy of virtual navigated bronchial intervention for the treatment of bronchial tumors. To select safer and precisely approach for patients with bronchial tumors, we evaluate virtual navigated bronchial intervention using a high-speed 3-dimensional (3D) image analysis system, Synapse Vincent (Fuji Photo Film Co., Ltd., Tokyo, Japan).

      Methods:
      We set out to clarify, based on retrospective evaluation of routine work-up data in our charts and patient treatment data, the efficacy of virtual navigated bronchial intervention for the treatment of different types of bronchial tumors, yet representative of the spectrum of conditions we encounter, in order to provide a guide to techniques available in interventional bronchology for obstructive lesions. All computed tomography (CT) must satisfy several conditions necessary to analyze images by Synapse Vincent. Synapse Vincent provides more information not only concerning tumor size and shape, but also whether the tumor invades surrounding tissue and the extent of airway and vessel involvement. Constructed images are displayed on a monitor, which can be utilized for deciding the simulation and interventional strategy and for navigation during interventional manipulation.

      Results:
      In these cases, Synapse Vincent was used to determine the best planning of virtual navigated bronchial intervention. The feasibility and safety of Synapse Vincent in performing useful preoperative simulation and navigation of interventional procedures lead to the safer, more precise, and less invasive for the patient, and easy to construct an image, depending on the purpose, in 5-10 minutes using Synapse Vincent. Moreover, if the lesion is in the parenchyma or sub-bronchial lumen, it helps to perform simulation with virtual skeletal subtraction to estimate potential lesion movement. By using virtual navigated system for simulation, bronchial intervention was performed with no complications safely and precisely.

      Conclusion:
      Preoperative simulation using virtual navigated bronchial intervention reduces the surgeon’s stress levels, particularly when highly skilled techniques are needed to operate on lesions. This task, including interventional simulation and navigation both pre- and during manipulation, could lead to greater safety and precision. These technological instruments should be helpful for bronchial intervention procedures, and are also excellent devices for educational training.

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      P1.04-016 - EBUS plus Fluoroscopy-Guided Biopsy Compared to Fluoroscopy-Guided TBB for Obtaining Samples of Peripheral Pulmonary Lesions (ID 3739)

      14:30 - 15:45  |  Author(s): J. Ye

      • Abstract

      Background:
      Early detection of peripheral pulmonary nodules and histopathologic diagnosis of biopsy samples of the nodules are key to improving survival rates of lung cancer. Steady improvement in bronchoscopic procedures during the past few decades enable detection and biopsy of much smaller nodules. We report a meta-analysis of recent reports comparing the diagnostic yields of endobronchial ultrasonography plus fluoroscopically-guided transbronchial biopsy with that of fluoroscopically-guided transbronchial biopsy without the use of endobronchial ultrasonography.

      Methods:
      We searched Medline, the Cochrane Library, PubMed, and Google Scholar and found five articles that met our inclusion criteria. One of those articles did not strictly meet our criteria, in that it was deficient in quantitation, but we included it because it contained other relevant information.

      Results:
      Meta-analysis from the 4 studies revealed a higher positive diagnostic yield in the group with endobronchial ultrasonographic guidance in addition to fluoroscopy than the group diagnosed with only conventional fluoroscopic guidance to the lesion, for large and small lesions.

      Conclusion:
      Obtaining transbronchial biopsy samples for histopathological diagnosis is enhanced by addition of endobronchial ultrasonography to conventional fluoroscopic guidance; this is especially important for patients with small peripheral lung lesions who benefit greatly from early diagnosis.

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      P1.04-017 - The Survival of Our Patients Diagnosed with Lung Cancer in 2013 (ID 5187)

      14:30 - 15:45  |  Author(s): S. Altin, C. Ozdemir, C. Kocaturk, M. Kiyik, N. Urer, M.Z. Gunluoglu, K. Kara, S. Hastürk, Y. Baser, M.A. Bedirhan, I. Dincer

      • Abstract

      Background:
      Lung cancer is an important health problem. To investigate the survival of our patients diagnosed in our hospital with lung cancer and the situations that effect.

      Methods:
      Using the data processing and archive system of our hospital , patients were examined who had operated with C34 code in 2013. The rates of survival were calculated using Kaplan-Meier Method and compared with Long-rank method. The influence of age on survival was analysed with Cox’s proportional hazards regression model. For multivariate analysis Cox’s proportional hazards regression model also used. The level of P<0.05 accepted as significant.

      Results:
      1563(83.5%) of 1871 patients were male and 308 of the were female and their average age were found as 62.5 years, the average age in male was 62.7 while 61.4 in female. Median age was 62. The rate of M/F was calculated as 5.1, but there were no difference in terms of the average age(p>0.05). We had 16 male and 11 female patients were about 27(1.4%), under the age of 40. As a histological type, 717(38.3%) were squamous carcinoma, 692(37%) were adenocarcinoma, 288(15,4%) were small cell, 174(9.3%) unidentified cell malign carcinoma. While with 42.8% in male squamous carcinoma was frequent, adenocarcinoma with 57.8% in female was frequent. The average survival was calculated as 18 months, median survival as 12 months (95& Cl 11-13 months) and the rate of 2 years survival as 33,4%. While surgical treatment were applied to 380 patients (20.3%), chemotherapy were applied to 1100 patients(58,8%) and palliative care were applied to 302(16,1%) patients. The 2 years survival time was found significantly high in patients received surgical treatment.(73% in spite of 23.3%)(p<0.0001). While the 2 years survival of patients receiving chemotherapy was calculated as 25,6%, the patients receiving palliative care was 20,5%(p=0.08).The median survival time was found 28,4 months in patients receiving surgical treatment, patients receiving chemotherapy 14 months and palliative care was 11.5 months .The patients received neoadjuvan therapy lived 31months. Evaluation made as multivariate analyses; age, gender, with histological type, the tretament variables one by one were found effective on survival as p=0.0001 level.

      Conclusion:
      It was obtained that the patients diagnosed with lung cancer in our hospital, after they diagnosed they lived averagely 16 months. The patients received surgical treatment with 73%,with 2 years time survival lived significantly more than the other treatments.

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      P1.04-018 - Occurrence of Triple Multiple Malignancies with Last Lung Squamous Cell Carcinoma - Case Reports (ID 5236)

      14:30 - 15:45  |  Author(s): A. Doboszyńska, A.M. Romaszko

      • Abstract
      • Slides

      Background:
      The incidence of multiple primary tumors (MMPNs) ranges from 0.73 to 11.7%. Most often occur double malignancies - 3-5%, much less triples - 0.5%. The aim of the study is to describe the three cases of triple metachronous multiple malignancies, the last of which was a squamous cell carcinoma of lung in all three patients.

      Methods:
      A retrospective analysis of all medical histories (1163) patients who were hospitalized in the Pulmonary Hospital Hospital in Olsztyn, Poland in the period from January 2013 to October 2015, with a diagnosis of at least one neoplasm was performed. We selected only these patients who were diagnosed with histologically confirmed three independent malignancies.

      Results:
      The incidence of tumors of triple malignancies was 0.52%. Of all cases of triple malignancies, we selected 3 cases - 2 men and 1 woman, whose last-growing cancer, histopathologically confirmed, was squamous cell lung cancer. Case No. 1 - 54-year-old man with COPD (GOLD 2), who gave up smoking, melanoma of the scalp treated surgically and by chemotherapy (6xDTIC) at the age of 19, Hodgkin NS II at the age of 38 treated with 6xABVD, at the age of 53 years diagnosed with squamous cell carcinoma of the left lung in stage T2N1M0. Due to the low value of spirometry disqualified from surgery, qualified for radiotherapy. Case No. 2 67-year-old man with a history of hypertension, colon cancer at the age of 56, after a laryngectomy because of laryngeal squamous cell carcinoma at the age of 63, diagnosed with asymptomatic squamous cell carcinoma of the right lung in a stage T2N0M0 at the age of 65. Case No. 3 74-year-old woman with atrial fibrillation, stable ischemic heart disease, tongue cancer at the age of 67, and its recurrence in the age of 72, after a right-sided mastectomy and chemotherapy for breast cancer at the age of 69, at the age of 74 diagnosed with squamous cell carcinoma of the left lung. The average age of first cancer was 47, the second 57 years, the third 64 years.

      Conclusion:
      1. Lung cancer often occurs as a subsequent malignancy 2. Another primary malignancy may develop even 30 years later, and therefore the possibility of development the third or another cancer should be considered for all cancer patients. 3. Development of synchronous or metachronous neoplasms should be considered in any case in patients with previous oncological treatment.

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      P1.04-019 - Final Analysis of Lung Microbiome from Patients Undergoing Bronchoscopy (ID 4201)

      14:30 - 15:45  |  Author(s): G.J. Weiss, J. Cocking, C. Bilagody, H.M. Hornstra, E. Kaufman, D.A. Nader, J.F. Turner, S. Chandrika, J.G. Caporaso, P. Keim, B. Harmon, H. Barilla, T. Pearson

      • Abstract
      • Slides

      Background:
      Recent studies have demonstrated diversity in the lung microbiomes of chronic obstructive pulmonary disease and healthy individuals. Lung microbial communities may not just serve as a predictor of cancer development, but also as a target of pharmacological cancer prevention strategies. We sought to characterize the lung microbiome diversity within patients with lung cancer for comparison to those with other cancers and those without cancer.

      Methods:
      Signed informed consent was obtained from patients ages ≥18 years undergoing a clinically indicated bronchoscopy. A bronchial lavage (BAL) was collected for research purposes after completing routine bronchoscopic procedures. Samples were prepped and DNA was extracted and 515F/806R 16S rRNA primers used to amplify Variable Region 4. Amplicons were sequenced and grouped into 100% operational taxonomic units (OTUs) using vsearch. Taxonomy was assigned, a phylogenetic tree was constructed, and sequences aligned for phylogenetic diversity calculations, including Faith's Phylogenetic Diversity and weighted and unweighted UniFrac. OTUs that were significantly different across sample categories were identified using DESeq2.

      Results:
      There were 137 unique BAL samples collected. One patient had an adverse research procedure event that resolved after temporary supplemental oxygen and overnight observation. BALs were from 68 non-small cell lung cancer (NSCLC), 12 small cell lung cancer (SCLC), 52 other cancers, and 5 non-cancer patients. 58 NSCLC were current/former smokers (average 43 pack-years), while all the SCLC were current/former smokers (average 56 pack-years). 22 other cancers were current/former smokers (average of 27 pack-years). Overall, 51 samples (37.2%) had sufficient sequencing reads (>20,000) for subsequent analyses. There were multiple bacterial taxonomic groups in each sample, however, phylogenetic diversity was low compared to other body sites. There were no statistical differences in alpha/beta diversity between ever-smokers and never-smokers, NSCLC vs SCLC, lung cancer vs non-cancer, and location of BAL collection (upper vs lower airways and right vs left lung). There were a number of statistically significant differences by taxonomy (False Discovery Rate adjusted p<0.01 and listing genus only). Adenocarcinoma vs non-adenocarcinoma had more Streptococcus and Veillonella; less Haemophilus. For NSCLC vs SCLC, Rothia was more prevalent in SCLC. BALs from the upper airways had more prevalent Streptococcus. BALs from the right lung had more prevalent Capnocytophaga and Parvimonas; less Moraxella and Selenomonas.

      Conclusion:
      We report significant taxonomic differences by tumor type and location of BAL sampling and overall low phylogenetic diversity. Future validation of this work can be used to modify bacterial colonization in a lung cancer prevention strategy or for early diagnostics/therapeutics.

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      P1.04-020 - Management of Lung Cancer in Patients with past Pulmonary Tuberculosis and Their Possible Causative Link (ID 4170)

      14:30 - 15:45  |  Author(s): F. Caushi, J. Shkurti, D. Xhemalaj, I. Skenduli, A. Mezini, H. Hafizi, A. Hatibi, I. Bani

      • Abstract
      • Slides

      Background:
      Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. In the past, it was well known that lung cancer is a specific epidemiological successor of pulmonary tuberculosis (PTB) and that it often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. Although studies have found a relationship between PTB and lung cancer, results for the long-term risk and the role of confounding factors remain inconclusive. Therefore, it is important to delineate the relationship between PTB and lung cancer.

      Methods:
      Clinical files of all patients diagnosed with lung malignancy between 2011 and 2016 were investigated retrospectively in terms of patient characteristics, definite histopathological diagnosis and stage of tumor, operation methods, and associated complications.

      Results:
      Mean age was 56.4 years. Past PTB was detected in 3% of operated carcinoma patients and in 6% of all patients diagnosed with lung malignancy. Central lung cancer was diagnosed in 80% of cases and peripheral in 20%. Epidermoid cancer was diagnosed in 51% of cases, adenocarcinoma in 24% and adenoepidermoid carcinoma in 25%. All cases of operable lung cancers were in stage I and II, while inoperable lung cancers were in stage IIIB and IV. Lobectomy was performed in 100% of the operated cases. None of the patients received anti-TB treatment preoperatively or postoperatively because by the time they were diagnosed with lung cancer, their sputum culture for M.Tuberculosis had converted negative. No postoperative mortality or reactivation of TB was seen.

      Conclusion:
      PTB is an important risk factor for lung cancer, possibly related to chronic inflammation and shared risk factors. Our study adds to the evidence that implicates chronic inflammation and pulmonary scarring in the etiology of lung cancer. However, further studies are needed to clarify whether there is a direct causative link between PTB and lung cancer. Surgery is the method of choice in treatment of lung cancer in subjects with past PTB history.

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      P1.04-021 - Medical Thoracoscopy for the Diagnosis and Management of Pleural Effusions: Results of a Retrospective Analysis (ID 4057)

      14:30 - 15:45  |  Author(s): S. Tsagouli, E. Kapetanakis, C. Kampolis, P. Tomos, K. Potaris, E. Kainis, I. Gkiozos, K. Syrigos

      • Abstract
      • Slides

      Background:
      Medical thoracoscopy is a minimally invasive procedure utilized mainly by pulmonologists for the diagnosis and management of pleural effusions. The aim of this study was to evaluate the efficacy and safety of medical thoracoscopy when performed by a combined team of pulmonologists and thoracic surgeons in a tertiary university hospital.

      Methods:
      This is a retrospective cohort analysis of all patients with pleural effusion whο underwent medical thoracoscopy at “LAIKO” Athens General Hospital from June 2013 to December 2014.

      Results:
      Our study population included 36 patients, 18 males and 18 females, with a mean age of 61 years. All patients were submitted to medical thoracoscopy for the diagnostic evaluation of pleural effusion. Twenty-six patients (26/36, 72.2%) presented with an undiagnosed pleural effusion, six (16.7%) with known malignant, recurrent pleural effusion, three (8.3%) with parapneumonic effusion/empyema and one (2.8%) with idiopathic pleural effusion due to nephritic syndrome. Eighteen patients (18/36, 50%) underwent drainage and pleural biopsy, 9 patients (9/36, 25%) underwent drainage, pleural biopsy and talc pleurodesis, 6 patients (6/36, 16.7%) underwent drainage and talc pleurodesis due to known malignant pleural effusion and 3 patients (3/36, 8.3%) underwent drainage of their parapneumonic effusion/empyema. Among all patients (n=27) who underwent diagnostic pleural biopsy, 2 patients (7.4%) were diagnosed with primary non-small cell lung cancer, 4 (14.8%) with malignant pleural mesothelioma, 3 (11.1%) with metastatic disease of non-thoracic primary origin and 3 (11.1%) with lymphoma, while 1 patient each (3.7%) was diagnosed with tuberculosis, systemic lupus eryhtematosus, chronic inflammation, chronic pleural fibrosis and nephritic syndrome. In 3 patients (3/27, 11.1%) the biopsy was negative. Medical thoracoscopy was non-diagnostic in one patient only (1/27, 3.7%), thus producing a diagnostic yield of 97.3%. With the notable exception of one patient (1/36, 2.8%) who died due to empyema and subsequent sepsis, the remaining post procedural complications were mild, and included subcutaneous emphysema in 6 cases (6/36, 16.7%) and minor bleeding in 3 cases (3/36, 8.3%).

      Conclusion:
      When performed by a combined team of pulmonologists and thoracic surgeons in a tertiary level hospital, medical thoracoscopy is a relatively safe and efficacious technique for the diagnosis and management of pleural effusions in patients unable to undergo or not requiring surgical intervention.

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      P1.04-022 - Use of Alternative Therapy in Patients with Lung Cancer (ID 6212)

      14:30 - 15:45  |  Author(s): K.K. Krpina, M.J. Jakopović, M.R. Roglic

      • Abstract
      • Slides

      Background:
      Background: Lung cancer has the highest mortality among all malignant diseases due to advanced stage of diseases at diagnosis, but also due to modest response to therapy. For that reasons an increasing proportion of population use alternative therapy. Most often those are drugs that are alleged immunomodulators However, for systemically administered complementary and alternative medicine (CAM), there are significant risks of adverse drug interactions with conventional treatments, which may result in either increased drug toxicity or therapeutic failure.

      Methods:
      Methods: We performed a retrospective analysis of alternative therapies used during oncology treatment in lung cancer. Data were collected from medical documentation. Total of 246 patients diagnosed with lung cancer at Department of pulmonary diseases Jordanovac were tracked during a two-year period. General information, sociodemographic characteristics and alternative therapies were extractes from documentation and statistically analised.

      Results:
      Results: Total of 76 out of 246 patients (31%) admitted to using alternative therapy. Women use it more often than male (38% vs 28%). No difference was observed according to age o geographic location. Yet there was a small, but significant difference according to level of education. Among patient with university degree 36% used alternative therapy in contrast to 30% among those with high school education. Use of chemotherapy and advanced stage of disease correlated with more frequent CAM use (58% vs 42%). Most often used alternative therapy was aronia (46%) and then cannabis and its derivatives (mostly oil) in 36% of patients, while beta-glucan (11%) and other comprised smaller percentages.

      Conclusion:
      Conclusion: Use of alternative therapies is increasing among patients with lung cancer and it is imperative for physicians to know about this. So far there is no scientific or clinical evidence for positive effects of this therapy, but it is known that it can collide with chemotherapy. Because of that it is imperative to expand our knowledge of use of alternative therapy, as well as its effects.

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      P1.04-023 - Thrombomodulin Inhibits the Growth and Angiogenesis of Human Lung Cancer via Blocking VEGFR2-Mediated JAK/STAT3 Signaling Pathway (ID 4520)

      14:30 - 15:45  |  Author(s): Y. Yi, S. Lu

      • Abstract
      • Slides

      Background:
      Angiogenesis has been an attractive target for drug therapy because of its key role in the growth and metastatic spread of malignant tumor. Thrombomodulin has been shown to possess anti-inflammatory and vascular endothelial protection activities. However, its roles in tumor angiogenesis are unknown. The aim of this study was to investigate the roles of thrombomodulin in tumor angiogenesis and its anticancer activities.

      Methods:
      ex vivo aortic ring angiogenesis sprouting assay was used to detect neo-vascularization. Western blotting was performed to examine STAT3 signaling cascade.

      Results:
      Thrombomodulin significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration and tube formation in vitro and blocked vascular endothelial growth factor (VEGF)-triggered neo-vascularization. VEGF receptor (VEGFR) 2 mediated-Janus Kinase 2/STAT3 signaling pathway was significantly inhibited by thrombomodulin in endothelial cells. In addition, the constitutively activated STAT3 protein, and the expression of STAT3-dependent target genes, including cyclin D1, c-Myc, Bcl-xL, and VEGF were also down-regulated in response for thrombomodulin in human lung cancer cells. Consistent with the above findings, thrombomodulin inhibited tumor cell cycle progression and induced cell apoptosis in vitro.

      Conclusion:
      Therefore, our provided the first evidence that thrombomodulin inhibited tumor angiogenesis and growth via inhibiting VEGFR2-mediated JAK/STAT3 signaling pathway with the potential of a drug candidate for cancer therapy.

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      P1.04-024 - Molecular Profiling and Survival of Primary Pulmonary Neuroendocrine Carcinoma with Completely Resection (ID 4517)

      14:30 - 15:45  |  Author(s): G. Lou, Z. Song, Y. Zhang

      • Abstract
      • Slides

      Background:
      According to the 2015 World Health Organization classification of lung tumors, pulmonary Large cell neuroendocrine carcinoma (PLCNC) is grouped with the small cell lung cancer (SCLC) and carcinoid as pulmonary neuroendocrine carcinoma(PNC) for the common features of neuroendocrine characteristics . Molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma(PNC) are not well investigated currently. We conducted present study to evaluate genomic abnormality and survivals in patients with primary PNC.

      Methods:
      Tumor samples of PNC after completely resection from Zhejiang Cancer Hospital were collected from 2008 to 2015. Nine driver genes including six mutation (EGFR, KRAS, NRAS, PIK3CA, BRAF, HER2) and three fusions (ALK, ROS1, RET) were evaluated by RT-PCR. Survival analysis was evaluated using the Kaplan-Meier method.

      Results:
      Totally, 108 patients with pathologic confirmed PNC were enrolled. Samples included 52 PLCNC, 44 small cell lung cancer (SCLC) and 12 carcinoid. Twelve patients were found to harbor genomic aberrations (11.1%). The most frequent gene abnormality was PIK3CA (n=5,4.6%),followed with EGFR (n=3,2.8%), KRAS (n=2,n=1.9%), ALK (n=1,0.9%), RET (n=1,0.9%). No ROS1,BRAF,NRAS and HER2 mutations were observed. The frequencies of gene aberrations in PLCNC, SCLC and carcinoid were 15.4%,6.8% and 8.3%,respectively. Sixty-seven patients were with recurrence or metastasis after surgery, including 32 PLCNC, 33 of SCLC, and two of carcinoid (both were atypical carcinoid). Among the 32 patients with PLCNC,none received molecular targeted treatment,28 received first-line chemotherapy,including 18 of etoposide/platinum regimen and 10 of other platinum-based treatment. The progression free survival in patients with etoposide/platinum regimen was longer than patients with non-etoposide/platinum treatment (4.8 vs.3.4 months,P=0.019) . Survival difference was observed among the PLCNC,SCLC and carcinoid group (37.0 vs. 34.0 vs.not reached, P=0.035), but no difference existed between the PLCNC and SCLC group (P=0.606) .

      Conclusion:
      Common genomic abnormality is rare in PNC patients and most frequently observed in PLCNC. Patients with carcinoid had a superior survival than PLCNC and SCLC.

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      P1.04-025 - The Impact of Emergency Presentation on Survival of Lung Cancer Patients (ID 5964)

      14:30 - 15:45  |  Author(s): M. Jakopovic, D. Fedza, L. Bitar, I. Markelić, F. Seiwerth, A. Hecimovic, B. Čučević, I. Mazuranic, G. Redzepi, A. Vukic Dugic, M. Jankovic, M. Samarzija

      • Abstract

      Background:
      A significant proportion of lung cancer patients are diagnosed through emergency department (ED), which is usually associated with poorer prognosis. We investigated the assocation between diagnosis of lung cancer after presentation through emergency department due to symptoms associated to lung cancer.

      Methods:
      Medical charts of patients with lung cancer patients newly diagnosed in Department for Respiratory Diseases Jordanovac, University Centre Zagreb in years 2012 and 2103 were reviewed. Overall survival was calculated and was compared between groups.

      Results:
      The medical charts of 951 males and 407 females, mean age 64 years (males 64.5, females 62) were reviewed. 292 out od 1359 patients (21,5%) were diagnosed with lung cancer after initial presentation through ED. The most common reasons for ED admissions were hemopytsis (in 31% of patients), pneumonia (16%), brain metastasis (15%), dyspnea (10%) and superior vena cava syndrome in 8% of patients. There were no differences in histology subptypes between two different routes of presentation (most common histology subtype was adenocarcinoma followed by squamous histology). Significantly higher proportion of patients diagnosed after initial diagnosis through ED were at presentation in stage IV (61 vs 44%, p<0.0001), poorer performance status (ECOG 3-4 vs ECOG 0-1, p<0.0001), significantly less patients underwent surgical resection (14 vs 5%, p<0.0001) and radiotherapy (56 vs 73%, p<0.0001). Median overall survival (mOS) was significantly lower in patients diagnosed through ED (6.0 vs 10.0 months, p<0.0001). In patients with non-small cell lung cancer (NSCLC) results were similar (mOS 6.0 vs 10.0 months, p<0.0001). In patients with small cell lung cancer (SCLC) mOS was also significantly worse (7.0 vs 9.0 months, p<0.0001) in patients diagnosed through ED.

      Conclusion:
      Higher stage, reduced access to surgical resection and radiotherapy, and significantly lower overall survival regardless of histology subtypes among lung cancer patients who presents through emergency department, stress out the importance of earlier diagnosis of lung cancer patients so that initial presentation through emergancy department can be reduced.

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      P1.04-026 - Coexisting Lung Cancer and Interstitial Lung Disease: A Challenge in Clinical Practice (ID 5611)

      14:30 - 15:45  |  Author(s): A. Linhas, D. Machado, S. Conde, S. Campainha, A. Barroso

      • Abstract

      Background:
      Lung cancer (LC) risk is increased in patients with interstitial lung disease (ILD), and the two diseases sometimes occur concomitantly. Cigarette smoking is a recognised risk factor for development of both pathologies but the aetiology and pathogenesis of LC in patients with ILD is still unclear. The benefit of chemotherapy or radiotherapy for LC in cases of ILD remains unknown. Objective: To analyse characteristics and outcomes of patients with ILD and LC.

      Methods:
      A retrospective analysis of all patients presenting with concomitant ILD and lung cancer to our centre, between 1[st] January 2011 and 30[th] June 2016, was performed. Diagnosed lung cancer patients with suspected ILD, but not confirmed, were excluded, as well as patients who developed ILD in the setting of lung cancer therapy. Clinical, radiological and pathological characteristics of this cohort were described. Outcomes were also reported.

      Results:
      Eleven patients were included (mean age 63±12years). Most patients were men (82%) and heavy smokers (64% had a smoking history >30pack/year). The majority ILD cases were related to connective tissue disease (45%) and combined pulmonary fibrosis and emphysema (CPFE) (18%). The most prevalent lung cancer histological type was adenocarcinoma (45%); most patients were diagnosed at advanced stages (63%) and mainly during the clinical and radiological follow-up for the fibrosis. The mean time from the onset of ILD to the onset of LC was 39.4 months. On chest CT, the tumours were predominantly peripheral. Surgical resection was performed in 3 patients with stage I or II LC; chemotherapy and/or radiotherapy were given to 6 patients with advanced disease (stage III and IV). One patient was refused for radiotherapy due to considerations of the adverse effects on the prognosis. The median survival since the diagnosis of LC was 6.7months. Two patients died of respiratory failure due to progression of pneumonitis after the therapy and three patients died due to progression of LC.

      Conclusion:
      Patients with LC and ILD might benefit from chemotherapy and radiotherapy, but pre-existing ILD could influence negatively the prognosis. Therapy for LC should be considered in patients presenting both LC and ILD and interdisciplinary evaluation of therapeutic options is mandatory. When planning radiotherapy it is important determinate the radiation pneumonitis risk. More studies are needed to clarify the role of LC treatment in the management of ILD patients.

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      P1.04-027 - Changes in Pulmonary Function in Lung Cancer Patients after Thoracic Surgery (ID 5619)

      14:30 - 15:45  |  Author(s): A. Linhas, S. Campainha, S. Conde, A. Barroso

      • Abstract

      Background:
      Surgery is considered the first line treatment for patients with resectable early non-small cell lung cancer (NSCLC). Many of these patients present limited lung function which is caused by a common etiologic factor - cigarette smoking. The evaluation of pulmonary function preoperatively is important to identify candidates at risk of postoperative respiratory complications and may assist in operability decision. However, lung function after surgical resection may be affected by several factors. Objective: To evaluate changes in pulmonary function after thoracic surgery, in patients with solitary nodules or lung cancer.

      Methods:
      Retrospective study of patients diagnosed with operable lung cancer and solitary nodules followed in our centre between 1[st] January 2011 and 31[th] December 2014. Patients presenting pulmonary function tests (PFTs) until one year after surgery were included. Patients without PFTs after surgery were excluded.

      Results:
      Forty three patients were included. The results are presented in the table:

      Mean age 62±9 years
      Gender 67,4% (n=29) male
      Indications for surgery Adenocarcinoma Carcinoid tumour Squamous cell carcinoma Solitary pulmonary nodule 44,2%(n=19) 14%(n=6) 11,6% (n=5) 25,6% (n=11)
      Clinical staging in lung cancer patients IA IB IIA IIIA 43,7% (n=14) 15,6% (n=5) 12,5% (n=4) 18,7% (n=6)
      Location of the lesion Superior right lobe Superior left lobe 34,9% (n=15) 25,6% (n=11)
      Neoadjuvant chemotherapy Neoadjuvant radiotherapy 20,9% (n=9) 4,7 (n=2)
      Open surgery Video-assisted thoracic surgery (VATS) 83,7% (n=36) 16,3%(n=7)
      Comorbidities Chronic Obstructive Pulmonary Disease (COPD) Ischemic Heart Disease (IHD) 30,3% (n=13) 4,7% (n=2)
      Smoking habits Smoker Ex-smoker Non-smoker 37,2% (n=16) 32,6% (n=14) 30,2% (n=13)
      The mean values of FVC (L), FEV1 (L), FEV1/FVC and DLCO decreased after surgery (p=0.010, p=0.001, p=0.011 and p=0.037, respectively). FVC (L) and FVC (%) values decreased more significantly in patients submitted to pneumonectomy (p=0.004 and p=0,047). There was, though, an improvement of FVC (%) in patients submitted to VATS and wedge resection (p=0.005 and p=0.034). FEV1 (L) mean values increased in patients submitted to wedge resection (p=0.017) and decreased in patients submitted to pneumonectomy (p=0.04). There was no significant association between histological type, clinical stage, local of the lesion, COPD and CVD and lung function parameters before and after surgery.

      Conclusion:
      The postoperative pulmonary function varied according to the type of surgery, therefore the surgical procedure adopted may help us predict changes in lung function after lung surgery. Clinicians should be aware of these changes when determining the surgical method, especially in high-risk patients.

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      P1.04-028 - Collection of ICHOM-Defined Patient-Reported Outcome Measures (PROMs) during Routine Lung Cancer Treatment: A Pilot Study (ID 5476)

      14:30 - 15:45  |  Author(s): J.P. Van Meerbeeck, L. De Backer, A. Janssens, B. Hiddinga, G. Vanhoutte

      • Abstract

      Background:
      PROMs -including symptoms, health related quality of life, well-being and functional status- are commonly measured in clinical trials. They are used in a variety of ways, including therapy decisions on individual patient level or research into disease progression. Optimizing how patients feel is a goal of good oncology practice and a quality performance indicator of care. Therefore it is important to implement the collection of PROMs during routine lung cancer treatment without disturbing the routine workflow. The International Collaboration on Health Outcomes Measures (ICHOM) has proposed a standard set of uniform PROMs for lung cancer (Mak et al, ERJ 2016).

      Methods:
      A pilot study is set up to establish an operational workflow and to identify trouble shooting to the collection of PROMs in standard of care. Self-reporting by the patient is conducted via a web-based interface using questionnaires and individual case-mix variables according to the ICHOM standard set. At baseline, during treatment and in follow up patients receive electronic invitations. Computer-inexperienced patients have the opportunity to complete paper forms.

      Results:
      A gap analysis was done and a swim lane algorithm constructed which will be presented at the meeting. From February 2016 onwards, 24 patients were screened of whom 11 consented. The other 13 patients were screen failures because of language barrier, previous therapy start or mental confusion. From the enrolled patients, 2 are currently in follow up and 5 patients choose to complete PROMs on paper forms. Updated results on compliance and outcome in 50 patients will be brought at the meeting.

      Conclusion:
      Participants’ profile reflect a tertiary setting hospital with many referrals and patients, unable to complete the PROM’s. To optimize the inclusion rate, several adaptations in the implementation workflow have been introduced. Although the registration of PROMs is not very time-consuming, real-time monitoring requires a user-friendly online tool and dedicated staff. Lessons from this pilot study will be applied when rolling out other ICHOM standard sets.

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    P1.05 - Poster Session with Presenters Present (ID 457)

    • Type: Poster Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 79
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      P1.05-001 - Creation and Early Validation of Prognostic miRNA Signatures for Squamous Cell Lung Carcinoma by the SPECS Lung Consortium (ID 6088)

      14:30 - 15:45  |  Author(s): D. Harpole, R. Bueno, W.G. Richards, D. Beer, K.V. Ballman, M.S. Tsao, F.A. Shepard, D.T. Merrick, A. Van Bokhoven, W.A. Franklin, R. Govindan, M. Watson, D.R. Gandara, G. Chen, Z.H. Chen, L. Chirieac, H. Chui, C. Genova, M. Joshi, A. Kowalewski, M. Onaitis, C.J. Rivard, T. Sporn, F.R. Hirsch

      • Abstract

      Background:
      Despite overall favorable prognosis for operable early stage non-small cell lung cancer, predicting outcome for individual patients has remained challenging. Small retrospective studies have reported potential non-coding micro(mi)RNAs that might have prognostic significance; however, these studies lacked statistical power and validation. To refine these initial findings to clinical application, the investigators have undertaken a collaborative, structured evaluation of multiple signatures putatively prognostic for lung squamous cell carcinoma (SCC) under a NCI/SPECS (Strategic Partnerships fo Evaluating Cancer Signatures) award. The study design specifies a primary validation cohort comprising institutional cases, and additional validation cohorts of Cooperative Group cases, all profiled via a common pipeline.

      Methods:
      Completely resected SCC (confirmed by central pathology review) meeting clinical (Stage I-II; complete 3-year follow-up) and specimen quality criteria (Tumor cellularity ≥ 50%;necrosis ≤ 20%) were submitted by 6 institutions. Clinical, pathological and outcome data were uploaded to a central database. Lysates from 5 um sections of FFPE SSC tumor samples were run on the HTG EdgeSeq Processor (HTG Molecular Diagnostics, Tucson, AZ) using the miRNA whole transcriptome assay in which an excess of nuclease protection probes (NPPs) complimentary to each miRNA hybridize to their target. S1 nuclease then removes un-hybridized probes and RNA leaving behind only NPPs hybridized to their targets in a 1-to-1 ratio. Samples were individually barcoded (using a 16-cycle PCR reaction to add adapters and molecular barcodes), individually purified using AMPure XP beads (Beckman Coulter, Brea, CA) and quantitated using a KAPA Library Quantification kit (KAPA Biosystems, Wilmington, MA). Libraries were sequenced on the Illumina HiSeq platform (Illumina, San Diego, CA) for quantification. Standardization and normalization was provided to the project statistical core for validation of two pre-existing signatures and generation of new models (MCP clustering).

      Results:
      Among 224 cases with miRNA data, median age was 70 (43-92), 143 (64%) male, with 67% former (67%) and current (26%) smokers. All patients were completely resected stage I or II. . At follow-up, 59 (26%) had documented recurrence and 129 (58%) were deceased. To date, we have been unable to validate the previous models, but have created a novel signature of three miRNAs (see Figure) that is being validated in the second phase of the project using an independent, blinded multi-institutional cohort.

      Conclusion:
      The Squamous Lung Cancer SPECS Consortium has established well-annotated and quality-controlled resources for validation of prognostic miRNA signatures. A new candidate 3-miRNA signature has been identified for further development as a clinically useful biomarker.

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      P1.05-002 - The Prognostic Impact of EGFR Mutation Status and Mutation Subtypes in Patients with Surgically Resected Lung Adenocarcinomas (ID 3932)

      14:30 - 15:45  |  Author(s): K. Takamochi, S. Oh, T. Matsunaga, K. Suzuki

      • Abstract

      Background:
      EGFR mutation status is a well-established predictor of the efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer. Recently, the differences in EGFR mutation subtypes were also reported to be associated with the efficacy of EGFR TKIs. However, the prognostic impact of EGFR mutation status and mutation subtypes remains controversial.

      Methods:
      We retrospectively reviewed 945 consecutive patients with surgically resected adenocarcinomas who had their EGFR mutation status analyzed between January 2010 and December 2014. Overall survival (OS) and recurrence-free survival (RFS) were analyzed in three cohorts (all patients, pathological stage I patients, and patients with exon 21 L858R point mutation or exon 19 deletions) using Kaplan-Meier methods and Cox regression models.

      Results:
      The median follow-up time was 42 months. The results for EGFR mutation status, mutation subtype, and the comparison data of OS/RFS are summarized in the attached Table. Positive EGFR mutation status was significantly associated with longer OS/RFS in all patients and was also associated with longer OS in pathological stage I patients. However, no significant differences were observed in OS/RFS between patients with exon 21 L858R point mutation and those with exon 19 deletions. In a Cox regression model for OS, the EGFR mutation status was a significant prognostic factor that was independent of well-established prognostic factors such as age, pathological stage, vascular invasion, lymphatic permeation, and serum CEA level.

      3y-RFS 5y-RFS P 3y-OS 5y-OS P
      All Pts 0.009 < 0.001
      EGFR mut+ (N = 423) 84.6% 76.7% 95.2% 89.0%
      EGFR mut- (N = 522) 78.8% 71.2% 84.9% 76.5%
      p stage I Pts 0.102 < 0.001
      EGFR mut+ (N = 352) 93.4% 85.4% 98.2% 94.5%
      EGFR mut- (N = 392) 90.6% 82.8% 92.6% 85.9%
      Subtypes 0.385 0.507
      Ex 21 L858R (N = 224) 84.8% 79.6% 95.2% 90.0%
      Ex 19 del (N = 164) 84.7% 74.3% 97.5% 95.8%


      Conclusion:
      Positive EGFR mutation status is a favorable prognostic factor in patients with surgically resected lung adenocarcinomas. However, EGFR mutation subtypes (exon 21 L858R point mutation or exon 19 deletions) have no prognostic impact.

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      P1.05-003 - Coexpression of CD8a and PD-L1 Frequently Observed in Resected NSCLC Tumors from Smokers (ID 4764)

      14:30 - 15:45  |  Author(s): A. Lisberg, E.B. Garon, R. McKenna, J. Dering, H. Chen, N. Kamranpour, D. Hou, M. Velez, R.B. Cameron, J.M. Lee, S.M. Dubinett, D. Slamon

      • Abstract

      Background:
      With the approval of anti-programmed cell death-1 (PD-1) therapy in advanced non-small cell lung cancer (NSCLC), identifying patients with early stage disease most likely to benefit from therapy has become a priority. It has been hypothesized that patients whose tumors show evidence of PD-1 mediated T cell exhaustion, via the presence of both tumor infiltrating lymphocytes (TILs) and PD-L1 expression, are more likely to respond to anti-PD-1 therapy (Teng et al, 2015). The current study utilized microarray analysis to evaluate the relationship between both clinicopathologic features and overall survival (OS) with tumor microenvironment (TME) composition.

      Methods:
      Gene expression microarray analysis was performed using the Agilent Whole Human Genome 4x44K 2-color platform for 319 NSCLC and 15 normal resection specimens. The reference sample was an equal mixture of 258 of the NSCLC samples. Rosetta Resolver and Statistica 13.0 were used for analysis. Samples with PD-L1 expression levels greater or unchanged from reference level were classified as positive, while those significantly lower [log (ratio)<0 and p<0.01] than the reference were classified as negative. CD8a expression was used as a surrogate for TILs as previously described by Ock et al. (2016), and categorized in the same manner as PD-L1. Relationships between TME composition and clinicopathologic features were evaluated with the chi-square test. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test.

      Results:
      In the 319 NSCLC samples the incidence of a Type I TME (+CD8a/+PD-L1) was 45%, Type II TME (-CD8a/-PD-L1) 12%, Type III (-CD8a/+PD-L1) 25%, and Type IV (+CD8a/-PD-L1) 18%. When assessing for survival, patients with a PD-L1 negative/CD8a positive (Type IV) TME had improved OS compared to patients with PD-L1 negative/CD8a negative (Type II) TME (p=0.02). When assessed for smoking, ever smokers were more likely to evidence a PD-L1 positive/CD8a positive (type I) TME compared to never smokers, 49% vs 32%, while never smokers more frequently evidenced a PD-L1 positive/CD8a negative (Type III ) TME compared to ever smokers, 37% vs 22% (P=0.05). Interestingly, 75% of normal lung samples evidenced a PD-L1 positive/CD8a positive microenvironment.

      Conclusion:
      Evidence of both TILs and PD-L1 expression was observed in the majority of normal lung specimens and also more frequently in tumors from smokers compared to non-smokers. Patients whose tumors showed evidence of CD8a, but not PD-L1, had improved OS compared to patients without evidence of either. Future studies will utilize immunohistochemistry to corroborate these findings and investigate other components of the TME.

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      P1.05-004 - Surfactant Protein C is a Prognostic Marker in Resected Non-Small Cell Lung Cancer (ID 4393)

      14:30 - 15:45  |  Author(s): I. Macía, J. Moya, G. Aiza, R. Ramos, I. Escobar, F. Rivas, A. Ureña, G. Rosado, P. Rodríguez-Taboada, S. Aso, S. Padrones, C. Déniz, E. Nadal, G. Capella

      • Abstract
      • Slides

      Background:
      The lung cancer cells express genes involved in key points of the lung development. The objective of this study was to determine the prognostic value of expression of embryonic markers in tumour tissue samples from patients with surgically-treated non-small cell lung cancer (NSCLC).

      Methods:
      Study based on 129 primary tumour samples from 102 patients with surgically-treated NSCLC (99% R0) and 27 lung samples. Expression of the following markers was evaluated by mRNA RT-qPCR assay: CEACAM5, FGFR2b, FRS2, MYCN, SFTPC, SHH, SHP2, and SOX17 in the tumour and lung samples. Statistical analyses included chi-squared tests, non-parametric tests, Kaplan Meier curves, log-rank and Cox regression tests.

      Results:
      Patients' characteristics were: mean age 67 ± 8 years, squamous carcinoma (49%), adenocarcinoma (43%), pathological staging: I: 56%, II: 32%, III: 11% and IV: 1%. 18% received adjuvant chemotherapy, 1% radiotherapy and 7% both. CEACAM5 and MYCN were overexpressed in tumour samples related to lung samples (p<0,05), FGFR2b showed similar expression and FRS2, SFTPC, SHH, SHP2 and SOX17 were underexpressed (p<0,05). The squamous carcinomas expressed more FGFR2b, FRS2 and SFTPC (p<0,10), while adenocarcinomas expressed more CEACAM5 (p>0,05). Lymph node involvement was associated with SHH underexpression (p<0,05), intratumoral vascular invasion with CEACAM5 or FGFR2b underexpression (p<0,05) and relapse with SHH (p<0,05) or SFTPC (p=0,09) underexpression. Kaplan-Meier curves of SFTPC were plotted in figure 1. Underexpression of SFTPC in the tumour sample was associated with a 7-fold (7.3; 1.3-40.9) greater active risk of recurrence and a nearly 5-fold (4.9; 1.04-23.2) greater risk of death. Underexpression of SHP2 was associated with a shorter disease-free survival interval (DFS) and overall survival (OS) (p=0.055). Overexpression of FGFR2b or SHH was associated with longer DFS and OS (p<0.05; for SHH, p=0.07 for OS). Combining markers did not provide any additional information. Figure 1



      Conclusion:
      Underexpression of SFTPC in tumour samples was independently associated with worse prognosis.

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      P1.05-005 - Programmed Death-Ligand 1 (PD-L1) in Resected Lung Adenocarcinomas (LA) in a University Hospital (ID 6101)

      14:30 - 15:45  |  Author(s): M. Álvarez, S. Vicente, A. Cebollero, I. Pajares, E. Millastre, J. Hernando, T. Puértolas, R. Álvarez, M.Á. Artal Cortés, A. Antón

      • Abstract

      Background:
      The role of monoclonal antibodies inhibiting of the Programmed Death-1 and its ligand (PD-1/ PD-L1) pathway have been described in advanced disease. The knowledge of the role of this pathway in early stages of lung cancer is still limited. We assessed the incidence of PD-L1 expression in tumour cells of samples of resected lung adenocarcinomas and its prognostic role.

      Methods:
      A retrospective analysis of patients (p) with lung adenocarcinomas radically resected at our Institution between 2004 and 2011 has been conducted. PD-L1 was determined by Immunohistochemistry (SP263, Ventana® assay). A cut-off value of 5% of positive tumour cell was chosen.

      Results:
      112 tumours from 107 p were included. Median age was 62 years. 81% were male, 88% had exposure smoking, baseline performance status was 0 – I – II (62,5% - 26,8% - 10,7%) and pathological stage was I – II – III – IV (49,1% - 26,8% - 23,2% - 0,9%). Fourteen p (12%) expressed PD-L1>5%. They were mostly male (71%), smokers (93%), baseline performance status was 0 – 1 – 2 (64% - 29% - 7%), the most common histological subtype was poorly differentiated adenocarcinoma (64%) and pathological stage was I – II – III (28% - 21% - 50%). One p (7,7%) harboured EGFR mutation, none (0%) were ALK positive and 6 p (46,2%) had a K-RAS mutation. With a follow-up of 52 months median disease free survival (DFS) was 49 months and overall survival (OS) 58 months. Median DFS was shorter in p with expression of PD-L1 (27 months) that in negative tumours (49 months) (p=0,45). Median OS showed a similar pattern (32 vs 66 months respectively) also favouring PD-L1 negative p (p=0,05).

      Conclusion:
      In our series, patients with resected adenocarcinomas expressing PD-L1 in >5% of cells showed a worse disease free and overall survival than patients without such expression.

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      P1.05-006 - Identification of miRNAs and mRNAs Associated with Metastasis in Early-Stage Non-Small Cell Lung Cancer (NSCLC) (ID 5829)

      14:30 - 15:45  |  Author(s): S. Tam, N. Pham, S. Sakashita, E. Kaufman, M. Pintilie, N. Liu, G. Liu, F. Shepherd, M.S. Tsao

      • Abstract

      Background:
      Early-stage NSCLC patients whose tumours can form primary xenografts (XG) in immune deficient mice have significantly shorter disease-free survival and are at a greater risk of early metastasis compared with patients whose tumours do not form xenografts (non-XG). Genomic and proteomic characterization of XG and non-XG-forming primary patient tumours may reveal clinically relevant genetic aberrations that are associated with early metastasis.

      Methods:
      miRNA-seq and RNA-seq data of 100 early-stage NSCLC patients with known engraftment status were acquired. The cohort includes 62% adenocarcinoma (ADC) and 38% squamous cell carcinoma (SQCC). Least absolute shrinkage and selection operator (LASSO) was applied to identify features associated with XG status using integrated miRNA and mRNA abundance profiles. Gene Ontology (GO) annotation was subsequently performed to elucidate biological processes that may be altered between the two patient groups.

      Results:
      Using miRNA and mRNA data alone, ADC patients were classified as XG and non-XG with 88.7% and 95.2% accuracy. The integration of these two data types classified the patients with 100% accuracy using 20 features (7 miRNAs and 13 mRNAs). While less is known regarding the roles of the identified miRNAs in lung ADC, several of the genes have been suggested to affect the metastatic ability of lung cancer cells; these include PITX1, GPNMB and KRT14. In SQCC, both the miRNA and mRNA data alone and the integrated profiles were able to classify patients into XG and non-XG-forming groups with 100% accuracy. However, the roles of the selected features (1 miRNA and 11 mRNAs) in the metastasis of SQCC are not well defined. GO annotation of the identified mRNAs in ADC revealed enrichment of biological processes related to B cell differentiation, wound healing and regulation of the immune response and signalling pathway, while catabolic and metabolic processes were enriched in SQ.

      Conclusion:
      The use of single-dimensional data to classify patients into different prognostic groups may not be sufficient in the presence of heterogeneous patient populations. Integrative analysis of multi-omic data can provide greater insights into clinically relevant genetic aberrations, which can be used to improve the molecular classification of NSCLC.

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      P1.05-007 - Analysis of RNA Sequencing Data along with PET SUV-max Can Discover Novel Gene Sets Which Can Predict Surgical Outcome of NSCLC (ID 5404)

      14:30 - 15:45  |  Author(s): Y. Hwang, Y.J. Jung, S.B. Lee, Y.H. Kim, K. Hyun, S. Park, H.J. Lee, I.K. Park, C.H. Kang, Y.T. Kim

      • Abstract
      • Slides

      Background:
      Recent development of NGS technology provides a better understanding on the molecular mechanism of the cancer. A comprehensive analysis algorism of NGS data along with various clinical phenotypes and clinical outcome may lead discovery of novel molecular mechanism of cancer biology. It has been suggested that the preoperative SUV of the PET-CT is related to the aggressiveness of the cancer. We hypothesized that the identification of genes that were related to the PET SUV-max would lead a discovery of novel genes which could predict long-term outcomes of patients of non-small cell lung cancer.

      Methods:
      We set a 51 adenocarcinoma and a 101 squamous cell carcinoma patients cohort, whose cancer and normal tissue whole transcriptome sequencing data were available. The RNA sequencing fastq files were aligned on the reference genome (http://grch37.ensembl.org/) and the differential expressions were analyzed using tuxedo protocol (TopHat 2.0, Cufflinks 2.2.1). Visualizations of differential expressions were presented with CummeRbund R-package.

      Results:
      Based on the preoperative PET-CT SUV-max, patients were classified as "Low" (SUV≤3), "Intermediate" (SUV 3-10), and "High" (SUV>10) groups. Using the tuxedo RNA analysis tools, we selected 31 genes which showed significantly different expression of RNAs between "Low" and "High" groups in adenocarcinoma and between “Intermediate” and “High” groups in squamous cell carcinoma. By comparing expression levels of those 31 genes according to the development of recurrence, we could identify two sets of genes (COL2A1, BPIFB2, RYR2, F7, HPX, AC022596.6 and H19 for adenocarcinoma; BPIFB2, AC022596.6, ANKRD18B, GCLC, HHIPL2, COL2A1 and DPP10 for squamous cell carcinoma) which were related to the development of recurrence. Figure 1



      Conclusion:
      Our results suggest that it is necessary to set a comprehensive analysis algorithm of the NGS data along with various clinical phenotypes of the patients, for the discovery of clinically meaningful molecular mechanisms of the cancer.

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      P1.05-008 - Detection of EGFR Mutations in Pulmonary Vein and Peripheral Blood Plasma Cell-Free DNA for Analysis of Surgical Treatment in Early-Stage NSCLC (ID 4372)

      14:30 - 15:45  |  Author(s): C. Yang, D. Yang, B. Dong, X. Meng, Y. Liu

      • Abstract

      Background:
      Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. Use of blood plasma cfDNA to detect mutations has spread widely as a form of liquid biopsy. However, it remains unclear which types of samples are appropriate for detecting tumor cell-free DNA in these biopsies. We compared the abundance of EGFR mutations in peripheral blood and pulmonary vein plasma cell-free DNA from patients with early-stage NSCLC.

      Methods:
      In this study, primary lung tumors and matched presurgery peripheral blood plasma samples and intraoperative pulmonary vein blood samples were collected from patients with early-stage NSCLC (n=89). We detected EGFR mutations (exon19 deletion, L858R, G719X, S768I and T790M) in 89 early-stage lung cancer samples using droplet digital PCR (ddPCR) and amplification refractory mutation system (ARMS). EGFR mutation abundance was determined and analyzed to reveal potential impact of samples types.

      Results:
      Presurgery peripheral blood plasma samples (n=89) and intraoperative pulmonary vein blood samples (n=89) matched tumor tissue samples (n=89) were analyzed for EGFR mutations using ddPCR and ARMS respectively. Of the 41 EGFR mutations detected in tumor tissues by ARMS, 37 of the corresponding mutations were detected in presurgical peripheral blood plasma cfDNA and intraoperative pulmonary vein cfDNA , whereas 4 mutations were found in plasma from patients with EGFR wild-type tumors (sensitivity 80.49%, specificity 91.67%).Free circulating DNA was identified in the plasma of pulmonary venous blood and peripheral blood in thirty-seven patients. Of the 37 cases of EGFR mutation positive plasma samples, ddPCR identified a higher mutation abundance of pulmonary venous samples than peripheral blood (1.05% vs. 0.12%, p = 0.007).

      Conclusion:
      This study demonstrates accurate mutation detection in plasma using ddPCR, and that cfDNA can be detected in presurgical peripheral blood and intraoperative pulmonary vein in patients with early-stage lung cancer. Our results suggest that pulmonary venous blood can be obtained from the resected specimen, thus facilitating the detection of cfDNA. Future studies can now address whether monitoring the change of EGFR mutation abundance after surgery identifies patients at risk for recurrence, which could guide therapy decisions for individual NSCLC patients.

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      P1.05-009 - Clinical Value of Circulating Tumor Cell in the Differential Diagnosis of Solitary Pulmonary Nodule (ID 4977)

      14:30 - 15:45  |  Author(s): L. Wang, L. Qiao, W. Yu, J. Lou

      • Abstract
      • Slides

      Background:
      The diagnosis of lung cancer suffers from the lack of accurate, noninvasive and early diagnostic tests. Low-dose helical computed tomography (LDCT) identifies millions of solitary pulmonary nodules (SPN) annually, many of which are undiagnosed as either malignant or benign. When removed surgically, 18%-25% of the nodules are benign, which leads to unnecessary treatment procedures for surgeons, stress and panic for patients and waste of medical resources for government. Therefore, an accurate noninvasive test that can discriminate benign SPN from malignant is urgently needed. Circulating tumor cells (CTCs) are cells shed from either primary or secondary tumors that migrate into the circulatory system and exist at the early stage of cancer. In recent years, CTC has become the research hotspot because of its great significance in the early diagnosis of cancer, disease monitoring, prognosis evaluation and guiding individualized treatment. In this study, we evaluated the application value of CTC in the differential diagnosis of SPN.

      Methods:
      Peripheral blood samples were collected from 134 patients with solitary pulmonary nodule in Shanghai Chest Hospital from September 2013 to January 2015, including 80 patients with malignant nodule and 54 with benign nodule. CTC levels of the above subjects were detected by LT-PCR (ligand-targeted polymerase chain reaction, LT-PCR) assay, and serum CEA and CYFRA21-1 were detected by flow fluorescence assay.

      Results:
      The CTC levels of malignant SPN patients were significantly higher than that of benign SPN patients (P<0.001). The area under the Receiver Operating Characteristic (ROC) curves of CTC and CEA were 0.817(95% CI: 0.743~0.891) and 0.613(95% CI: 0.508~0.718) respectively, while the CYFRA21-1 had no significant meaning in the differential diagnosis of SPN. The positive and negative predictive value (PPV and NPV) in differential diagnosis of SPN for CTC were 89% and 74%. Then the patients were divided into three groups according to the nodule diameter to evaluate the diagnostic value of CTC in SPN with different size. For SPN with diameter less than 8 mm, the PPV and NPV of CTC were 86% and 57%; For SPN with diameter between 8 mm and 20 mm, the PPV and NPV of CTC were 88% and 81%; For SPN with diameter greater than 20 mm, the PPV and NPV of CTC were 92% and 68%.

      Conclusion:
      Compared with traditional tumor marker, CTC detection could provide more clinical value in differential diagnosis of solitary pulmonary nodule.

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      P1.05-010 - Aberrant Promoter Methylation of ESR1 and CDH13 Gene Are an Independent Prognostic Marker in Surgically Resected Non-Small Cell Lung Cancer (ID 3840)

      14:30 - 15:45  |  Author(s): M. Kontic, D. Jovanovic, S. Bojic, H. Nelson, S. Ognjanovic

      • Abstract
      • Slides

      Background:
      Aberrant promoter hypermethylation of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine the correlation between the aberrant promoter methylation of multiple genes and 5-year survival rate in patients with nonsmall cell lung carcinoma (NSCLC) after a surgical resection.

      Methods:
      Primary tumor samples (n=65) and corresponding nonmalignant lung tissues (n=65) were obtained from NSCLC patients who underwent curative surgery. The methylation status of seven genes (SOX1, RASSF1A, HOXA9, CDH13, MGMT, ESR1 i DAPK) was quantified using bisulfite pyrosequencing. Cox proportional hazards models were used to analyze the associations between gene methylation status and overall patient survival.

      Results:
      In the Cox proportional hazards model, ESR1 methylation in tumor tissue was associated with significantly poorer survival, with hazard ratio of 1.09 (95% confidence interval 1.02-1.16, p=0.01). This effect was independent of TNM stage, which was also a predictor of survival. We also found that aberrant methylation in CDH13 gene in tumor tissue was associated with inferior survival in surgically resected NSCLC pateints. In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested.

      Conclusion:
      Our study shows that aberrant promoter methylation of ESR1 and CDH13 genes may be associated with inferior survival, showing promise as a useful prognostic biomarker in patients with NSCLC.

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      P1.05-011 - Comparative Analysis of TTF-1 Copy Number Alterations and Protein Expression in Patients with Non-Small Cell Lung Cancer (ID 5133)

      14:30 - 15:45  |  Author(s): K. Yoshimura, Y. Inoue, N. Kurabe, T. Kahyo, A. Kawase, M. Tanahashi, H. Ogawa, N. Inui, K. Funai, K. Shinmura, H. Niwa, T. Suda, H. Sugimura

      • Abstract
      • Slides

      Background:
      TTF-1 (also known as NKX2-1) is located at chromosome 14q13.3. TTF-1 is a master regulator for the development of normal lung, and is also both a lineage oncogene and a suppressor gene in non-small cell lung cancer (NSCLC). TTF-1 expression is associated with a favorable prognosis. In contrast, the clinical significance of increased TTF-1 gene dosage has yet to be fully elucidated. We explored the relationship of TTF-1 copy number alterations with TTF-1 protein expression as well as patients’ prognoses in a relatively large cohort.

      Methods:
      We assessed TTF-1 gene copy number and protein expression in microarrayed 636 NSCLC, including 421 adenocarcinomas and 173 squamous cell carcinomas (SCCs), and 42 other histologies, using fluorescent in situ hybridization and immunohistochemistry. TTF-1 copy number alterations were divided into three categories; amplification (TTF-1/CEP14 ≥2), polysomy (TTF-1/CEP14 <2 and TTF-1 signals ≥4 copies per nucleus), and disomy (the others). Their associations with clinical data were retrospectively analyzed.

      Results:
      Among the entire cohort, TTF-1 amplification and polysomy were observed in 5.6% (36/636) and 8.3% (53/636), respectively. Tumors with copy number alterations (amplification and polysomy) were detected in 14.5% (61/421) among adenocarcinomas, 9.3% (17/173) among squamous cell carcinomas, and 26.2% (11/42) among other histologies (P = 0.012). TTF-1 expression was almost exclusively observed in adenocarcinomas (P < 0.001). In the adenocarcinoma cohort, the frequency was 6.7% (28/421) for TTF-1 amplification and 7.8% (33/421) for polysomy. TTF-1 positivity was 84.8% (357/421). A multivariate Cox hazards model analysis demonstrated that TTF-1 amplification was an independent worse prognostic factor (hazard ratio (HR), 3.84; 95% confidence interval (CI), 2.18-6.71) for overall survival, but TTF-1 expression was adversely an independent better prognostic factor (HR, 0.49; 95% CI, 0.28-0.85). In the SCC cohort, there were few cases of TTF-1 amplification (1.7%, 3/173), polysomy (8.1%, 14/173), and TTF-1 expression (3.7%, 10/273). Interestingly, any case of adenocarcinoma and SCC with TTF-1 amplification harbored positive TTF-1 expression.

      Conclusion:
      Both TTF-1 amplification and TTF-1 expression were more common in adenocarcinoma. However, they had distinct prognostic roles: TTF-1 amplification was an independent poor prognostic factor in adenocarcinoma, whereas TTF-1 expression was a favorable prognostic factor.

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      P1.05-012 - The Impact of EGFR Mutations on the Prognosis of Patients with Resected Stage I Lung Adenocarcinoma (ID 4753)

      14:30 - 15:45  |  Author(s): J. Kitamura, L.F. Tapias, D.J. Mathisen, M. Lanuti

      • Abstract
      • Slides

      Background:
      Recent studies have reported that epidermal growth factor receptor (EGFR) mutations are potential predictive factors for prognosis as well as for the response to the treatment of EGFR tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma. However, the prognostic role of EGFR mutations has not been well studied in treatment-naïve stage I lung adenocarcinoma. In this study, we evaluated the pure prognostic value of EGFR mutations in patients with stage I lung adenocarcinoma who underwent complete resection.

      Methods:
      We retrospectively reviewed the medical records of treatment-naïve patients who underwent complete resection of stage I lung adenocarcinoma between January 2008 and December 2014. Mutation testing was performed on resected tumor using multiplex (SNaP Shot) polymerase chain reaction assay. Survival curves were generated with Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used for multivariate analysis.

      Results:
      Of 583 patients, 127 (21.8%) patients had EGFR-mutations. Median follow up period after surgery was 36.9 months (range: 0.1-95.8). Patients with EGFR mutations showed a better 5-year recurrence-free survival (RFS, 89.4% vs 77.8%, p=0.0053) and 5-year overall survival (OS, 99.1% vs 87.7%, p=0.0044) than those with EGFR wild-type (Figure). Multivariate analysis demonstrated that the presence of EGFR mutation (HR=0.4875, p=0.0388) and pathological stage 0 or IA (HR=0.4590, p=0.0016) were independent prognostic factors for better RFS. The presence of EGFR mutations (HR=0.1878, p=0.0443), lobar resection (HR=0.4076, p=0.0123), and ECOG performance status 0 (HR=0.4061, p=0.0259) were independent prognostic factors for better OS. Figure 1



      Conclusion:
      Patients harboring an EGFR-mutation in completely resected stage I lung adenocarcinoma had a much improved prognosis compared to those patients whose tumors expressed EGFR wild-type. The presence of an EGFR mutation was a significant positive prognostic factor in this cohort.

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      P1.05-013 - Lung Tumorspheres as a Platform for Testing New Therapeutic Strategies in Non-Small Cell Lung Cancer (ID 4848)

      14:30 - 15:45  |  Author(s): E. Munera Maravilla, A. Herreros Pomares, S. Calabuig Fariñas, E. Escorihuela, E. Duréndez, A.I. Martinez, M. Martorell, A. Blasco, E. Jantus-Lewintre, C. Camps

      • Abstract

      Background:
      Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be linked to a subpopulation known as Cancer Stem Cells (CSCs), which are able to grow as spheroids (suspension culture). The aim of the study was to obtain tumorspheres from lung cancer cell lines and to use them as an in vitro platform for drug screening.

      Methods:
      Cells from lung cancer cell lines (A549, H1650, PC9, H460 and H358) were grown in monolayer and as spheroids. Cultured cells were used: (i) to compare the cytotoxic effect of anticancer drugs in adherent vs lung-tumorspheres (ii) to perform a high-throughput screening with a commercial chemical library (Prestwick) and (iii) to analyze the citotoxicity of specific inhibitors of Wnt, Hedgehog and Notch pathways. Briefly, cells were plated at the desired density in 200 μl of medium in 96-well plates and compounds were added at 4 different concentrations (n=3). Cell viability was measured after 48 and 72h, using MTS Assay. Cell viability was normalized to the respective mock-treated control cells and presented as percentage of control.

      Results:
      Cells cultured in serum-free conditions were able to form spheroids, such as stem-like cells. Under these culture conditions, classical anticancer drugs (cisplatin, paclitaxel, vinorelbine and pemetrexed) exhibited mild or null cytotoxic effects on A549, H1650, PC9, H460 and H358 spheroids. Moreover, we performed a high-throughput screening with Prestwick library and remarkably, three compounds reduced the number of viable cancer cells. As regards ‘stemness’ inhibitors, Wnt (IWP2 and XAV939) and Hedgehog inhibitors (Vismodegib) show high activity against tumorspheres (p<0.05), suggesting them as possible therapeutic strategies in NSCLC

      Conclusion:
      Our data suggest that lung-tumorspheres showed resistance to classical anticancer drugs, strengthening its possible use as a short-term culture platform for a simple, and cost- effective screening to investigate novel therapeutic approaches. In this setting, some compounds were identified as promising therapeutic agents on lung tumorspheres, but confirmatory data are still necessary. This project was supported by [RD12/0036/0025] from RTICC, SEOM 2012, [PI12-02838 and PI15-00753] from ISCIII

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      P1.05-014 - Stemness Gene Expression Profile of Tumorspheres from Non-Small Cell Lung Cancer (ID 4748)

      14:30 - 15:45  |  Author(s): A. Herreros Pomares, S. Calabuig Fariñas, E. Munera Maravilla, A. Blasco, A.I. Martinez, E. García Del Olmo, E. Jantus-Lewintre, C. Camps

      • Abstract

      Background:
      Lung cancer features like chemoresistance, tumor progression or metastasis have consolidated lung cancer as the first cause of death cancer-related worldwide. Cancer stem cells (CSCs) are small subpopulations of stem-like cells that have been associated to these traits, constituting a promising target, but remaining largely unknown. In this study, we isolated CSCs from lung cancer cell lines and tumor tissue of resectable NSCLC patients using a sphere-forming assay and analyzed their gene expression profile.

      Methods:
      The investigation was carried out on cells from seven NSCLC tumor samples and six cell lines (H1650, H1993, H358, A549, PC9, H460) grown in monolayer and as spheroids. The expression of CSC-markers (CD133, EPCAM1, ALDH1A1, CD166, ABCG2, CD44, MUC1, BMI1, THY1), pluripotency promoters (KLF4, OCT4, NANOG, SOX2, MYC, CCND1), cell cycle regulators (CDKN1A, CDKN2A, MDM2, WEE1), invasiveness-related genes (CDH1, VIM, SNAI1, MMP2, MMP9, CEACAM5, ITGA2, ITGA6, ITGB1), Notch pathway (NOTCH1, NOTCH2, NOTCH3, JAG1, DLL1, DLL4, NUMB, HEY1, HES1), Wnt pathway (WNT1, WNT2, WNT3, WNT5A, CTNBB1, DKK1, FZD7) and Hedgehog pathway (SMO, PTCH1, SHH, GLI1) components were analyzed by quantitative real time PCR (RTqPCR). ACTB, CDKN1B and GUSB genes were used as housekeeping controls for the relative expression calculation.

      Results:
      Lungspheres showed significantly higher expression of the CSC-markers EPCAM1, CD44 and ALDH1A1 (p= 0.028, p= 0.021 and p= 0.043, respectively) and the quiescence promoter CDKN1A (p= 0.021) in comparison with their paired-monolayer cells. The epithelial to mesenquimal transition (EMT) inducer, SNAI1, as well as integrins ITGA2, ITGA6 and ITGB1 were overexpressed in tumorspheres (p= 0.011, p= 0.018, p= 0.016 and p= 0.013, respectively). Regarding the Notch signaling pathway, most ligands (JAG1 and DLL4) and receptors (NOTCH1 and NOTCH2) analyzed had increased expression in spheroids (p= 0.021, p= 0.028, p= 0.038 and p= 0.036, respectively). In Wnt pathway, we found higher expression levels of WNT3, CTNBB1 and GSK3B (p= 0.021, p= 0.008 and p= 0.021, respectively) in tumorspheres. No significant results were found for the rest of genes analyzed.

      Conclusion:
      Lung cancer spheroids from primary tumors and cell lines showed increased levels of genes related to CSCs properties. Genes belonging to Notch and Wnt signaling pathways were found to be more expressed in tumorspheres, suggesting that these pathways could be interesting lung-CSC targets. This work was supported in part, by grants RD12/0036/0025 from RTICC, and PI12-02838/PI15-0753 from ISCIII.

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      P1.05-015 - Genomic Characterisation of Non-Small Cell Lung Cancer in an Australian Population (ID 4052)

      14:30 - 15:45  |  Author(s): B. Parris, D. Irwin, M. Daniels, L. Franz, F. Goh, L. Passmore, E. McCaul, D. Courtney, R. Bowman, I. Yang, K. Fong

      • Abstract

      Background:
      Lung cancer is a heterogeneous disease with poor prognosis. Genomic variants may predict sensitivity to targeted drug therapies or assist in prognostication. We sought to determine the frequency of driver mutations and gene rearrangements in non-small cell lung cancer (NSCLC) and evaluate the feasibility of the MassARRAY system for multiplexed mutational profiling.

      Methods:
      A cohort study of 419 fresh-frozen NSCLC tumours was performed (AC, n=370; SCC, n=39; ASC, n=7; LCC, n=3). High-throughput and multiplexed mutational profiling was performed using the MassARRAY genotyping system (Agena Bioscience) (n=419). The OncoFOCUS+KIT panel was used for detecting genomic variants in EGFR, BRAF, KRAS, NRAS and KIT (n=413) and the LungFusion panel for fusion genes involving ALK, RET and ROS1 (n=371). Clinico-pathological associations were evaluated using Fisher’s exact test for categorical data, and T test for continuous data. A p-value of <0.05 (two-tailed) was considered statistically significant.

      Results:
      At least one genomic variant was detected in 196 (46.8%) cases (n=419). EGFR mutations were identified in 42 cases (10.2%), KRAS in 133 (32.3%), BRAF in 11 (2.7%), NRAS in 4 (1.0%) and no KIT mutations were detected. Gene rearrangements involving ALK, RET and ROS1 were identified in 2 (0.5%), 1 (0.3%) and 5 (1.3%) cases respectively. Based on current clinical guidelines for NSCLC, 28 patients would qualify for tyrosine kinase inhibitor therapy, and 4 for targeted therapy available for other cancers (BRAF V600E). EGFR mutations were significantly associated with adenocarcinoma histology and female never smokers (p<0.001) and KRAS mutations predominated in smokers (p<0.001).

      Conclusion:
      Driver mutations were detected in 46.8% of NSCLC cases resected at TPCH. Rapid, multiplexed mutation testing can guide treatment as well as assist in patient stratification for clinical trials.

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      P1.05-016 - Circulating BARD1 Antibodies for Early Detection of Lung Cancer (ID 4193)

      14:30 - 15:45  |  Author(s): I. Irminger-Finger, M. Pilyugin, A. Bianco, B. Hegedus, S. Sardy, P. Descloux, G. Laurent

      • Abstract

      Background:
      In a study of more than 100 NSCLC cases we previously showed that the expression of BARD1 isoforms is correlated with poor patient survival. BARD1 is a tumor suppressor acting with BRCA1 as ubiquitin ligase. BARD1 has also functions in mitosis and poly(ADP)-ribose signaling for DNA repair. In cancer cells BARD1 isoforms are generated by alternative splicing. SNP affecting splicing and cancer predisposition were identified in neuroblastoma. The alternatively spliced isoforms lack tumor suppressor functions and act as oncogenes. As the domain composition of cancer-associated isoforms predicts altered tertiary structures, we investigated whether BARD1 isoforms act as cancer antigens.

      Methods:
      ELISA assays were performed to detect antibodies generated against BARD1 isoforms in the serum of lung cancer patients. We used BARD1 protein fragments and short peptides for capturing autoimmune antibodies. Using fitted Lasso logistic regression methods, we developed an algorithm for the prediction of lung cancer based on a blood test for detection of BARD1 antibodies.

      Results:
      Modeling values from 200 samples, shows a distinction of lung cancer and healthy controls with high sensitivity and specificity (AUC=0.961; Figure 1). Splitting the samples randomly and repeatedly into training sets and validation sets, confirmed an average AUC=0.964 for the training sets and AUC=0.861 for the validation sets. ROC curves for early and late stage lung cancers showed no difference in their AUCs. The BARD1 lung cancer test is highly specific and does not cross-react with other cancers.

      Conclusion:
      Lung cancer has a very long latent phase and is often discovered at an advanced and untreatable stage. Currently the detection by low dose CT scan is relatively expensive and not very specific. Therefore a blood test, such as the BARD1 test could i) help to detect cancers earlier, in particular by screening of risk groups, and ii) become a diagnostic aid in combination with CT scan.Figure 1



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      P1.05-017 - The Prognostic Impact of EGFR, KRAS and TP53 Somatic Mutations in Curatively Resected Early-Stage Lung Adenocarcinomas (ID 4527)

      14:30 - 15:45  |  Author(s): B.E. Gould Rothberg, R. Das, L.K. Jackson, H. Lazowski, Y. Bai, D. O'Neill, S.H. Roberts, J.M. Rothberg, R. Herbst, A.W. Kim, D. Boffa, D. Rimm, F. Detterbeck, L.T. Tanoue

      • Abstract

      Background:
      As the 5-year survival among individuals undergoing curative-intent resection for early-stage lung cancer approaches 50%, identification of prognostic biomarkers useful for risk stratification is a priority. While somatic mutation profiling drives treatment choice in advanced disease, its usefulness among early-stage patients is not well-established.

      Methods:
      From May 2011 through December 2014, The Yale Lung Cancer Biorepository enrolled 192 individuals who underwent curative-intent complete resection for Stage IA-IIIA adenocarcinoma. Demographics and lifestyle choices were ascertained by interview using validated questionnaires. Pathologic characterization of index tumors, including CLIA Laboratory-assayed EGFR/KRAS status, was extracted from the medical record. A custom targeted resequencing panel covering all coding exons from 93 lung adenocarcinoma-related genes was designed. Buffy coat-derived germline DNA and tumor DNA, extracted from the FFPE surgical specimen, were sequenced on the Ion Torrent platform with >90% of the assayed amplicons achieving >30x coverage in both tumor and germline from each case. Somatic nonsynonymous tumor variants were identified using the Torrent Variant Caller. Bivariate associations were evaluated by Chi-square or ANOVA. Survival analyses were conducted using Cox modeling.

      Results:
      181/192 (94.3%) participants underwent EGFR/KRAS somatic mutation profiling with 43 EGFR mutations and 71 KRAS mutations detected. EGFR mutations were more common among well- and moderately-differentiated lesions (p=0.06) and among never or former light smokers (p=0.0007). Seventy-two percent of EGFR and 81.7% of KRAS mutations were found among female patients (p=0.0008). The joint distribution between smoking and gender favored EGFR mutations among female never/former smokers, KRAS mutations among female ever-smokers and EGFR/KRAS wild-type status among male ever-smokers (p=0.0002). After adjustment for AJCC 7[th] edition Tstage, Nstage and presence of lymphovascular invasion, KRAS mutations (HR=2.14; 95% CI:1.04-4.43; p=0.04) but not EGFR mutations (p=0.63) were prognostic for poorer disease-free survival. Targeted resequencing data is available on 148 cases. The nonsynonymous mutation burden ranged from 0-7 with 84% of cases having ≤3. In addition to KRAS and EGFR, frequent mutations were noted in p53 (n=40; 27.0%), STK11 (n=10; 6.8%) and PIK3CA (n=7; 4.7%) with 4 genes mutated in 6 cases. TP53 mutations were associated with high nonsynonymous mutation burden (p<0.0001) and the joint distribution with EGFR/KRAS status revealed the highest burden among KRAS[mut]/TP53[mut] (3.94±1.57) followed by EGFR[mut]/TP53[mut] (3.07±1.61) and EGFR_KRAS[wt]/TP53[mut] (2.20±1.40; p<0.0001).

      Conclusion:
      KRAS[mut], like EGFR[mut], is associated with female gender but only KRAS[mut] is prognostic following curative-intent resection. Elevated mutation burden observed among KRAS[mut]/TP53[mut] may offer novel therapeutic options following recurrence.

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      P1.05-018 - LncRNA16 is a Potential Biomarker for Early-Stage Lung Cancer That Promotes Cell Proliferation by Regulating the Cell Cycle (ID 4693)

      14:30 - 15:45  |  Author(s): N. Wu, H. Zhu, L. Zhang, Y. Yang, X. Wang

      • Abstract
      • Slides

      Background:
      Early diagnosis of lung cancer greatly reduces mortality; however, the lack of suitable plasma biomarkers presents a major obstacle. Recent studies showed that long noncoding RNAs (lncRNAs) play important roles in cancer initiation and development.

      Methods:
      Here, we identify differential expressed lncRNAs by using custom designed microarray on 20 lung cancer samples and evaluate the expression by Real-time PCR (qRT-PCR) on 118 lung cancer samples.The role of lncRNA16 in lung cancer was studied in vitro and in vivo, utilizing the lung cancer cell line PC9 ,A549 and xenograft mouse models.

      Results:
      lncRNA16 (ENST00000539303) expression level was highly in lung cancer (80/118) and in plasma (32/42) of lung cancer patients. In early stage, lncRNA16 expression levels were significantly higher compare to that in adjacent matched normal tissues (Figure 1C-1F) . Importantly, this increase was mirrored in plasma samples of early stage lung cancer patients (Figure 2A) . Our study reveals that knockdown of lncRNA16 inhibited proliferation of PC9 cells in vitro and also inhibited tumor growth in xenograft mouse models. Specifically, we show that lncRNA16 promotes G2/M transition through regulating cyclin B1 transcription.

      Conclusion:
      In conclusion, lncRNA16 was identified as a potential biomarker for lung cancer diagnosis, as it displayed significantly elevated levels in cancer patient over baseline. Furthermore, we showed that the false-negative rate is significantly lower compared to markers those widely used for lung cancer assessment.

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      P1.05-019 - Two Inflammatory Biomarkers MDC/CCL22 and BLC/CXCL13 Are Independently Associated with the Significant Risk of Early Stage Lung Adenocarcinoma (ID 3966)

      14:30 - 15:45  |  Author(s): Y. Zhang, K. Yu, S. Hu, Y. Lou, C. Liu, J. Xu, R. Li, X. Zhang, H. Wang, B. Han

      • Abstract
      • Slides

      Background:
      This prospective study was designed to investigate the association between multiple inflammatory biomarkers in circulation and the risk for early stage lung adenocarcinoma.

      Methods:
      We measured 10 inflammatory biomarkers in 228 early stage lung adenocarcinoma patients and 228 age, sex and smoking matched healthy controls by using the Luminex bead-based assay.

      Results:
      Only two biomarkers were significantly associated with early stage lung adenocarcinoma risk after Bonferroni correction: the multivariate odd ratio or OR (95% confidence interval or CI) was 0.29 (0.16-0.53) for MDC/CCL22 (P<0.0001) and 4.17 (2.23-7.79) for BLC /CXCL13 (P<0.0001) for the comparison of 4[th] quartile with 1[st] quartile. When analysis was restricted to never smokers (196 patients/196 controls), MDC/CCL22 and BLC/CXCL13 were still significantly associated with early stage lung adenocarcinoma risk (OR; 95% CI; P: 0.37; 0.21-0.66; P<0.0001 for MDC/CCL22 and 2.78; 1.48-5.22; P =0.001 for BLC/CXCL13). Additionally, significance persisted after restricting analysis to 159 stage IA lung adenocarcinoma patients and 159 matched controls for MDC/CCL22 (OR; 95% CI; P: 0.37; 0.21-0.66; <0.0001) and BLC/CXCL13 (2.78; 1.48-5.22). Furthermore, elevated BLC/CXCL13 was associated with a 2.90-fold (95% CI: 1.03-8.17; P=0.037) increased risk of subcentimeter lung adenocarcinoma, and there was an increasing trend for BLC/CXCL13 with the progression of subcentimeter lung adenocarcinoma.

      Conclusion:
      Our findings demonstrated that MDC/CCL22 and BLC/CXCL13 were independently associated with the significant risk of early stage lung adenocarcinoma, and this association persisted even in non-smokers and in stage IA patients. Moreover, BLC/CXCL13 was identified to play a carcinogenic role in the progression of lung adenocarcinoma.

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      P1.05-020 - Opposing Prognostic Roles of CD73 and A2A Adenosine Receptor in Non-Small-Cell Lung Cancer (ID 5139)

      14:30 - 15:45  |  Author(s): Y. Inoue, K. Yoshimura, N. Kurabe, T. Kahyo, A. Kawase, M. Tanahashi, H. Ogawa, N. Inui, K. Funai, K. Shinmura, H. Niwa, T. Suda, H. Sugimura

      • Abstract
      • Slides

      Background:
      CD73 (otherwise known as ecto-5’-nucleotidase) is an important molecule in the adenosine pathway because it generates adenosine by enzymatically dephosphorylating extracellular AMP, which results in immunosuppressed niche within the tumor microenvironment. A2A adenosine receptor (A2AR) acts as a predominant receptor for adenosine in immune cells and can also be expressed in lung tumor cells. However, the clinical impact of the adenosine pathway in non-small-cell lung cancer (NSCLC) has yet to be uncovered, although the pathway has been shown to have a pivotal role in the regulation of anti-tumor immunity and is considered as one of the promising future treatment targets.

      Methods:
      We investigated CD73 and A2AR protein expression profiles using immunohistochemistry in tissue microarrays containing 642 resected NSCLC specimens. The expression levels were assessed using the H-score method that ranged from 0 to 300, and cutoffs were determined using the minimum P-value method for overall survival (OS). The associations between their expression levels and clinicopathological and molecular characteristics as well as patients’ prognoses were retrospectively analyzed.

      Results:
      The median age of patients was 68 years old (range, 23–88) and 440 (68.5%) patients were male. 438 (68.2%) patients had smoking history and 420 (65.4%) patients had adenocarcinoma histology. Significantly higher expression of both CD73 and A2AR was observed in female than male, in never smokers than ever smokers, and in adenocarcinomas than squamous cell carcinomas. Among adenocarcinomas, both high CD73 and A2AR expression were significantly associated with TTF-1 positivity and EGFR mutations. ALK-positive adenocarcinomas showed significantly higher expression levels of CD73 than ALK-negative tumors. High CD73 expression was an independent indicator of a poor prognosis for NSCLC patients in multivariate Cox regression analyses for OS (hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.38–3.47) and disease-specific survival (DSS) (HR, 2.97; 95% CI, 1.78–4.95). Contrary, high A2AR expression was an independent favorable predictor of prognosis for OS (HR, 0.69; 95% CI, 0.49–0.97) and DSS (HR, 0.51; 95% CI, 0.33–0.79). Among adenocarcinomas, high CD73 expression was an independent poor prognostic marker for OS (HR, 2.73; 95% CI, 1.61–4.63) and DSS (HR, 4.57; 95% CI, 2.54–8.23), whereas high A2AR expression was an independent favorable prognostic marker for DSS (HR, 0.56; 95% CI, 0.32–0.98).

      Conclusion:
      Both CD73 and A2AR expression was associated with TTF-1-positive and EGFR-mutant adenocarcinoma. Nonetheless, they had opposing prognostic significance in resected NSCLC.

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      P1.05-021 - circRNAs: Potential Novel Biomarkers for the Early Detection of Lung Cancer (ID 5020)

      14:30 - 15:45  |  Author(s): R. Lin, G. Reid, L. Mutti, A.W. Ryan, S. Nicholson, N. Leonard, V. Young, R. Ryan, S.P. Finn, S. Cuffe, S.G. Gray

      • Abstract

      Background:
      Lung cancer is the leading cancer killer globally. Cancers such as colon, breast, and prostate all have relatively reliable early detection tests. In contrast, lung cancer does not. If caught early, lung cancer has a much better prognosis. Non-invasive or minimally invasive tools to improve early detection of lung cancer represents a critical unmet need. Analysis of the human transcriptome indicates that a mere 2% of the genome corresponds to protein coding transcripts, yet ~ 75% of the genome is transcribed. It is now well established that these non-coding RNAs (ncRNAs) play important regulatory functions within the cell and their expression are often altered in cancer. Circular RNAs (circRNAs) are a species of ncRNAs. They are abundant, conserved and demonstrate cell-type specific expression patterns. Moreover, they are extremely stable with half-life’s greater than 48 hours, are resistant to degradation by RNA exonucleases, and have been shown to play important roles in cancer. Taken together these suggest that circRNAs could potentially be important biomarkers in early lung cancer diagnosis.

      Methods:
      Total RNAs isolated from a panel of matched normal/tumour NSCLC adenocarcinoma (Stage IA/IB) samples (n=6) were probed for circRNAs using the Arraystar circRNA microarray. Survival was assessed on linear mRNAs with associated circRNAs using KM-Plot.

      Results:
      Interim analysis of the data has identified n=206 circRNAs with a 2-fold difference in expression between their matched normal vs. tumour counterparts. Principal Component Analysis (PCA) demonstrated a clear separation of the samples (Tumour vs. Normal). Self-Organizing Maps (SOMs) analysis generated distinctive SOMS clusters of circRNAs, while associated linear pathway enrichment for microRNA and transcriptional binding motifs identified several additional potential networks. Moreover, an analysis of linear mRNAs associated with 10 circRNAs with altered expression in adenocarcinomas found that these mRNAs were linked to overall survival, and that the majority were adenocarcinoma specific.

      Conclusion:
      Altered levels of a number of circRNAs were associated with lung adenocarcinoma. A separate cohort of squamous cell carcinomas is currently being assessed for circRNAs. At present we are validating the expression of these circRNAs in a larger cohort of specimens, and assessing whether or not these are detectable in plasma/serum from the same individuals. Overall, circRNAs may represent novel potential biomarkers for the detection of NSCLC, and may provide additional critical basic knowledge regarding the development and biology of NSCLC.

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      P1.05-022 - Circulating Tumor Cell Isolation to Monitor NSCLC Patients over the Course of Treatment (ID 5975)

      14:30 - 15:45  |  Author(s): J. Herrmann, J. Pfannkuche, T. Lesser

      • Abstract
      • Slides

      Background:
      Compared to the investigation of the primary tumor or a biopsy taken from a distant metastasis, the investigation of a patient’s blood is relatively simple, less invasive and can be performed repeatedly. Thus, CTC (circulating tumor cells) investigation can be used as a real-time marker for staging, disease progression and therapy responsiveness. Cancer mortality might be reduced dramatically when the disease and its metastatic spread are detected and characterized early and can therefore be treated in an optimal fashion. The GILUPI CellCollector[® ]offers medical personnel at any point-of-care with the unique opportunity to enrich these CTCs in vivo. Here, we conducted a study using this effective device, to monitor CTC counts before as well as on different time points after surgery in non-small cell lung cancer (NSCLC) patients and further to characterize the CTCs on a molecular level.

      Methods:
      In total, 20 NSCLC patients (different stages) were screened for CTCs at different time points: preoperative, 30 minutes after tumor resection, 1 week postoperative as well as in 3-monthly intervals up to 2 years. In addition, 1 patient with a benign lung disease were included in this study.

      Results:
      CTCs were isolated independent from tumor stages and even in quite early cases CTCs could be detected. Moreover, a difference between CTC occurrence before and after surgery was seen and a correlation between CTC enumeration and clinical lack of recurrence could be detected.

      Conclusion:
      The GILUPI CellCollector® overcomes blood volume limitations of other diagnostic approaches and thereby increases the diagnostic sensitivity of CTC analysis. Future implementation into clinical practice may improve early detection, prognosis and therapy monitoring of cancer patients. Besides enumeration, captured CTCs are ready for molecular characterization and will help to establish more personalized treatment regiments since knowledge of the molecular make-up of the cancer cells to be defeated is an indispensable prerequisite to use targeted therapies efficiently.

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      P1.05-023 - Induction of Patient-Derived Xenograft Formation and Clinical Significance for PD-L1 in Lung Cancer Patients (ID 4668)

      14:30 - 15:45  |  Author(s): P. Zhang, Y. Ma, J. Si

      • Abstract
      • Slides

      Background:
      The relevance of programmed cell death ligand 1 (PD-L1) to patient-derived xenograft (PDX) formation and clinicopathological characteristics in early stage lung cancer was studied

      Methods:
      Cell counting kit-8 and flow cytometry were carried out to examine proliferation and apoptosis in PC9 and H520 cells transfected with siRNAs. Nod-scid mice were used to establish PDX. Immunohistochemistry was done to investigate PD-L1 expression in tumor tissues.

      Results:
      Proliferation was reduced and apoptosis was induced when PD-L1 was inhibited in the cells. Higher PD-L1 expression rate was observed in the primary tumors with PDX formation than in the tumors without PDX formation. Moreover, PD-L1 was found to be related to smoking, histological types, stages and overall survival in 209 of lung cancer patients.

      Conclusion:
      This study suggests that PD-L1 promotes PDX formation ability and is an independent prognostic marker for the early stage lung cancer patients.

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      P1.05-024 - Preoperative Neuron-Specific Enolase to Albumin Ratio is a Prognostic Biomarker for Patients with Operable Non-Small-Cell Lung Cancer (ID 5273)

      14:30 - 15:45  |  Author(s): H. Ren, X. Li, B. Zhang, Y. Zhang, L. Yang, G. Xiao, X. Gao, G. Huang, P. Wang, H. Wang, C. Yang, S. Qin

      • Abstract
      • Slides

      Background:
      Neuron-specific Enolase (NSE) is a widely used tumor biomarker in small-cell lung cancer (SCLC) diagnosis, and serum albumin (Alb) levels are commonly used as indicators of the nutritional status of cancer patients. However, the prognostic value of these markers in combination has not been examined. This study was designed to explore the value of the combination between NSE and Alb in non-small-cell lung cancer (NSCLC).

      Methods:
      We retrospectively evaluated the prognostic value of the preoperative NSE to albumin ratio (NAR) in 319 patients with operable NSCLC. We analyzed associations among the NAR, clinicopathological characteristics, and inflammatory biomarkers. Univariate and multivariate analyses were performed to identify the clinicopathological characteristics associated with OS. Furthermore, we compared the prognostic value of the NAR with other established prognostic indexes by evaluating the area under the curves (AUC).

      Results:
      The optimal NAR cutoff level was found to be 3.2×10[-7]. We found that a higher NAR was associated with more advanced TNM staged cancers (P=0.041) and higher tumor stage (P=0.011).The NAR was also associated with the inflammatory biomarker albumin/globulin ratio (AGR, P=0.032), but not the neutrophil/lymphocyte ratio (NLR, P=0.295) or platelet/lymphocyte ratio (PLR, P=0.260). In multivariate analyses, the NAR was an independent prognostic factor for NSCLC patients (P<0.001). The AUC of the NAR was higher than the NLR, PLR or AGR at 24 and 36 months of follow-up.

      Conclusion:
      The preoperative NAR might be an independent prognostic factor for patients with operable NSCLC, and a higher NAR indicates a poorer prognosis.

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      P1.05-025 - Prognostic Significance of Hepatitis B Virus to Stage IB Non-Small Cell Lung Cancer Patients in China (ID 5474)

      14:30 - 15:45  |  Author(s): S. Lu, Z. Li

      • Abstract

      Background:
      Hepatitis B virus (HBV) is considered to be a major cause of hepatocellular carcinoma. However, little is known about the role of chronic HBV infection in other malignancies. We aimed to determine HBV infection with other well established prognostic factors and performed multivariate survival analyses to evaluate its value in Chinese non-small cell lung cancer (NSCLC) patients.

      Methods:
      It is a retrospective evaluation of the impact of HBV infection status in 366 patients who underwent complete surgical resection for stage IB NSCLC NSCLC patients in Shanghai Chest Hospital from 1998 to 2008. All the patients were Shanghai Niece and all the stage IB NSCLC patients didn’t receive adjuvant chemotherapy. The patients’ blood samples were tested with chemiluminescent immunoassay for the presence of HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs) before operation. Other variables in the analysis included age, gender, history of smoking and pathologic type. HBsAg positive was definite as HBV infection.

      Results:
      Figure 1 51 HBV infection cases (13.93%) were positive in stage IB NSCLC. The 5-year overall survival of patients without or with chronic HBV infection were 71.25% and 50.98% (P=0.028). Multivariate analyses revealed that gender, chronic HBV infection were significant predictive factors for overall survival (P< 0.05).



      Conclusion:
      The chronic HBV infection is a significant independent prognostic factor in stage IB non-small cell lung cancer.

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      P1.05-026 - High Resolution Metabolomics on Exhaled Breath Condensate to Discover Lung Cancer's Biomarker (ID 5617)

      14:30 - 15:45  |  Author(s): C.Y. Park, A. Khan, A.D. Pamungkas, E.J. Sim, K.H. Kang, S.Y. Lee, Y.H. Park

      • Abstract
      • Slides

      Background:
      Early and non-invasive detection of lung cancer is a desirable prognostic tool for prevention of lung cancer at early stages. Previously, unusual human breath smell of lung cancer patients detected by trained dogs played an important role in early detection of lung cancer. Which suggests that exhaled breath condensate (EBC) is a promising source for searching potential biomarkers in lung cancer patient.

      Methods:
      EBC sample collected using specific device called R-tube, containing both the volatile organic compounds (VOCs) and non-volatile organic compounds (NVOCs), were obtained from patients with lung cancer (n = 20) and control healthy individuals (n = 5). The EBC samples were applied to high resolution metabolomics (HRM) based LC-MS for comparison of metabolic differences among healthy people and lung cancer patients in order to detect potential biomarkers. The multivariate statistical analysis was performed, including a false discovery rate (FDR) of q=0.05, to determine the significant metabolites between the groups. 2-way hierarchical clustering analysis (HCA) was done for determining the classification of significant features between the control healthy and lung cancer patients. The significant features were annotated using Metlin database (metlin.scripps.edu/) and the identified features were then mapped on the human metabolic pathway of the Kyoto Encyclopedia of Genes and Genomes (KEGG). This study was approved by Korea University Guro Hosipital Institutional review board (KUGH14273)

      Results:
      Using metablomics-wide associated study (MWAS), metabolic changes among healthy group and lung cancer patients were determined. The 2-way HCA identified the different metabolic profile in lung cancer patients from healthy control. The identified potential biomarkers are Acetophenone (m/z 103.0542, [M+H-H~2~O][+]), P-tolualdehyde (m/z 138.0914, [M+NH4][+]), 2,4,6-Trichlorophenol (m/z 218.9134, [M+Na][+]) and 11(R)-HETE (m/z 343.2233, [M+Na][+]). The top 5 of affected KEGG pathways are Arachidonic acid metabolism, Glycerophospholipid metabolism, Bile secretion, Inflammatory mediator regulation of TRP channels and Tyrosine metabolism.

      Conclusion:
      Our result shows that Acetophenone, P-tolualdehyde, 2,4,6-Trichlorophenol and 11(R)-HETE are significantly higher in lung cancer patients. Acetophenone and 2,4,6-Trichlorophenol are classified as a Group D human carcinogen approved by US Environmental Protection Agency (EPA), while 11(R)-HETE is associated with Arachidonic acid metabolism and P-tolualdehyde is related to xylene degradation pathway and degradation of aromatic compounds pathway. Our identified metabolites can be the potential biomarkers in EBC for the early and non-invasive detection of lung cancer.

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      P1.05-027 - Novel Prognostic Gene Expression Signatures for Squamous Cell Lung Carcinoma: A Study by the SPECS Lung Consortium (ID 4490)

      14:30 - 15:45  |  Author(s): R. Bueno, W.G. Richards, D. Beer, K.V. Ballman, M.S. Tsao, F.A. Shepard, D.T. Merrick, A. Van Bokhoven, W.A. Franklin, R. Govindan, M. Watson, D.R. Gandara, D. Harpole, Z.H. Chen, G. Chen, L. Chirieac, H. Chui, C. Genova, M. Joshi, A. Kowalewski, M. Onaitis, C.J. Rivard, T. Sporn, F.R. Hirsch

      • Abstract

      Background:
      A multi-institutional squamous lung cancer consortium of investigators is developing prognostic signatures through the US NCI Lung SPECS (Strategic Partnership for Evaluation of Cancer Signatures) program. Six institutions contributed tumor specimens and published/unpublished expression-based prognostic signatures for validation using standardized sample cohorts (a primary validation cohort comprising institutional cases, and additional validation cohorts from two prospective cooperative group studies) and quality controlled assessment in independent laboratory and statistical cores. Here, we report on de novo prognostic signatures derived using the pooled institutional dataset.

      Methods:
      Highly quality-controlled cases of primary SCC from the pooled cohort (N=249) were analyzed to generate de novo prognostic signatures from among the 147 genes comprising pre-existing signatures, and from among all profiled genes. Minimax Concave Penalty (MCP) selection and Ward’s minimum variance clustering yielded survival analyses with 2 clusters that were evaluated using Cox regression and bootstrap cross validation (bCV; 500 iterations).

      Results:
      Two significantly prognostic models were generated (see Figure): Pooled Model A (PMA) was the optimal 2-cluster model using probesets representing 6 genes selected from components of pre-existing signatures: CASP8, MDM2, SEL1L3, RILPL1, LRR1, COPZ2. Pooled Model B (PMB) was the optimal 2-cluster model using probesets representing 6 genes selected from among all those profiled: SSX1, DIAPH3, LOC619427, CASP8, EIF2S1, HSPA13. PMA and PMB each remained independently prognostic in multivariable analyses incorporating an a priori baseline model (age, sex, stage; c-index = 0.641).

      Conclusion:
      Two de novo prognostic signatures were derived using a pooled multi-institutional cohort of SCC assembled for validation of pre-existing signatures. PMA and PMB were each found to be independently prognostic, accounting for established clinical predictors. Both now move forward, along with validated pre-existing signatures, to additional assessment of discrimination, calibration and clinical usefulness using additional independent prospective US co-operative group cohorts of cases. Figure 1



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      P1.05-028 - Phenotypic and Functional Profiling of Tumor-Infiltrating Lymphocytes (TIL) in Early Stage Non-Small Cell Lung Cancer (NSCLC) (ID 6044)

      14:30 - 15:45  |  Author(s): L. Federico, C. Haymaker, M. Forget, L.M. Vence, I. Team, P. Sharma, J. Allison, B. Fang, J. Zhang, H. Wagner, E. Bogatenkova, I. Wistuba, B. Sepesi, J. Heymach, D.L. Gibbons, C. Bernatchez

      • Abstract

      Background:
      The ICON study aims to perform a comprehensive immunogenomic characterization of early stage localized non-small cell lung cancer (NSCLC) and lay the foundation for the identification of barriers to tumor immunity that may be targeted in future trials. Earlier work has demonstrated the prognostic significance of TIL in localized NSCLC. This work evaluates the functional status of T cells infiltrating the NSCLC tumors and their capacity to expand ex-vivo and perform effector function in the first 22 patients enrolled.

      Methods:
      Patients enrolled on the ICON study underwent surgery. Fresh tumor samples were mechanically disaggregated and immediately stained for flow cytometry. Panels consisted of markers of T cell subsets, differentiation status, T cell function, activation and exhaustion. PD-L1 expression was assessed on malignant cells as well as CD68+ tumor-associated macrophages (TAMs) by IHC. Fragments from the tumor tissue were also placed in culture in media containing IL-2 for ex-vivo TIL expansion. TIL cultures were maintained for 3-5 weeks and subsequently underwent phenotypical and functional characterization.

      Results:
      Analysis of freshly disaggregated tumor tissue (n=22) from NSCLC tumor or adjacent normal tissue by flow cytometry demonstrated that effector CD8[+] T cells found in the tumor were less functional than T cells infiltrating normal tissue, revealed by a decrease in the co-expression of the cytotoxic effector molecules perforin and granzyme B (p=0.0004) together with an enhanced expression of the inhibitory receptor PD-1 (p<0.0001). Immunohistochemistry analysis showed PD-L1 expression on malignant cells and/or CD68+ TAMs on all tumor samples except one, strongly suggesting that the PD-1/PD-L1 inhibitory axis was engaged contributing to decreased T cell functionality. TIL could be expanded from the majority of samples (68.2%, n=22). The degree of infiltration predicted the ability to grow TIL ex-vivo (median CD3+ infiltrate of 15.25% of live cells in disaggregated tumor tissue for samples from which TIL could be grown versus 2.9% when TIL could not grow p = 0.015). Immunophenotyping following expansion showed an enrichment in CD8+ aβTCR+ T-cells expressing both perforin and granzyme B indicating that TILs propagated with IL-2 regained functionality (p=0.016). Lastly, NSCLC TIL were rapidly expanded using anti-CD3 antibody, feeder cells and IL-2 over two weeks (n=6) and reached clinically relevant numbers for TIL ACT (range 381-1282 fold expansion).

      Conclusion:
      Overall, while TILs present in NSCLC are functionally inhibited, they can be expanded ex-vivo from most tumor samples and regain a functional phenotype for potential use in adoptive T-cell therapy.

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      P1.05-029 - SABRTOOTH-A Feasibility Study of SABR Compared to Surgery in Patients with Peripheral Stage I NSCLC Considered to Be at Higher Risk from Surgery (ID 4432)

      14:30 - 15:45  |  Author(s): K.N. Franks, M.P. Snee, B. Naidu, D. Sebag-Monterfiore, M. Callister, J. Ferguson, R. Booton, M. Kennedy, C. Lowe, F. Collinson, L. McParland, R. Naylor, J. Webster, W. Gregory, J. Bestall, J. Hewison, D. Baldwin

      • Abstract
      • Slides

      Background:
      Stereotactic Ablative Radiotherapy (SABR) is a well established treatment for medically inoperable peripheral stage I NSCLC. Previous non-randomised evidence supports SABR as an alternative to surgery, but high quality randomised control trial (RCT) evidence is lacking due to low recruitment. The UK SABRtooth study aims to see if a large RCT is feasible.

      Methods:
      The trial management group includes pulmonologists, thoracic surgeons, nurses, patient representatives, oncologists and statisticians. Patients considered at higher-risk of operative mortality and morbidity with a peripheral stage I (<5cm) NSCLC are eligible. Defining “higher-risk” patients considers multiple criteria, but the final decision is left to the individual tumour boards. Equipoise in presenting the two interventions to patients was considered key. Bias is minimised by ensuring the initial approach is by the pulmonologist with subsequent counseling by the research nurse and randomisation occurring before consultation with a surgeon or oncologist . Patients who decline the trial or do not proceed with their allocated treatment are invited to take part in qualitative interviews. The trial is open in 4 thoracic oncology centres and their referral units. The aim is to recruit on average 3 patients/month to demonstrate that a phase III RCT would be feasible.

      Results:
      Following a launch meeting in April 2015 the trial opened in July (all centres opened October 2015). To help train research staff with introducing the trial to patients, mock patient consultations were recorded. Recruitment was initially slow. Specific research nurse meetings have taken place (December 2015 and June 2016) to understand the barriers to recruitment, centre-specific issues and provide additional education to improve nurses’ confidence in recruiting patients. Regular updates are provided with monthly emails and In February 2016, the Chief Investigator and Trial Manager visited each site to promote the trial and help with any local barriers to recruitment. In response to feedback, changes to the protocol to aid patient recruitment, additional promotional and patient information provided and a video for patients were produced. The study has also been presented at various oncology/thoracic meetings. As a result recruitment has increased with 15 patients successfully randomised into the trial.

      Conclusion:
      Whether SABR is an alternative to surgery is a key question in stage I NSCLC. However, SABRtooth is a challenging study but with a novel trial design and continual adaptive feedback we hope to be able to meet recruitment targets and demonstrate that a definitive phase III RCT is feasible.

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      P1.05-030 - Lung SABR for Early Stage Lung Cancer: Outcomes and Toxicity of 803 Patients Treated at the Leeds Cancer Centre (ID 5874)

      14:30 - 15:45  |  Author(s): P.F. Murray, K. Clarke, K.N. Franks, P. Dickinson, J. Lilley, M.P. Snee, P. Jain

      • Abstract
      • Slides

      Background:
      SABR is an established treatment for early peripheral stage non-small cell lung cancer (NSCLC) in medically inoperable patients We present the outcomes 803 patients, a large prospective series of patients, with a minimum 12 months follow-up after undergoing SABR treatment in Leeds, UK, between May 2009 and May 2015.

      Methods:
      Patients with a pathological or clinical diagnosis of peripheral stage I lung cancer, and deemed medically inoperable, were treated with SABR at the Leeds Cancer Centre, using a dose fractionation of 54Gy/3#, 55Gy/5#, or 60Gy/8# depending on proximity of organs at risk. Patient follow-up was assessed using an electronic patient record and radiology reports. Survival analysis was performed using Kaplein-Meier estimation and log rank test was used to compare survival distibutions including performance status, histology, tumour T stage, tumour location, post-SABR fibrosis, and toxicity.

      Results:
      803 patients were treated with SABR and had at least 12 months follow-up. Mean age at treatment was 73.9 years (39 to 94 years). Median follow-up was 23.3 Months, from time of last treatment fraction to last medical contact or death. Median overall survival estimate was 33.3 Months (95% C.I. 29.54-27.1 Months) 1 year OS – 80.1% (SE 1.4%), 3 year OS – 46.4% (SE 2%), 5 year OS – 29.5% (SE 2.6%) Local control (LC) 1 year LC – 99.2% (SE 0.3%), 2 year LC – 97.2% (SE 0.7%), 3 year LC – 95.1% (SE 0.9%) Both performance status and tumour size were associated with a worse overall survival, Log rank p<0.001 (PS), p=0.035 (T stage). Toxicity Only 4 patients had documented grade 3 toxicity. 3 pneumonitis requiring admission, and 1 patient developed a bronchopulmonary fistula 2 years post-treatment. 44 Patients had a rib fracture recorded, of these 16 patients were symptomatic, and were treated with analgesia or neuropathic adjuncts. 156 patients had documented radiological pneumonitis (gd 1), with 331 developing fibrotic change in the treatment area. Of interest the presence of radiological pneumonitis and fibrotic changes was associated with an improved overall survival, Log rank P=0.009 (Rad pneum), P<0.001 (Fibrosis).

      Conclusion:
      SABR for early stage lung cancer is a safe and effective treatment even in medically inoperable patients, with excellent local control. In our cohort, we found radiological pneumonitis and fibrosis was associated with an improved overall survival, which may be indicative of the patient response to SABR, and will need further evaluation. Performance status and tumour size were associated with a poorer overall survival.

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      P1.05-031 - Primary Results of Dose Escalated Stereotactic Body Radiotherapy for Stage IA Non-Small Cell Lung Cancer (ID 4606)

      14:30 - 15:45  |  Author(s): T. Komiyama, K. Kuriyama, K. Marino, S. Aoki, M. Araya, H. Onishi

      • Abstract
      • Slides

      Background:
      JCOG 0403 showed excellent overall survival in stereotactic body radiotherapy (SBRT) for stage IA non-small cell lung cancer (NSCLC). In Japan, 48Gy/4Fr for isocenter have been the standard dose fractionation of SBRT for stage IA NSCLC. JCOG0702 showed that dose escalation of 55Gy for PTVD~95%~ was feasible in SBRT for peripheral small (PTV volume 100cc or less) NSCLC. Intensification of local treatment with dose escalation is considered to be one of the measures for improvement of overall survival. In 2011, we adopted dose escalated regimen (50Gy/4Fr for PTVD~95%~) for SBRT for stage IA NSCLC, expected improvement of local control and overall survival. The purpose of this study was to review and report the primary results of dose escalated SBRT for stage IA NSCLC.

      Methods:
      From August 2011 to April 2015, 31 patients with stage IA NSCLC were treated with dose escalated SBRT at the University of Yamanashi. The patients' ages ranged from 61 to 86 (median 79) years. Twenty two patients were male, 9 were female. Performance status was 0 in 26, 1 in 5 patients. Tumor histology was squamous cell carcinoma in 6 and adenocarcinoma in 23, other NSCLC in 2 patients. Clinical stage was T1a in 19, T2b in 12 patient. A multiple static ports radiation planned by a radiation treatment planning system (Pinnacle[3] Version 9.2-9.8) was performed with linac using 6MV x-ray beams. The Breath hold technique and CT image guided set-up were used in all cases. A total dose of 50Gy was delivered in 4 fractions over 4-5days. Radiation doses were prescribed to the 95% of planning target volume (PTVD~95%~). A superposition algorithm with heterogeneity correction was used for dose calculations.

      Results:
      The follow-up period for all patients was 3.3-43.1 (median 23.7) months. The overall survival rate at one year and two years were 87.1%, 79.3%, respectively. The local control rate at one year and two years were both 96.4%. Local recurrence, regional lymph node metastases, and distant metastases were observed in 1, 4 and 3 patients, respectively. Regarding to the toxicities, grade 3 radiation pneumonitis were observed in 3 patients. Grade 2 rib fracture were observed in 3 patients. There were no Grade 4 or greater adverse events in the follow-up period.

      Conclusion:
      The toxicity was considered to be acceptable. The local control effect was considered to be sufficient. Longer follow- up durations are needed to validate the clinical benefits of dose escalated SBRT for stage IA NSCLC.

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      P1.05-032 - Quality of Life after Stereotactic Body Radiotherapy and Surgery in Patients with Early Stage Non-Small Cell Lung Cancer (ID 4947)

      14:30 - 15:45  |  Author(s): E.A. Kastelijn, S.Y. El Sharouni, F.N. Hofman, P. Zanen, F.M.N.H. Schramel

      • Abstract
      • Slides

      Background:
      Several studies have shown that the clinical outcomes after stereotactic body radiotherapy (SBRT) are not inferior compared to surgery in patients with early stage non-small cell lung cancer (NSCLC). Quality of life (QoL) after treatment is an important parameter for patients which receives raising interest. We compared the QoL during the first year after treatment in patients with early stage NSCLC.

      Methods:
      Patients diagnosed with early stage NSCLC and treated with SBRT or surgery in the Sint Antonius Hospital between 2013 and 2015 were included. QoL assessments were performed before treatment, and at three, six and 12 months after treatment. QoL was evaluated by using the 30-item European Organization for Research and Treatment of Cancer Quality of life Core questionnaire and its corresponding 13-item lung cancer supplement. A linear mixed model was used to analyse the data and a change of more than five points was determined as minimal clinically important difference .

      Results:
      Ninety-three patients were included (SBRT n = 39, surgery n = 54). Patients who underwent SBRT were significantly older, had a higher ECOG performance status and a lower pulmonary function. The compliance for SBRT and surgery at baseline were 97% and 98% (p = 0.8), at three months 74% and 71% (p = 0.8), at six months 62% vs 78% (p = 0.1), and at 12 months 45% and 73% (p = 0.04). The ECOG performance status was not significantly different between the patients who were compliant and those who were not compliant. During the 12 months after treatment different significant changes were observed: QoL remained stable in SBRT patients and increased in surgical patients (p = 0.012) Role functioning increased in SBRT patients and decreased in surgical patients (p = 0.005) Cognitive functioning increased in SBRT patients and remained stable in surgical patients (p = 0.045) Social functioning remained stable in SBRT patients and decreased in surgical patients (p = 0.001) Pain increased in SBRT patients and decreased in surgical patients (p = 0.001) SBRT patients had a decrease in effect of pain medication and surgical patients had an increase in effect of pain medication (p = 0.0001).

      Conclusion:
      We showed that in patients with early stage NSCLC treated with SBRT or surgery the QoL scores showed different changes after treatment. In the light of the comparable clinical outcomes after both treatments these QoL aspects should be discussed with the patient before making a treatment-decision.

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      P1.05-033 - Comparison of Single- and Five-Fraction Schedules of Stereotactic Body Radiation Therapy for Central Lung Tumors (ID 4394)

      14:30 - 15:45  |  Author(s): S.J. Ma, Y. Syed, C. Rivers, J.A. Gomez Suescun, A.K. Singh

      • Abstract
      • Slides

      Background:
      Stereotactic Body Radiation Therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically inoperable or decline surgery. The safety of 20 Gray (Gy) x 3 fractions of SBRT within 2 cm of the proximal bronchial tree is unclear. Here we compare the clinical outcome of patients with centrally located lung tumors who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years.

      Methods:
      Between January 2009 and October 2014, 11 out of 42 patients received 26-30 Gy in 1 fraction, while the remaining 31 patients received 52.5-60 Gy (median 55 Gy) in 5 fractions. Data were retrospectively collected using an institutional review board-approved database. Kaplan-Meier method, competing risks method, and Cox regression model were used. Toxicities were graded using Common Terminology Criteria for Adverse Events version 4.0. R version 3.3.1 was used for statistical analysis.

      Results:
      After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p=0.64), 1-year overall survival rates for SF- and FF-SBRT groups were 82% and 87%, respectively. There was no statistically significant difference in overall survival (p=0.061), progression-free survival (p=0.47), local failure (p=0.43), nodal failure (p=0.42), and distant failure (p=0.45) at 18 months. No primary tumor failure was seen in both groups at 18 months. Distant failure rates at 18 months were 9.1% for SF-SBRT group and 54.5% for FF-SBRT group. Among the patients with distant failure (n=4 in SF-SBRT and n=6 in FF-SBRT), median time to distant failure was 29.5 months and 8.9 months for SF- and FF-SBRT groups, respectively (p=0.0095). 3 out of 11 patients in SF-SBRT group and 2 out of 32 patients in FF-SBRT group experienced grade 3-4 toxicities. No grade 4-5 toxicities were observed in the FF-SBRT group. SF-SBRT group showed higher cumulative incidence of grade 3+ toxicity at 18 months (p=0.018). However, univariate analysis showed SF-SBRT alone was not a significant factor that increased risk for grade 3+ toxicities (HR=5.50, p=0.063). 4 out of 5 toxicities occurred at least 12 months after SBRT.

      Conclusion:
      SF- and FF-SBRT showed no significant difference in overall survival and local control. No grade 4-5 toxicities were observed in our FF-SBRT group. The onset of distant failure was significantly delayed in the SF-SBRT compared to the FF-SBRT group. The majority of toxicities occurred late. Having SF-SBRT itself was not significantly associated with severe toxicity.

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      P1.05-034 - Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios as Prognostic Biomarkers in Early NSCLC Patients Treated with SABR (ID 6102)

      14:30 - 15:45  |  Author(s): S. McKay, K. Moore, J. Macphee, J. Hicks, G. Lumsden, V. Maclaren, P. McLoone, S. Harrow

      • Abstract

      Background:
      Inflammation may play an important role in cancer progression. High Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) have been reported to be poor prognostic indicators in several malignancies. In this study we quantify the prognostic impact of these biomarkers for overall survival (OS) among early stage NSCLC patients treated with Stereotactic Ablative Body Radiotherapy (SABR).

      Methods:
      102 consecutive patients who received SABR between October 2011 and May 2014 at the Beatson West of Scotland Cancer Centre (BWoSCC) were identified from a prospectively maintained electronic database. NLR and PLR were derived from blood results obtained within 60 days prior to SABR. Receiver Operator Characteristic (ROC) curves were generated to calculate the optimal thresholds for NLR and PLR.

      Results:
      The median age of patients was 72 (range 47-91) years. 60 (59%) were female. Maximum tumour diameter ranged from 10-42mm (median 18mm). Median follow up was 37.1 months. Overall survival at 2 and 4 years was 75.5% (95%CI 65.9-82.7%) and 51.4% (38.8-62.6%) respectively. There was strong association between NLR and PLR levels (r=0.803, p<0.001). ROC Curves indicated a threshold value for NLR of 3.155 (AUC 0.74) and PLR of 155.15 (AUC 0.70) respectively. Median OS for ‘low’ NLR and PLR was not yet reached compared with 33.9 months for ‘high’ NLR (p<0.0001) and 35.4 months for ‘high’ PLR (p=0.002). Multi-variable analysis indicated a stronger independent effect of NLR (p<0.0001), whilst taking account of gender, age, tumour size, histological confirmation and performance status. No association was found between elevated NLR or PLR and loco-regional or distant recurrence.

      Conclusion:
      Neutrophil-to-Lymphocyte Ratio appears to be a prognostic biomarker for patients with early stage NSCLC receiving SABR. Platelet-to-Lymphocyte ratio acts as a linear co-variant. We found no association between elevated NLR or PLR and loco-regional or distant recurrence.

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      P1.05-035 - SABR for Medically Inoperable Early Stage NSCLC at the Beatson West of Scotland Cancer Centre: Outcomes and Toxicity (ID 4798)

      14:30 - 15:45  |  Author(s): S. McKay, K. Moore, J. Macphee, J. Hicks, G. Lumsden, V. Maclaren, A. Aitken, D. Stobo, G. Cowell, P. McLoone, S. Harrow

      • Abstract

      Background:
      SABR is now an established therapeutic option for patients with medically inoperable early stage NSCLC. It is well tolerated and associated with low rates of Grade 3+ toxicity. Here we present the outcomes and toxicity data for the SABR service based at the Beatson West of Scotland Cancer Centre (BWoSCC).

      Methods:
      All 102 consecutive patients (median age 72 (range 47-91) years, 60 (59%) female) who received SABR between October 2011 and May 2014 at the BWoSCC were identified from a prospectively maintained electronic database. Toxicity data was collected at pre-determined intervals in a dedicated follow-up clinic. Radiological evidence of pneumonitis was scored on follow-up CT imaging at 3 months post-SABR. Outcomes were collated from electronic records.

      Results:
      Median and minimum follow-up were 37.1 and 24.1 months respectively. Histological confirmation of NSCLC was available for 33 (32.4%) patients. Local and regional control rates at 2 years were 95.1% and 94.1% respectively. 8.8% of patients developed metastases within 2 years with a median time to detection of metastases of 6.9 months. Overall survival (OS) at 1, 2, 3 and 4 years post-SABR was 88.2% (95%CI 80.2-93.1%), 75.5% (65.9-82.7%), 59.8% (48.2-69.7%) and 51.4% (38.8-62.7%) respectively. No difference in OS was apparent between histologically confirmed and unconfirmed subgroups (p=1.0). On multi-variable analysis, tumour size >= 20mm was negatively associated with OS (p=0.003) whilst gender, age, performance status, deprivation index and histological confirmation were not associated. Radiological scoring of post-SABR pneumonitis was available for 69 patients. A total of 33 of these patients (48%) had radiological evidence of pneumonitis. No association between V5 or V20 and radiological pneumonitis was identified. One death occurred that was potentially related to radiation pneumonitis. Otherwise, only 1 patient experienced grade 4 toxicity (fatigue) and 5 patients (4.9%) reported grade 3 toxicity (4x dyspnoea, 1x fatigue) within 12 months of SABR. There were 4 instances of rib fracture with no association with maximum chest wall dose.

      Conclusion:
      Within the Beatson West of Scotland Cancer Centre the use of SABR for early stage NSCLC is associated with high rates of loco-regional control. Our overall survival and toxicity data compare favourably with published series.

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      P1.05-036 - A Propensity-Matched Study of Multi-Port versus Single-Port Video-Assisted Thoracoscopic Surgery for Early Lung Cancer (ID 4595)

      14:30 - 15:45  |  Author(s): K. Hirai, S. Takeuchi, J. Usuda

      • Abstract
      • Slides

      Background:
      Several thoracic surgeons have already reported the beneficial effects of single-port (SP) video-assisted thoracoscopic surgery (VATS) for the patients with lung cancer. We also analyzed surgical outcomes between SP VATS and multi-port (MP) VATS, which was defined as surgery through 3-4 ports alone, and showed the inhibitory effect of postoperative wound pain in the SP VATS (Eur J Cardiothorac Surg 2015 ). In this study, we aimed to compare the effectiveness of SP and MP video-assisted thoracoscopic surgery for stage I lung cancer.

      Methods:
      A total of 212 patients with non-small cell lung cancer underwent lobectomy via SP and MP procedure between April 2008 and June 2015 in our institute. We examined the a propensity-matched analysis, perioperative variables and short-term outcomes of both operations.

      Results:
      Propensity matching produced 80 pairs in each group. The clinical outcomes of SP /MP group were as follows. The mean Fev1.0 and maximum size of tumor was 1.88±0.32/1.65±0.41 liter and 2.8±0.3/2.7±0.3 cm, respectively. The median operation time, intraoperative blood loss was 165±35/172±26 min. and 85±25/75±26 ml. The median drainage duration and postoperative hospital stay were 1.8±0.7/1.9±0.8 and 7.5±1.9/7.2 ±1.8 days and the mean number of dissected lymph nodes was 19.8±3.8/17.5± 3.1. The number of days that was used with analgesic agents within a month after surgery was 8.1±1.2/12.5±2.5 (P<0.05). Conversion rate to open thoracotomy was 3.9/3.6 %. The overall 3-year disease free survival rate was 92/88%. As for mortality and morbidity, there was no significant difference in both groups.

      Conclusion:
      SP VATS lobectomy, showing alomost as effective as the MP VATS should be considered as a new treatment option for stage I lung cancer.

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      P1.05-037 - Histopathologic Results of Surgically Resected Pure Ground-Glass Opacity Lung Nodules (ID 6269)

      14:30 - 15:45  |  Author(s): G.D. Lee, C.H. Park, Y.W. Do, S. Lee

      • Abstract

      Background:
      Little is known about the histopathology of persistent pure ground-glass opacity lung nodules (GGNs).

      Methods:
      We reviewed preoperative chest computed tomography (CT) in patients who underwent surgery for GGNs between Mar. 2015 and May 2016. A total of 58 surgically resected pure GGNs persistent more than 3 months and their diameter at CT scan less than 15 mm in 41 patients were included. Then pathologic reports of 58 GGNs were retrospectively reviewed.

      Results:
      Median age of the patients was 58 years (range, 33 – 75) and 34 patients (83.3%) were female. Median preoperative follow-up duration of GGNs was 11 months (range, 3–114). In spite of all patients were asymptomatic, the reasons of check-up the chest CT included to follow-up for other malignant disease in 29 patients (70.1%), routine health check-up in 10 (25.0%), and to follow-up of other benign disease in 2 (4.9%). Among a total 45 operations, preoperative CT-guided localization was performed in 31 operations (68.9%). Extents of resection included wedge resection in 29 patients (64.4%), segmentectomy in 7 (15.6%), and lobectomy in 9 (20.0%). Lymph node sampling or dissection was performed in 27 operations (60.0%). Among 58 resected GGNs, median diameter of GGNs was 8mm (range, 3-15mm), median number of resected GGN per operation was 2 (range, 1-5). The distribution of pathologic diagnosis included benign disease in 3 GGNs (5.2%), atypical adenomatous hyperplasia (AAH) in 4 (6.9%), adenocarcinoma in situ (AIS) in 17 (29.3%), minimally invasive adenocarcinoma (MIA) in 19 (32.8%), and invasive adenocarcinoma (IA) in 15 (25.9%). The diameter of GGNs classified into 3 categories (0 – 5mm, 6 – 10mm, 11 – 15mm) were associated with pathologic invasiveness (Cochran-Amitage test, p = 0.005). However, follow-up duration of GGNs classified into 3 categories (3 - 12 months, 13 - 24 months, more than 25 months) was not associated with diameter of GGNs (p = 0.453) or pathologic invasiveness (p = 0.893). Among 18 GGNs tested, epidermal growth factor receptor (EGFR) mutations were detected in 5 GGNs (27.7%).

      Conclusion:
      The prevalence of lung adenocarcinoma (AIS, MIA, IA) was 87.9% in surgically resected pure GGNs persistent more than 3 months and their diameter at CT scan less than 15 mm. A diameter of GGNs diameter was associated with pathologic invasiveness. Further studies are needed for persistent pure GGNs not affected by partial-volume effect of CT in non-selected patients.

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      P1.05-038 - Patterns of Recurrence in Curatively Resected Stage I Lung Cancer (ID 6300)

      14:30 - 15:45  |  Author(s): K. Lee, D.K. Kim, S. Park, Y. Kim, H.R. Kim, S.H. Choi, H.P. Lee, B.K. Chong, J.S. Bok, S.K. Hwang

      • Abstract
      • Slides

      Background:
      The patterns of recurrence after curative resection for pathologically stage I non-small cell lung cancer(NSCLC) were investigated according to the cell type.

      Methods:
      The medical records of stage I NSCLC patients who undergone curative resection at Asan Medical Center between 2000 and 2009 were reviewed.

      Results:
      Total 940 patients with pathologically proven stage I NSCLC were included. Patients with lepidic-type adenocarcinoma(LTA) were 74, other adenocarcinoma(ADC) 580, and squamous cell carcinoma(SCC) 246. Median length of follow-up was 62 months(3~189), median survival was 146 months, and median disease-free survival(DFS) was 109 months. During follow-up, recurrence occurred in 221 patients(23.5%). Number of recurrence is grouped by every 6 months. Incidence of recurrence was peaked within 2 years after resection, then gradually decreased thereafter. Recurrence LTA(AIS/MIA) group was significantly rare(13.5%) throughout the all follow-up period(median DFI of 60months), and its distribution shows relatively even distribution. Comparing ADC and SCC, ADC seemed to show better 5-year OS in univariate analysis(p=0.003), but not in multivariate analysis. Furthermore, there were no significant difference in 5-year DFS(p=0.331). ADC shows higher proportion of distant metastasis, even though ADC group has lower T-stage. SCC shows higher incidence of local recurrence. Figure 1



      Conclusion:
      Recurrence of ADC occured within 2 years after resection, and shows higher proportion of distant metastasis(74.0% Vs. 57.2) even though ADC group has lower T-stage. Most of recurrence of both ADC and SCC groups were peaked within 2 years after resection. LTA group shows significantly delayed pattern of recurrence.

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      P1.05-039 - Recurrence and Survival Outcome after Segmentectomy for Non-Small Cell Lung Cancer: A Long-Term Follow-Up Study at a Single Institute (ID 5011)

      14:30 - 15:45  |  Author(s): T. Koga, K. Fujino, K. Yoshimoto, K. Ikeda, Y. Sato, T. Ito, T. Mori, M. Suzuki

      • Abstract

      Background:
      This study aimed to investigate the factors associated with long-term outcomes of segmentectomy for non-small cell lung cancer (NSCLC) carried out at a single institute.

      Methods:
      179 patients with stage I NSCLC who underwent a segmentectomy between 2005 and 2009 were investigated. Histological classification was reassessed according to the criteria of the 2015 WHO.

      Results:
      179 patients with stage I NSCLC (159 adenocarcinomas (ADCs), 14 squamous cell carcinomas (SQCs), 4 adenosquamous carcinomas, and 2 typical carinoids) who underwent segmentectomy between 2005 and 2009 were investigated.The mean follow-up was 73 months. The 5-year overall survival (5-OS) and 5-years disease-free survival (DFS) were 91.8% and 90.2%, respectively. Seven cases of distant recurrence and 8 local-regional recurrence occurred. Multivariate analysis revealed that lymphovascular invasion (LVI) was the independent predictor of 5-OS (P=0.005), and part-solid GGO (GGO ratio < 50%) and LVI were that for 5-DFS (P=0.043, P<0.001). Among invasive ADC patients, micropapillary pattern (MIP) ≧ 5% was identified as an independent predictor of recurrence (P=0.005) and survival (P=0.007). There were five local recurrences in patients with MIP more than 5 years after segmentectomy. Figure 1



      Conclusion:
      LVI was an independent predictor of the recurrence and overall survival. In patients with invasive ADC, MIP≧5% was a multivariable predictor of recurrence and overall survival. In the patients who underwent a segmentectomy, 5 years without recurrence is not sufficient to conclude that patients with NSCLC is cured.

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      P1.05-040 - Prognostic Factor of Node Involvement Pattern in Completely Resected pN1 Squamous Cell Carcinoma Patients (ID 3971)

      14:30 - 15:45  |  Author(s): K. Tane, K. Miura, H. Okuma, Y. Kitamura, W. Nishio, M. Yoshimura

      • Abstract
      • Slides

      Background:
      In patients with non-small cell lung cancer, the degree of regional lymph node involvement is an important prognostic factor. The prognostic significance of lymph node involvement pattern is unclear in the seventh edition of TNM classification. Squamous cell carcinoma (SCC) often arises in the central way and directly invades intrapulmonary and hilar lymph nodes. In this study, we reviewed our population of operated SCC patients classified as pathologically N1 (pN1) to evaluate the association between N1 lymph node involvement patterns and the prognosis.

      Methods:
      From our institutional database of 3,264 consecutive patients underwent surgical resection for NSCLC at our hospital between January 1987 and December 2010, we examined 152 patients with completely resected pN1 squamous cell carcinoma. We performed reassessment of the data according to the seventh edition of TNM classification of lung cancer. We divided the patients into two groups based on lymph node involvement pattern; direct and separate pattern. The direct pattern was defined as lymph node metastasis by the primary tumor directly with continuity, separate pattern as metastasis without continuity. Survival curves were generated by the Kaplan-Meier method and multivariate analysis was based on the Cox proportional hazards model.

      Results:
      In the lymph nodes metastasis pattern, 75 (49%) patients were the direct group, 77 (51%) patients were the separate group. The percentage of sleeve lobectomy was significantly higher in the direct group and lobectomy without bronchoplastic procedure was higher in the separate group. The median follow-up period was 50 months. The 5-year survivals of the direct and separate group were 54% and 41% (p = 0.01). The 5-year survival of patients with the direct group was as good as pN0 patients (p = 0.78). No survival difference between the separate group and pN2 patients was noted (p = 0.06). Overall recurrence rate of the direct group (44% [33/75]) was lower than the separate group (50% [39/77]), but there was no significant difference among them (p = 0.09). No significant difference was noted in recurrence pattern (distant or locoregional) when comparing the direct group or separate group (p = 0.27). By multivariate analyses of survival, lymph node involvement pattern (p = 0.02) and lymphatic infiltration (p = 0.02) was independent prognostic factor.

      Conclusion:
      Lymph node involvement pattern of patients with pN1 squamous cell carcinoma is significant prognostic factor. Survival of the direct pattern is higher than the separate pattern.

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      P1.05-041 - Dynamics of Brain Metastasis for Curatively Resected Stage I or II Non-Small Cell Lung Cancer Patients (ID 5933)

      14:30 - 15:45  |  Author(s): S. Shin, B.J. Park, J.H. Cho, H.K. Kim, Y.S. Choi, J.I. Zo, Y.M. Shim, J. Kim

      • Abstract

      Background:
      Development of brain metastasis results in a significant impairment in overall survival. The aim of this study to investigate the timing and manifestation of brain recurrence event during follow-up in patients undergoing surgery for stage I or II non–small-cell lung cancer (NSCLC).

      Methods:
      Between 2008 and 2012, medical records for patient who underwent curative surgery for stage I or II NSCLC at our institution were reviewed retrospectively. Event dynamics including brain metastasis, distant metastasis and non-brain distant metastasis, based on the hazard rate, were evaluated.

      Results:
      A total of 2389 eligible patients were identified. At a median follow-up of 50.6 months (IQR, 37.8–60.3 months), 573 patients developed recurrence. Among those, 457 patients had distant metastasis including 70 patients had brain metastasis as the first relapse site. The hazard rate curve for brain metastasis is similar from those of all distant metastasis and non-brain distant metastasis. The distinct surge was noted in 8.3 months in the brain metastasis. Subgroup analysis according to pathologic stage revealed that patients with stage II have distinct surge in 10 months, while the surge of stage I patients is more gradual and low. Hazard rate for brain metastasis is similar for each stage since 34months.

      Conclusion:
      Brain recurrence dynamics of resected stage I or II early-stage NSCLC displays a similar pattern compared to other distant metastasis. The overall risk reached high less than 1 year postoperative period regardless of stage. Our findings would be helpful to make a strategy to surveillance for brain metastasis after surgical resection for early stage NSCLC.

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      P1.05-042 - Treatment Strategy of Limited Surgery for Early Lung Cancer (ID 4497)

      14:30 - 15:45  |  Author(s): K. Kojima

      • Abstract
      • Slides

      Background:
      The standard surgical procedure for operable lung cancer is lobectomy with lymph node dissection. However early lung cancer cases have been increasing in Japan and they have been able to be candidates for limited operation. We have predicted early lung cancer depending on image findings and performed a limited operation positively.

      Methods:
      The advisability of the limited operation is evaluated with computed tomography (=CT) and positron emission tomography (=PET) for the cases in which we have diagnosed a lung nodule as c-Stage IA by staging of lung cancer. We have judged surgical indication for limited operation when the tumor diameter in mediastinal window setting of high resolution CT is 5mm or less and SUVmax level in tumor portion is 1.5 or less even if it exceeds 5mm. We decided the orientation as follows: Wide wedge resection is performed for pure GGO (=ground glass opacity) based on expectation to be Adenocarcinoma in situ (=AIS). Segmentectomy with lymph node dissection is performed for mixed GGO to deal when it is difficult to distinguish whether that the lesion is AIS, Minimally Invasive Adenocarcinoma (=MIA) or Invasive Carcinoma. We examined whether each surgery method was appropriate compared with the postoperative pathological result.

      Results:
      Surgical treatment for lung cancer was performed to 453 cases in our hospital between Apr.2010 and Jun.2016. 115 cases were diagnosed as early cancer suspected in preoperation by the above criteria. Wide wedge resection was performed to 27 cases (31 lesions). 30 lesions were AIS and 1 lesion was MIA pathologically. We underwent left S9 segmentectomy with lymph node dissection in addition for 1 case of mucinous adenocarcinoma. Segmentectomy with lymph node dissection was performed to 58 cases (61 lesions). 26 lesions were AIS, 29 lesions were MIA, 5 lesions were invasive adenocarcinoma and 1 lesion was squamous cell carcinoma pathologically. In all cases of invasive adenocarcinoma and squamous cell carcinoma, both lymph node metastasis and lymphovascular invasion was negative, so we did not perform completion lobectomy in addition. We performed lobectomy to 23 cases in spite of our expectation as early cancer due to a lesion of the middle lobe, a lesion near pulmonary hilum or the request of the patients and pathological results were 7 AIS, 7 MIA and 9 invasive adenocarcinoma with no lymphovascular invasion and no lymph node metastasis.

      Conclusion:
      We can operate for the appropriate extent of resection for early lung cancer by making full use of image findings.

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      P1.05-043 - Survival Following Surgical Resection of Lung Adenocarcinoma Stratified According to Morphological Sub-Type (ID 4494)

      14:30 - 15:45  |  Author(s): H. Balata, T. Edwards, C. Tennyson, P. Foden, A. Chaturvedi, P. Crosbie, R. Booton, M. Evison

      • Abstract
      • Slides

      Background:
      Lung adenocarcinoma is the commonest histological sub-type of Non-small cell lung cancer (NSCLC) and a leading cause of death worldwide. Identifying factors that may influence survival or the risk of recurrence following resection of lung adenocarcinoma may inform adjuvant strategies and the intensity of surveillance programs. The aim of this study was to assess the effect of morphological sub-type on survival following surgical resection.

      Methods:
      Patients who underwent surgical resection for non-small cell lung cancer between 2011 and 2014 at a tertiary thoracic surgical and lung cancer centre were identified from pathological records (n=1387). Patients with adenocarcinoma (n=705) were selected and the predominant morphological subtyping was recorded. Survival data was obtained from national death registries.

      Results:
      Of the 705 adenocarcinomas, Acinar (n=325), Lepidic (n=133) and Solid (n=131) were the most frequent histological subtypes identified. Numbers for other subtypes were small and therefor 3 year survival was not always possible to calculate.

      Survival by histological subtypes
      Histology No. of Deaths during follow-up 1 year survival 2 year survival 3 year survival
      Acinar (N=325) 93 90.5% 79.2% 68.3%
      Glandular (N=17) 5 94.1% - -
      Lepidic (N=133) 32 92.5% 84.4% 76.6%
      Micropapillary (N=3) 1 - - -
      Mixed (N=26) 9 84.6% 71.3% -
      Papillary (N=38) 11 78.9% 76.3% -
      Solid (N=131) 50 81.7% 67.1% 59.7%
      Unknown (N=31) 10 93.5% 71.5% -


      Conclusion:
      A difference in survival can be seen between the three commonest adenocarcinoma subtypes (Acinar, Lepidic and Solid) at 1, 2 and 3 years following surgical resection. Interpreting results on other sub-types is limited by small numbers. Lepidic and Solid have the best and worst survival rates respectively. Limitations include a lack of adjustment for pathological stage or co-morbidities and a lack of cancer-specific mortality data. Future studies may evaluate if the morphology of lung adenocarcinomas could have a role in defining adjuvant and surveillance strategies.

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      P1.05-044 - The Impact of IASLC 8th Edition Updates for T-Classification for Lung Cancer in a US Population-Based Surgical Resection Cohort (ID 6241)

      14:30 - 15:45  |  Author(s): M.P. Smeltzer, N.R. Faris, C. Fehnel, C. Houston-Harris, M.A. Ray, Y. Lee, M.B. Meadows, S. Signore, C. Mutrie, E.T. Robbins, R.U. Osarogiagbon

      • Abstract
      • Slides

      Background:
      Accurate staging of non-small cell lung cancer (NSCLC) is vital for prognostication and treatment selection. We evaluated the impact of the 8[th] Edition TNM (8E) T-classification in a US regional NSCLC resection database.

      Methods:
      Curative-intent NSCLC resections from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions within 3 US states from 2009-2016 were re-staged based on 8E T-categorization. Survival analyses were conducted using the Kaplan-Meier method and proportional hazards models with adjusted hazard ratios (aHR) controlling for age, histology, grade, pN-category, and comorbidities. M1 patients and those who received neoadjuvant therapy were excluded.

      Results:
      The 2245 patients had a median age of 65, were 48% female, 78% white, 21% black. The 961 pT1 (8E) distribution was 10% pT1a, 52% pT1b, and 39% pT1c. The 793 pT2 (8E) patients were 82% pT2a and 18% pT2b. Of the 318 patients with pT3 (8E), 134 (42%) were pT2b based on the 7[th] Edition TNM (7E); of the 152 with pT4 (8E), 107 (70%) were pT3 based on 7E. There was no survival difference between pT1a and pT1b (p=0.83); pT1c had worse survival than pT1b (p<0.01; Figure 1a). Of the 145 patients previously classified as pT2b by 7E, 134 (92%) were upstaged to pT3. They had similar survival to those classified as pT3 in 7E (p=0.75). Of the 296 patients previously classified as pT3, 107 (36%) were upstaged to pT4. The upstaged patients had worse survival than 7E pT3 patients who were not upstaged, although not statistically significant (aHR:1.32, Figure 1b). Adjusted models confirm an increasing trend in the hazard of death with increasing stage, with the exception of pT1b. (aHR: pT1a=1.00, pT1b=0.89, pT1c=1.15, pT2a=1.38, pT2b=1.54, pT3=1.86, pT4=2.44). Figure 1



      Conclusion:
      This analysis independently corroborates the 8E re-classification for late stage patients in the US. However, we found no survival differentiation between tumors less than 2cm.

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      P1.05-045 - Adjuvant Chemotherapy for Patients with Stage IB Non Small Cell Lung Cancer (ID 4565)

      14:30 - 15:45  |  Author(s): J. Wang, Y. Yue

      • Abstract
      • Slides

      Background:
      The prognosis of stage Ib non-small cell lung cancer (NSCLC) remains poor, there’re much controversy over the necessity of adjuvant chemotherapy to them. The aim of this study is to investigate the clinical characters influencing prognosis of the stage Ib non-small cell lung cancer (NSCLC) and to explore the indication of postoperative chemotherapy.

      Methods:
      In total, 569 stage IB patients with NSCLC who underwent surgical resection with or without adjuvant therapy were included in this study. Cox proportional-hazards ratios were used to identify independent prognostic factors for survival. Kaplan-Meier survival curves were calculated to estimate survival rates.

      Results:
      Adjuvant chemotherapy, tumor size and performance status were independent prognostic factors in the univariate and multivariate analyses. Patients with tumor greater than 4 cm and patients with good performance status benefitted from adjuvant chemotherapy. On the contrary, to the patients with tumor less or equal to 4 cm or patients without good performance status, giving adjuvant chemotherapy is not better than giving surgery alone. Figure 1 Figure 2





      Conclusion:
      Adjuvant chemotherapy, tumor size and performance status were closely correlated with survival in the stage Ib NSCLC, patients with tumor greater than 4 cm and patients with good performance status benefitted from adjuvant chemotherapy.

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      P1.05-046 - Randomized Study of Adjuvant Docetaxel vs. Observation for Completely Resected StageⅠB-Ⅲa NSCLC with 11 Years' Median Follow-Up (ID 5722)

      14:30 - 15:45  |  Author(s): W. Zhong, X. Yang, H. Yan, R. Liao, Q. Nie, S. Dong, B. Jiang, Q. Zhou, J. Yang, Y.-. Wu

      • Abstract

      Background:
      Although previous meta-analyses have verified the significance of adjuvant chemotherapy, the role of adjuvant carbopatin plus docetaxel(DC) among patients with completely resected NSCLC with long periods of follow-up remains unclear.

      Methods:
      Eligible patients were randomly assigned to 4 cycles of DC or observation after complete resection. The primary end point was DFS; secondary ones were OS, the toxicity and safety of drugs. An increase of 15% in 1-year survival rate (observation arm 70%) with a sample size of 270 patients was considered significant.

      Results:
      This trial was suspended prematurely in June 2005 due to the negative survival benefits from chemotherapy in stage IB patients in the JBR10 trial. 82 patients were enrolled between 2002 to 2005(43 and 39 in each arm).Two arms were well-balanced on age, gender, histology, smoking history and staging. Median follow-up was 11 years(10.5-13y). DFS was marginally significantly longer in DC arm than observation (10.4 vs. 3.7y; HR=0.58; 95% CI, 0.33-1.03; P=0.06), as was 5-year DFS rates(63% vs. 41%, P=0.057). No statistical significance existed in OS (NR vs. 7.1y; P=0.103) or 5-year survival rates(76% vs. 61%; P=0.148). Multivariable analysis revealed patients receiving adjuvant DC(HR=0.54,95%CI 0.30-0.96,P=0.036) and with stage IB disease(HR=0.34,95%CI, 0.19-0.61,P<0.001) bore lower recurrence risk. In DC arm, 84% of patients received at least one cycle of DC, and 53% of patients finished four. Grades 3 adverse events occurred in 5%(2/43) in chemotherapy group. The time-varying endpoints showed adjuvant DC could delay the recurrence and mortality in the first postoperative 5ys, while two arms tended to be equivalent after 5ys. Figure 1



      Conclusion:
      This is the first randomized trial used DC as adjuvant chemotherapy suggesting a potentially significant role for completely resected early stage NSCLC with safety and compliance. Additionally, at least 10ys’ follow-up for each patient was vital to investigate the long-term time-varying recurrence and mortality pattern.

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      P1.05-047 - Early Mortality in Patients with Non-Small Cell Lung Cancer Undergoing Adjuvant Chemotherapy (ID 5523)

      14:30 - 15:45  |  Author(s): D. Morgensztern, P. Samson, S.N. Waqar, L. Du, S. Devarakonda, A. Masood, C. Robinson, V. Puri, R. Govindan

      • Abstract

      Background:
      Although adjuvant chemotherapy improves survival in patients with completely resected non-small-cell lung cancer (NSCLC) compared to surgery alone, it is also associated with potentially disabling or lethal adverse events. Since there is limited information on the early mortality among patients undergoing adjuvant chemotherapy, we used the National Cancer Data Base (NCDB) to calculate the percentage of deaths within the first 6 months from starting chemotherapy.

      Methods:
      The NCDB was queried for patients aged 18 or older, diagnosed with stage IB to IIIA NSCLC (AJCC 7[th] edition) from 2004 to 2012, who underwent surgery with negative margins followed by multi-agent chemotherapy, starting within 120 days from the surgical resection. Patients who received radiation therapy were excluded. Age groups were divided into <50, 51-60, 61-70, 71-80 and >80 years. Early mortality from months 1 to 6 were calculated and multivariate logistic regression was performed to identify clinical variables independently associated with mortality at six months from the date of initiation of adjuvant chemotherapy.

      Results:
      A total of 19,791 patients met the eligibility criteria. The median age was 65 (range 19-89). The percentage of deaths at 1, 2, 3, 4, 5 and 6 months were 0.6%, 1.3%, 1.9%, 2.6%, 3.3% and 4.2% respectively. The percentages of death at 6 months for each age group from < 50 years to > 80 years were 2.7%, 3.2%, 4.1%, 5.3% and 7.8% respectively. Factors independently associated with increased 6-month mortality included increased age, male gender, higher Charlson-Deyo co-morbidity score (CDCS), type of surgery, length of stay (LoS) > 6 days and 30-day readmission (Table).

      Conclusion:
      There is a high risk for early mortality among patients undergoing adjuvant chemotherapy for NSCLC, particularly in patients older than 70, with high co-morbidity score and a more complicated post-operative period.

      Table. Multivariable analysis
      Variable OR (95% CI) P-value
      Age
      ≤ 50 Reference Reference
      51-60 1.08 (0.74-1.60) 0.68
      61-70 1.33 (0.91-1.95) 0.15
      71-80 1.59 (1.06-2.38) 0.03
      > 80 2.27 (1.29-3.98) 0.004
      Gender
      Male Reference Reference
      Female 0.70 (0.59-0.82) < 0.001
      CDCS
      0 Reference Reference
      1 1.13 (0.95-1.34) 0.15
      2 1.58 (1.26-1.98) < 0.001
      Surgery
      Sub-lobar Reference Reference
      Lobectomy 0.72 (0.53-0.97) 0.03
      Pneumonectomy 0.97 (0.68-1.39) 0.87
      Stage
      IB Reference Reference
      II 1.29 (1.04-1.59) 0.02
      IIIA 2.28 (1.81-2.87) < 0.001
      LoS
      ≤ 6 days Reference Reference
      > 6 days 1.24 (1.06-1.46) 0.008
      30-day readmission
      No Reference Reference
      Yes 1.54 (1.20-1.99) 0.001


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      P1.05-048 - Effect of Adjuvant Chemotherapy on the Patterns and Dynamics of Recurrences in Resected Stage II(N1) Lung Adenocarcinoma (ID 4990)

      14:30 - 15:45  |  Author(s): B.J. Park, Y.S. Choi, J.H. Lee, H.K. Kim, J.H. Cho, J.I. Zo, Y.M. Shim, S. Shin, M. Ahn, J.S. Ahn, K. Park, J. Kim

      • Abstract
      • Slides

      Background:
      Although the complete surgical resection in most cases of the non-small cell lung carcinoma with N1 involvement is feasible, a considerable number of patients develop recurrence and the disease course is highly variable. Timing and pattern of recurrence are essential to explain strong prognostic heterogeneity, however, research focusing on these subjects have rarely been reported. We investigated the patterns of recurrences and event rates over time in patients with completely resected N1-stageII lung adenocarcinoma.

      Methods:
      We retrospectively reviewed the medical records of 333 patients who underwent a complete surgical resection for N1-stage II lung adenocarcinoma. Survival curves were generated using the Kaplan-Meier method, and the event dynamics was estimated using the hazard function.

      Results:
      The median recurrence-free survival was 36.8 months. The life table survival analysis showed that the 1-year, 3-year and 5-year recurrence free survival rates were 85.1%, 50.2% and 36.6%, respectively. Approximately 151(45.2%) patients experienced recurrence, and the patterns of recurrences included loco-regional in 41 patients (27.2%), distant in 68 (45.0%), and both in 42 (27.8%). Most commonly involved organs were the lung (n=77, 47.0%), followed by lymph nodes (n=41, 27.2%), bone (n=31, 20.5%), and brain (n=30, 19.9%). There were 228 patients received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy showed better recurrence free survival (chemotherapy group vs non-chemotherapy group; median survival 42.5 months vs 25.4 months), and post-recurrence survival(chemotherapy group vs non-chemotherapy group; median survival 39.8 months vs 22.6 months) compared to those of patients without adjuvant chemotherapy. The multivariate analysis revealed that adjuvant chemotherapy was significantly correlated with recurrence free survival (p=0.004) and post recurrence survival (p=0.001). Patients underwent adjuvant chemotherapy had less distant (p=0.014) and less lung (p=0.045) recurrence, while there is no difference in loco-regional (p=0.837) and brain (p=0.997) recurrence. The recurrence hazard curve demonstrated similarly shaped and sized initial and second peak at 16 and 24months, followed by a smaller peak at 40months. The temporal distribution of the recurrence risk varied depending on adjuvant chemotherapy. A visual inspection of the hazard curves suggested that the patients without adjuvant chemotherapy exhibited earlier and higher first peaks with higher hazard rate over time.

      Conclusion:
      In the patients who underwent completely resected N1-stageII lung adenocarcinoma, adjuvant chemotherapy not only reduced the recurrence hazard, but also delayed the recurrence, altered pattern of recurrence and improved post-recurrence survival.

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      P1.05-049 - Neoadjuvant Erlotinib Treatment in Patients with Resectable Non-Small Cell Lung Carcinoma (ID 3788)

      14:30 - 15:45  |  Author(s): M.H. Van Gool, H.M. Klomp

      • Abstract

      Background:
      The value of neo-adjuvant therapy in patients with resectable non-small cell lung carcinoma (NSCLC) is limited. Recent advances in targeted therapy have provided novel treatment options for NSCLC with promising results. The Epidermal Growth Factor Receptor (EGFR) is over expressed or may harbour activating mutations in adenocarcinoma in particular. Inhibition of EGFR with tyrosine-kinase inhibitor (TKI) therapy has a favourable outcome in advanced stage patients with activating mutations. The purpose of this study was to prospectively evaluate 18F-FDG-PET metabolic response to neoadjuvant erlotinib, in patients with resectable NSCLC.

      Methods:
      This study was designed as a multicentre open-label phase II trial, performed in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Metabolic response evaluation was performed using FDG-PET/CT scan. Tumour FDG uptake and changes were measured by standardized uptake values (SUV). Metabolic response was classified using EORTC criteria. Metabolic response was compared to the histopathological response and survival.

      Results:
      From December 2006 until November 2010, 60 patients were enrolled in this study. In 43 patients (18 male, 25 female), FDG-PET/CT scans and histopathologic response monitoring were available. 14 patients (33%) showed a metabolic response. Histopathologic examination showed a response in 13 patients (30%). In predicting histopathologic response FDG-uptake showed an area under the curve of 72%. Metabolic responders show an improved overall and progression free survival in comparison to patients without metabolic response.Figure 1



      Conclusion:
      FDG-PET/CT may be used as a predictive tool to identify patients with advantage of neoadjuvant EGFR-TKI treatment in resectable NSCLC.

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      P1.05-050 - External Validation of a Prognostic Model for Squamous-Cell Lung Cancer and Impact of Adjuvant Treatment in >1,300 Patients (ID 5297)

      14:30 - 15:45  |  Author(s): E. Bria, S. Pilotto, I. Sperduti, G. Leuzzi, M. Chiappetta, F. Mucilli, G.B. Ratto, F. Lococo, P.L. Filosso, L. Spaggiari, S. Novello, M. Milella, P. Visca, A. Santo, A. Scarpa, M.V. Infante, G. Tortora, F. Facciolo

      • Abstract
      • Slides

      Background:
      A risk classification model able to powerfully discriminate the prognosis of resected squamous-cell lung cancer (R-SqCLC) patients (pts) was developed (Pilotto JTO 2015). Herein, we validate the model in a larger multicenter series of >1,300 R-SqCLC pts (AIRC project 14282).

      Methods:
      R-SqCLC pts in 6 different institutions (01/2002 - 12/2012) were considered eligible. Each patient was assigned with a prognostic score to identify the individual risk of recurrence, on the basis of the clinico-pathological data according to the develop model (age, T-descriptor according to TNM 7th edition, nodes, and grading). Kaplan-Meier analysis for disease-free/cancer-specific/overall survival (DFS/CSS/OS) was performed according to the published 3-class risk model (Low: score 0-2; Intermediate: score 3-4; High: score 5-6). Harrell’s C-statistics was adopted for model validation. The effect of adjuvant chemotherapy (ACT) was adjusted with the Propensity Score (PS).

      Results:
      Data from 1,375 pts from 6 institutions were gathered (median age: 68 years; male/female: 86.8%/13.2%; T-descriptor 1–2/3–4: 73.3%/26.7%; nodes 0/>0: 53.4%/46.6%; stages I-II/III-IV: 71.7%/28.3%); 384 pts (34.5%) underwent ACT. With a median follow-up of 55 months (95% CI 51-59), pts at Low-Risk had a significantly longer DFS in comparison with Intermediate- (HR 1.67, 95% CI 1.40-2.01) and High-Risk (HR 2.46, 95% CI 1.90-3.19) pts, as well as for CSS (HR 1.79, 95% CI 1.48-2.17; HR 2.33, 95% CI 1.76-3.07) and OS (HR 2.46, 95% CI 1.80-3.36; HR 4.30, 95% CI 2.92-6.33). C-statistics was 68.3 (95% CI 63.5-73.1), 68.0 (95% CI 63.2-72.9), and 66.0 (95% CI 61.6-71.1), for DFS, CSS and OS, respectively. 60-months DFS for Low-, Intermediate- and High-Risk pts was 51.0%, 33.5% and 25.8%, respectively (p<0.0001). 60-months CSS for Low-, Intermediate- and High-Risk pts was 82.7%, 64.7% and 53.3%, respectively (p<0.0001). 60-months OS for Low-, Intermediate- and High-Risk pts was 56.7%, 37.9% and 30.9%, respectively (p<0.0001). A significant benefit in DFS was found in favor of ACT (p=0.005), with no difference in CSS (p=0.57), although a trend in OS (p=0.16). Overall, no significant differences for ACT were found in DFS, CSS and OS when survival was corrected with PS analysis, although CSS and OS curves visually separate with a trend for ACT in Intermediate- and High-Risk pts.

      Conclusion:
      The prognostic performance of the previously developed model was validated in a larger R-SqCLC pts’ series. Considering the overall dismal prognosis of such disease, the efficacy of ACT requires to be clearly established for Intermediate- and High-Risk pts, as well as that should be questioned for Low-Risk pts.

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      P1.05-051 - Safety and Compliance Data of the Phase III Study of Adjuvant Chemotherapy in Completely Resected P-Stage I Non Small Cell Lung Cancer: JCOG0707 (ID 3877)

      14:30 - 15:45  |  Author(s): H. Kunitoh, H. Sakurai, M. Tsuboi, M. Wakabayashi, M. Okada, K. Suzuki, N. Ikeda, M. Takenoyama, Y. Ohde, M. Takahama, K. Yoshiya, I. Matsumoto, M. Yamashita, T. Marutsuka, H. Date, Y. Saito, Y. Yamashita, N. Okumura, S. Watanabe, H. Asamura

      • Abstract
      • Slides

      Background:
      Post-operative UFT (tegafur/uracil) has been shown to prolong survival of Japanese patients (pts) with completely resected, pathological (p-) stage I (T1> 2 cm) non small cell lung cancer (NSCLC). This trial aimed at estimating the efficacy of S-1 (tegafur/gimeracil/oteracil) compared to UFT as adjuvant therapy in this population.

      Methods:
      Eligible pts had undergone complete resection with lymph node dissection for p-stage I (T1-2N0M0, T1> 2 cm, by 5[th] Edition UICC TNM) NSCLC, within 56 days of enrollment. Pts were randomized to receive either oral UFT 250mg/M2/d for 2 years (Arm A), or oral S-1 80mg/M2/d for 2 weeks followed by 1 week of rest, for 1 year (Arm B). The initial primary endpoint was overall survival (OS). Based upon the results of monitoring in Jun. 2013, which showed the combined OS of the 2 arms better than expected (4-year OS of 91.6% vs. presumed 5-year OS of 70-76.5%), the study was judged to be underpowered. The study protocol was amended so that the primary endpoint was relapse-free survival (RFS). With a calculated sample size of 960, this study would detect the superiority of Arm B over Arm A with power 79% and a one-sided type I error of 0.05, assuming the 5-year RFS of 75% in Arm A and the hazard ratio of 0.75.

      Results:
      From Nov. 2008 to Dec. 2013, 963 pts were enrolled: median age 66 (range: 33 to 80), male 58%, adenocarcinoma 80%, p-T1/T2 46%/54%. Only 2 pts received pneumonectomy. All pts had completed protocol therapy. >Grade 3 toxicities (hematologic/nonhematologic) were observed in 15.9 (1.5/14.7) % in Arm A, and in 14.6 (3.6/11.9) % in Arm B, respectively. In Arm A, 59.5% of the pts completed protocol therapy, and 70.7% received UFT for >1 year, which was comparable to prior studies. In Arm B, 54.7% completed protocol therapy, and 69.9% received S-1 for > 6 months. There were 4 cases of on-protocol deaths, probably of cardio-vascular origin: 1 in Arm A and 3 in Arm B. Based on the 2[nd] interim analysis in Sep. 2015, the data and safety monitoring committee recommended the follow-up of pts without unmasking of treatment arms. Estimated combined 2-year OS and RFS were 97.3% and 89.6%, respectively.

      Conclusion:
      Both post-operative adjuvant therapies were feasible, with similar compliances. Main results will be available in 2019.

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      P1.05-052 - An Exploratory Analysis of Postoperative Adjuvant Chemotherapy with Tegafur-Uracil on Survival for Lung Adenocarcinoma (ID 4551)

      14:30 - 15:45  |  Author(s): M. Tsuboi, C. Hamada, H. Kato, M. Ohta

      • Abstract
      • Slides

      Background:
      The Eighth Edition of the TNM Classification (TNM 8[th]) for non-small cell lung cancer (NSCLC) proposes a more detailed classification of primary tumor diameter (T). Tegafur-uracil (UFT) improves survival in patients with stage I adenocarcinoma of the lung based on the results of Japan Lung Cancer Research Group (JLCRG: Kato H, et al. N Engl J Med. 2004). However, it is controversial whether the effect of UFT on survival in each T category be the same when TNM[8th] is adopted.

      Methods:
      This exploratory analysis was performed on the subgroup of 979 eligible patients in JLCRG study. The hazard ratio and the 95% confidence interval (CI) for overall survival in each T category of TNM 8[th] were estimated using stratified Cox proportional hazards models, stratified by sex and age. The overall survival in each T category was estimated by the Kaplan-Meier method.

      Results:
      The UFT group and the observation group were reanalyzed based on the new classifications of T category defined by TNM[8th], T1a (T, ≤1 cm), T1b (T, >1 to ≤2 cm), T1c (T, >2 to ≤3 cm), T2a (T, >3 to ≤4 cm), T2b (T, >4 to ≤5 cm), and T3 (T, >5 to ≤7 cm). The major prognostic factors did not differ significantly between these two groups in each T category. The benefits of UFT on overall survival varied in each T category (Table 1). Figure 1



      Conclusion:
      UFT tended to improve survival in each T category defined by TNM[8th], except for T1b, when compared to surgery alone.

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      P1.05-053 - Impact of Gender Difference on Adjuvant Chemotherapy after Radical Resection in Patients with Non-Small Cell Lung Cancer (ID 4081)

      14:30 - 15:45  |  Author(s): L. Yang, X. Zhai, W. Ziping

      • Abstract
      • Slides

      Background:
      Gender was an important prognostic factor in patients with advanced non-small cell lung cancer (NSCLC). However, there are few studies reporting the impact of gender difference on the efficacy of adjuvant chemotherapy (ACT) in NSCLC patients.

      Methods:
      900 patients (584 men and 316 women) who received post-operative ACT in the Cancer Hospital of the Chinese Academy of Medical Sciences between 2001 and 2013 with complete records in the database of the hospital were analyzed in this study for analysis. The primary end point was disease-free survival (DFS) in terms of gender. Survival analysis was performed using Kaplan–Meier estimates, log-rank tests and Cox’s proportional hazards regression analysis. Propensity score matching (PSM) was used, and survival analysis of the match data were carried out.

      Results:
      There was no significant difference in DFS between the two groups in terms of gender before propensity score was matched (105.857 weeks [95%CI 86.699, 125.015] vs. 95.714 months [95%CI 81.905, 109.523], P=0.575). Furthermore, no significant impact of gender on DFS was observed between the PS-matched groups (102.429 weeks [95%CI 80.078, 124.779] vs. 99.143 weeks [95%CI 66.539, 131.746], P=0.893).

      Conclusion:
      The results suggest that gender was not a prognostic factor on ACT after radical resected NSCLC. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification.

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      P1.05-054 - Adjuvant Chemotherapy Uptake in Patients with NSCLC after Complete Resection: Single Institution/Single Area Experience (ID 3914)

      14:30 - 15:45  |  Author(s): V. Kolek, I. Grygarkova, J. Kultan, P. Jakubec, M. Szkorupa, J. Klein, C. Neoral, J. Skarda, T. Tichy, Z. Kolar

      • Abstract

      Background:
      Adjuvant chemotherapy (AC) is recommended in patients (pts) with stages IB (tumour of ≥4 cm in diameter), IIA, IIB, and IIIA of non-small cell lung cancer (NSCLC) after complete resection. According to metaanalyses it prolongs survival of pts in good PS and age less than 75 years. The selection of patients is influenced by the limited profit of AC, possible toxicity and the lack of predictive biomarkers. There are only few retrospective studies describing routine utilization of AC in specified areas. Presented AC uptake in stages II and III varies from 20 % to 24% in Canada and USA. .

      Methods:
      A retrospective study of AC uptake in pts with NSCLC from a Moravian region with 600.000 inhabitants was conducted, evaluation period was 2006-2013. Treatment strategy of all patients was discussed by surgeons and pneumo-oncologists on the interdisciplinary tumour boards before and after surgery. Uptake and compliance of AC was evaluated according to age, sex, TNM stages, type of surgery and other cofactors. AC was given in regimens using doublets of platinum with vinorelbine (rarely gemcitabine or paclitaxel). Vinorelbine was applied both intravenously (25 mg/m[2]) and orally (60 - 80 mg/m[2]). The choice of cisplatinum (80mg/m[2]) or carboplatinum (AUC 5) was based on patient preference, PS and comorbidities. .

      Results:
      Out of all 1557 pts with lung cancer, NSCLC was present in 1293 pts. 308 pts underwent curative-intent surgery and complete resection was achieved in 295 pts. 226 pts were pts with stages IB, II and IIIA and AC was applied in 183 pts (80.1%), in 34 (18.6 %) pts together with neoadjuvant chemotherapy. AC was not applied in 43 (19.9 %) pts after radical surgery due to worse PS, comorbidities, complications after surgery or patient´s refusal. The mean age of pts with AC was 65 years, 66,7% were men, 48,9 % women, 49,9 % were current smokers, 40,0% ex-smokers and 10,1 % non-smokers. Age, sex and smoking habits were not statistically different between pts with and without AC. Compliance with AC was very good, 82% of pts accomplished planned therapy.

      Conclusion:
      The optimal uptake of AC in routine practice depends on the intensive communication between the patient, surgeons and pneumoocologists. The individual decision is important in a context to the patients´ health status, tumour parameters and the potential risk/ benefit of therapy. Study was supported by grant AZV 16-32318A

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      P1.05-055 - Risk Factors of Postoperative Recurrence in Stage IA and IB Patients (ID 5606)

      14:30 - 15:45  |  Author(s): F. Hoshi, A. Sakurada, T. Hasumi, T. Sado, M. Noda, Y. Matsuda, S. Eba, H. Mitomo, T. Togo, M. Katahira, Y. Okada

      • Abstract

      Background:
      The 5-year survival rates of the patients with pathological stage IA and IB NSCLC have been reported 86-93% and 67-84%, respectively. Among stage I disease, patients with stage IA of tumor diameter over 20 mm as well as stage IB are recommended to take oral UFT as adjuvant chemotherapy for 2 years in Japan. Even after complete resection and such adjuvant therapy, we still observe recurrence at a certain rate. Identifying clinicopathological factors which is associated with recurrence would be beneficial to establish alternative strategy. The purpose of this study is to identify the predictive factors for recurrence in the patients with stage I NSCLC.

      Methods:
      A total of 742 stage I NSCLC patients who underwent complete resection in our hospital from 1996 to 2012 were retrospectively analyzed. Medical records of these patients were reviewed carefully. The median age was 66.4 years with 512 stage IA and 281 stage IB. Histopathologically, there were 590 adenocarcinoma, 150 squamous cell carcinoma, 32 large cell carcinoma, and 21 other histology cases. Surgical procedure was segmentectomy, lobectomy, and pneumonectomy for 46, 588, and 8 patients, respectively. Clinicopathological factors such as smoking history, histology, pathological vascular invasion (v), and lymphatic vessel invasion (ly) were analyzed.

      Results:
      Recurrence occurred in 132 cases. Multivariate analysis showed that T factor, v(+), ly(+), and smoking history have statistical significance with recurrence. n pT1a and T2a cases, there were no statistical significance between recurrence and pathological ly(+) and/or v(+). But only in T1b cases, ly(+) and/or v(+) had statistical significance with recurrence.

      Conclusion:
      We identified that T factor, v, ly, and smoking history were predictive factors for recurrence in stage IA and IB NSCLC patients. Because of good prognosis, pT1b patients whose both v and ly were negative may not take UFT as adjuvant chemotherapy.

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      P1.05-056 - Increased Risk of Postoperative Recurrence in EGFR-Positive Stage IA to IB Invasive Lung Adenocarcinoma (ID 4811)

      14:30 - 15:45  |  Author(s): M. Ito, Y. Miyata, K. Kushitani, T. Yoshiya, Y. Tsutani, K. Konishi, Y. Takeshima, M. Okada

      • Abstract
      • Slides

      Background:
      Somatic mutations of EGFR represent one of the most frequent genetic aberrations in lung adenocarcinoma and response to tyrosine kinase inhibitors (TKIs) has been favourable in EGFR-positive and advanced lung adenocarcinoma patients. The prognostic significance of EGFR mutations as oncogenic driver mutations in early-stage lung adenocarcinoma has yet to be determined. We aimed to evaluate the oncological significance of EGFR mutations in early-stage lung adenocarcinoma

      Methods:
      Four hundred and seventy-three consecutive lung adenocarcinoma patients who underwent surgical resection for pathological N0M0 disease, between January 2007 and December 2013, were retrospectively reviewed. The prognostic significance of EGFR mutation status was evaluated in 407 cases from these patients. Overall survival (OS) and recurrence-free interval (RFI) curves were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using a Cox proportional hazards model.

      Results:
      There was no statistical significance in the 5-year OS (89.3 vs. 95.3%, P = .20, HR = 1.605) or RFI (86.5 vs. 93.5%, P = .06, HR = 1.956) rates between the EGFR-positive (n=183) and EGFR-negative (n=224) groups. Considering the risk of recurrence and positive EGFR mutation status, OS and RFI rates were subsequently calculated among specific histological subtypes. After adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive mucinous adenocarcinoma (IMA) cases were excluded, all analysed cases were ≤5.0 cm in tumour diameter and were classified as pathological Stage IA-IB. Among specific histological subtypes, the 5-year RFI (81.5 vs. 92.4%, P = .04, HR = 2.160) but not OS rate (86.8 vs. 94.3%, P = .31, HR = 1.499) was significantly poorer in EGFR-positive cases compared to EGFR-negative cases. Univariate analysis, excluding AIS, MIA, and IMA, identified a pathological tumour size of >3.0 cm, a highly malignant subtype (micropapillary or solid predominant adenocarcinoma), pleural/lymphatic/vascular invasion, and a positive EGFR mutation status as significant negative predictive factors for RFI. Multivariate analysis confirmed pleural invasion and a positive EGFR mutation status as independent negative predictive factors for RFI.

      Conclusion:
      EGFR mutation status is a predictive factor for postoperative recurrence in early-stage lung adenocarcinoma, with the exception of AIS, MIA, and IMA. The risk of recurrence should be considered with EGFR mutation status and predominant histological subtype in resected early-stage lung adenocarcinoma patients.

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      P1.05-057 - Prediction of Early Recurrence in Patients with Stage I and II Non-Small Cell Lung Cancer Using FDG PET Quantification (ID 4872)

      14:30 - 15:45  |  Author(s): M. Arvanitakis, I.A. Burger, S. Steiger, B. Sick, W. Weder, S. Hillinger

      • Abstract

      Background:
      Although surgical resection remains the optimal treatment for early-stage NSCLC, up to 50% of patients with stage I and II relapse and die within 5 years after curative resection. Therefore prognostic markers are important as these patients might benefit from adjuvant therapy. The goal of this study was to evaluate established PET quantification metrics including: maximal standard uptake volume (SUV~max~), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) as prognostic markers for early recurrence and overall survival in resected early stage lung cancer.

      Methods:
      Between January 2003 and December 2010 182 surgically resected patients with stage I-II NSCLC who underwent 18 F FDG PET/CT less than one month prior to surgery have been evaluated. All patients had at least 5 years of follow-up. Cox proportional hazard model was used to determine the association between variables and survival respectively time to recurrence. For the multivariate analysis the following variables have been included: tumor size on CT, age tumor stage, histology, SUV~max~, TLG (for TLG~42%~ (threshold at 42% SUV~max~) and TLG~2.5 ~(cut-off at SUV 2.5) and MTV~42%~ and MTV~2.5~). To identify high-risk patients we used survival trees.

      Results:
      133 patients were included, 71 with adeno carcinoma, 62 with squamous cell carcinoma. TLG~2.5~ and MTV~2.5~ values have been a significant prognostic factor for recurrence (P<0.0001). Patients with a MTV2.5 above 42 cm[3] had a mean recurrence time of 0.8±0.9 years, while patients with MTV2.5 ≤ 42 cm[3 ]recurred within 2.8±1.3 years. Using the survival tree models TLG~42%~ has been the first choice variable for discriminating high risk patients for DOD (dead of disease) independent from histological type, whereas MTV~2.5~ has been the first choice for DOD in adeno carcinoma patients.

      Conclusion:
      TLG and MTV may be useful prognostic variables in stage I-II NSCLC depending on the tumor type. Using a cut-off at 42 cm[3 ]for early stage adenocarcinoma patients a high risk of recurrence within one year might be identified and adjuvant therapy following surgical resection could improve outcome for those patients.

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      P1.05-058 - Prognostic Factors of Post-Recurrence Survival in Resected Stage I Non-Small Cell Lung Cancer (ID 3819)

      14:30 - 15:45  |  Author(s): Y. Kubouchi, Y. Kidokoro, T. Oono, Y. Yurugi, M. Wakahara, K. Miwa, K. Araki, Y. Taniguchi, H. Nakamura

      • Abstract
      • Slides

      Background:
      Recurrence after surgical resection is a major obstacle in the cure and long term survival, and has become the most common cause of death. However prognostic factors and efficacy of the therapy after recurrence remain controversial. We evaluated the prognostic factors of post-recurrence survival (PRS) in patients of resected stage I NSCLC.

      Methods:
      Of the 551 patients who underwent a complete resection for stage I NSCLC between 2005 and 2013, 89 (16.2%) patients who experienced a postoperative recurrence were selected for this retrospective study. Case of preoperative therapy and death within 30 days of operation were excluded. Clinicopathological factors were analysed for PRS by univariate and multivariate analyses. Univariate and multivariate analyses were performed by using the Cox proportional hazards model.

      Results:
      89 patients experienced recurrence during a median follow-up period of 54.0 months. The median recurrence free interval (RFI) was 16.0 months. The 1-year PRS and 3-year PRS were 65.6% and 44.7%, respectively. The pattern of recurrence was loco-regional in 24(27.0%), and distant in 65(73.0%). The most common organ sites of recurrence were contralateral lung in 42 patients, the ipsilateral thorax in 24, bone in 24, brain in 12, liver in 9. Univariate analysis indicated that male sex (p=0.035), smoking history (p=0.034), larger tumor size over 25mm (p=0.008), stage IB (p=0.044), squamous cell carcinoma (p=0.001), RFI within 16 months (p=0.011), presence of symptoms (p=0.001), bone metastasis (p=0.001), liver metastasis (p=0.009) and not having received any treatment (p<0.001) were significant prognostic factors of worse PRS. Multivariate analysis revealed that larger tumor size over 25mm (p=0.05), RFI within 16 months (p=0.05) and no treatment for recurrence (p<0.001) were the independent prognostic factors for poor PRS. The result of multivariate analysis of PRS determined that post-recurrence therapy had a strong impact on PRS. Therefore, we further examined PRS in 61 patients who underwent any post-recurrence therapy. For patients receiving treatment for recurrence, bone metastasis (p=0.042) was a significant predictive factor of worse PRS, while treatment with EGFR-TKIs (p=0.045) was a good prognostic factor.

      Conclusion:
      This study showed that tumor size, RFI, and post-recurrence therapy were prognostic factors for PRS. In the patients who underwent treatment for recurrence, bone metastasis and treatment with EGFR TKIs were independent prognostic factors. Although further validation is needed, this information is important for future design of clinical trials for therapy after recurrence.

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      P1.05-059 - Factors Associated with Recurrence and Survival in Patients with Curatively Resected Stage IA Adenocarcinoma of the Lung (ID 5990)

      14:30 - 15:45  |  Author(s): M. Harada, H. Horio

      • Abstract

      Background:
      Even when meticulously clinically and pathologically studied, completely resected stage IA adenocarcinoma of the lung does recur. However, there are few data regarding the patterns of recurrences and their risk factors in this population. Therefore, this study characterizes cancer recurrence and its risks and assesses recurrence-free survival in patients with curatively resected stage IA adenocarcinoma.

      Methods:
      Between January 1990 and December 2005, a total of 214 patients were given a final diagnosis of pathologic stage IA (UICC-7) adenocarcinoma of the lung. The medical records of these patients were retrospectively reviewed with regard to patient characteristics, tumor pathologic findings and follow up status. Survival was analyzed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards analysis.

      Results:
      The median follow up after curative resection was 83 months. Cancer recurred in 28 patients (13%). Among them, local recurrence occurred in 10 patients (5%), whereas distant recurrence occurred in18 patients (8%). Recurrence earlier and later than 5 years after surgery was in 15 patients (7%) and in 13 patients (6%), respectively, with nearly constant risk. At 5 years after index resection, 175 patients (82%) were alive without evidence of cancer recurrence, 11 patients (8%) had experienced recurrence of cancer but still alive and 11 patients (5%) had died with non-cancer causes. Recurrence-free 5- and 10-year survival rates were 92.5 and 70.0%, respectively. Univariate analysis revealed five significant prognostic factors: gender (p=0.0177); lepidic component (p =0.0007); tumor location (p=0.0099); pleural invasion (p=0.0274) and lymphatic or vascular vessel invasion (LVI) (p< 0.0001). Multivariate analysis revealed lepidic component, tumor location, and LVI as significant factors. Hazard ratios for recurrence were 0.381 for having lepidic component (95% CI, 0.147-0.979; p= 0.0451), 0.361 for right sided tumor (95% CI, 0.188-0.692; p= 0.0022), and 2.785 for having LVI (95% CI, 1.392-5.555; p= 0.0038).

      Conclusion:
      Surgically “cured” stage IA adenocarcinoma of the lung recurs. Our analyses indicate no-lepidic component, tumor location, LVI as an independent indicator for cancer recurrence. Identifying high-risk patients for recurrence will simplify decision making for postoperative treatment strategies.

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      P1.05-060 - Adherence to Surveillance Guidelines in Resected NSCLC: Physician Compliance and Impact on Outcomes (ID 4624)

      14:30 - 15:45  |  Author(s): C. Ho, J. Siegfried, K. Remo, J. Laskin

      • Abstract

      Background:
      Guidelines on resected NSCLC have varying recommendations on appropriate post-operative surveillance. There is general consensus that patients require follow up q6m with clinic visits or CT scans for the first 2 y. This study evaluated compliance with surveillance guidelines and the impact on outcomes.

      Methods:
      The BC Cancer Agency provides comprehensive cancer control for a population of 4.5 million. Inclusion criteria included referred patients from 2005-2010, resected stage Ib/II NSCLC, minimum 2 y f/u at the BCCA, no prior lung cancer diagnosis. Retrospective chart review collected baseline parameters, follow up visits, CT imaging, recurrence and death.

      Results:
      479 were referred and 263 were eligible. Baseline characteristics median age 68, male 52%, current/former/never smoker 38/52/10%, stage Ib/II 51/49%, squamous/non 30%/70%, wedge/lobectomy/pneumonectomy 8/76/16%, adjuvant chemotherapy 46%. Adherence to 4 interventions in 2 y: clinic visits 62%, CT scans 18%, visit and/or CT 67%. Multivariate analysis (MVA) for predictors of guideline adherence demonstrated only stage was significant. Recurrence rate was 46% at 2 y with patterns of recurrence and treatment in table 1. Surveillance below vs per/above guidelines; PFS 26.6 m vs 22 m (p=0.54), OS 47 m vs 41.8 m (p=0.27).

      Follow up visits and/or CT scans below guidelines n=87 Follow up visits and/or CT scans per or above guidelines n=176 p value
      Recurrence within 2 years 32 (37%) 88 (50%)
      Method of detection 0.41
      Surveillance 18 (56%) 41 (47%)
      Patient 14 (44%) 47 (53%)
      Distribution of recurrence 0.16
      Second primary 1 (3%) 2 (2%)
      Locoregional recurrence only 10 (31%) 14 (16%)
      Metastatic 21 (66%) 73 (82%)
      Curative intent treatment at recurrence 5 (16%) 6 (7%) 0.16
      Palliative chemotherapy 7/27 (26%) 32/82 (39%) 0.25


      Conclusion:
      Compliance with follow up recommendations for resected NSCLC was 67% in our study. Guideline conformity did not increase the rate of curative intent therapy at recurrence due to metastatic presentation nor did it increase the proportion of patients treated with palliative chemotherapy. Better adjuvant treatment and surveillance options need to be developed for resected NSCLC.

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      P1.05-061 - Increased Treatment-Related Toxicity in Patients with Early-Stage Non-Small Cell Lung Cancer and Co-Existing Interstitial Lung Disease (ID 4622)

      14:30 - 15:45  |  Author(s): H. Chen, A.V. Louie, E.J. Nossent, G. Boldt, D. Palma, S. Senan

      • Abstract
      • Slides

      Background:
      Treatment options for early-stage non-small cell lung cancer (ES-NSCLC) are generally well-tolerated. Minimally-invasive surgical techniques, stereotactic ablative radiotherapy (SABR) and radiofrequency ablation (RFA) can all achieve post-treatment mortality of <1% in clinical trial settings. There has been increasing evidence to suggest that patients with interstitial lung disease (ILD) suffer severe toxicity after treatment for NSCLC. Treatment-related toxicity may result in death and may take the form of acute exacerbations of existing ILD following surgery or RFA, or severe radiation pneumonitis following SABR.

      Methods:
      We performed a systematic review of literature in compliance with PRISMA guidelines to investigate the rate of treatment-related toxicity and mortality following treatment for ES-NSCLC. The Medline and EMBASE databases were queried from respective dates of inception to January 2016. Treatment modalities included in the search strategy were surgery, SABR, RFA, particle beam therapy and conventionally-fractionated radiotherapy. Results were summarized with weighted statistics according to the sample size of individual studies.

      Results:
      A total of 3,054 unique records were screened and 282 full texts were reviewed. Forty-nine journal articles were included in the final analysis, with 92% of studies being retrospective in design. Thirty surgical studies with 1716 patients, 13 SABR studies with 122 patients, 3 RFA studies with 46 patients, 2 proton beam therapy (PBT) studies with 17 patients and one carbon ion beam therapy (CIBT) study with 5 patients were included. Most patients in non-surgical studies were medically inoperable. Treatment-related or 30-day post-operative mortality was 2.3%, 15.5%, 8.7%, 5.8% and 0%, respectively, for surgery, SABR, RFA, PBT and CIBT. Treatment-related acute exacerbation of ILD or radiation pneumonitis > grade 3 was 12%, 25%, 25%, 12.5% and 20%, respectively. For patients treated with surgery, 5-year overall survival (OS) was 31.4% to 61.6% (median 54.2%) for patients with ILD and 70.5% to 88.3% (median 83.0%) for patients without ILD. For medically inoperable patients treated with SABR, 2 to 3-year OS was 0% to 53.8% (median 48.8%) for patients with ILD and 54% to 86.7% (median 70.8%) for patients without ILD. Studies that included only patients with idiopathic pulmonary fibrosis reported higher treatment-related toxicity compared to other studies.

      Conclusion:
      An elevated level of treatment-related toxicity is observed in patients treated for ES-NSCLC with co-existing ILD. Medically inoperable patients experienced high levels of treatment-related mortality. For surgery and SABR, overall survival was worse for patients with ILD compared to those without ILD.

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      P1.05-062 - Is Lung Microwave Thermoablation a Valid Alternative to Surgery in High Risk Patients? A Propensity Match Analysis (ID 5648)

      14:30 - 15:45  |  Author(s): P. Mendogni, D. Tosi, A. Palleschi, L. Rosso, I. Righi, M. Montoli, F. Damarco, C. Bareggi, C. Marenghi, M. Nosotti

      • Abstract

      Background:
      Surgery is considered the best treatment in Stage I non small cell lung cancer. Local non–surgical therapies (radiotherapy, thermoablation) are becoming valid alternative to surgery in high risk patients (poor cardiac or pulmonary function, elderly patients).

      Methods:
      Patients submitted in our Department to Microwave thermoablation (MW) were compared with a cohort of patient submitted to lung lobectomy in the same period of time, abstracted from our database with a propensity match method. The study was retrospective on data recorded prospectively. Primary endpoint was overall survival.

      Results:
      From June 2009 to October 2014 in our Department, 36 patients underwent MW for Stage I non-small cell lung cancer (NSCLC) or lung metastasis. From our database were abstracted 41 patients with a propensity match method, submitted to lung lobectomy. Two groups were comparable by age, diagnosis, stage and gender. MW group resulted elder than Surgery group (75,5 vs 72,2 years; p<0,001). Lesion diameter was greater in MW group (20,9 vs 26,5 cm; p<0,001). Overall survival, analyzed by actuarial survival curve, was comparable (Logrank test p=0,2).

      Conclusion:
      In our experience, in a propensity match evaluation, lung MW thermoablation resulted non inferior than lung lobectomy in terms of overall survival. Even though surgery is still considered the first choice in patients affected by Stage I NSCLC or lung metastasis, lung MW thermoablation is confirmed as a valid alternative treatment in high risk patients. Randomized prospective studies are mandatory.

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      P1.05-063 - Multicenter Observational Study of Patients with Resected Early-Staged NSCLC, Who Were Excluded from an Adjuvant Chemotherapy Trial (ID 4713)

      14:30 - 15:45  |  Author(s): T. Hishida, M. Tsuboi, K. Yoh, K. Takamochi, H. Sakurai, Y. Goto, T. Shukuya, Y. Ohashi, H. Kunitoh

      • Abstract
      • Slides

      Background:
      From Nov. 2008 to Dec. 2013, the Japan Clinical Oncology Group (JCOG) conducted a randomized phase III trial (JCOG0707), which compared the survival benefit of UFT and S-1 for completely resected pathological (p-) stage I (T1>2 cm and T2 in the 6th TNM classification) NSCLC and a total of 963 patients were enrolled. Recently, there is a growing concern that those who participated in clinical trials are highly selected and do not represent the “real-world” population. Hereby, we conducted a multicenter observational study of patients excluded from JCOG0707 trial during the study period.

      Methods:
      We retrospectively collected and analyzed the patients’ backgrounds, tumor profiles, post-surgical treatment of the patients who underwent R0 resection of p-stage I (T1>2cm and T2 in TNM 6th) NSCLC by lobectomy or larger lung resection but were excluded from JCOG0707 from Japanese multi-centers.

      Results:
      Of the 48 institutions which took part in JCOG0707, 34 (enrolling 917 or 95.2% of all JCOG0707 patients) participated in this multicenter study, and 5006 patients were enrolled. Among them, 2617 (52.3%) patients fulfilled the eligibility criteria, but were not enrolled to JCOG0707 mainly due to patients’ decline (69.2%), or physicians’ discretion (20.5%). The accrual rate to JCOG0707 was various by institutions (4.1 to 46.1%), but was 25.9% (917 / [917+2617]) as a whole. Total number of p-stage I and eligible patients at each institution did not correlate the accrual rate (R2=0.003 and 0.046). In the remaining 2389 (47.7%) patients, main ineligible reasons included the existence of active multiple cancer (29.1%), physicians’ decision based on the patients’ comorbidities (19.4%), delayed recovery from surgery (14.1%), and high age ≥81 years (10.7%). Majority of patients received no adjuvant chemotherapy (n = 3338, 66.7%). This proportion differed according to p-T factor (T1: 75.3% vs. T2 : 57.8%, p<0.001) and the JCOG0707 eligibility (ineligible population: 77.6% vs. eligible population: 56.7%, p<0.001). Standard UFT and experimental S-1 were given in 1550 (31.0%) and 21 (0.4%) patients, respectively. Among those who received adjuvant UFT, 971 (62.6%) took UFT for one year or longer.

      Conclusion:
      Only selected population of candidate patients, even if they met the eligibility criteria, were enrolled to JCOG0707 adjuvant chemotherapy trial for early-stage NSCLC. The “excluded” patients were mainly treated with observation alone or standard UFT treatment. Further analysis of this “excluded” population, including long-term survival, should be necessary for external validation of the randomized trial results.

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      • Abstract

      Background:
      Multifocal lung cancer (MFLC) is a clinical scenario that is more frequently diagnosed with the increased utilization of computed tomography of the chest. The management of MFLC is limited by the difficulties in accurately staging a patient and understanding whether lesions represent separate primaries or metastatic disease. We sought to understand the global practice patterns of MFLC.

      Methods:
      A questionnaire was developed and sent to members of the International Association for the Study of Lung Cancer through REDCap electronic data capture tools to assess how a hypothetical patient with synchronous MFLC would be evaluated and treated. Responses were compared by specialty using the χ[2] test.

      Results:
      We received 221 responses from multiple specialists (74 Thoracic Surgeons, 68 Medical Oncologists, 32 Pulmonologists, 22 Radiation Oncologists and 25 others) primarily from Europe (n=76) and North America (n=62). Over 87 respondents reported 20 or more years of experience in the field. Most respondents recommended surgery (n=140, 63%), but many others did not (n=39, 18%) or were uncertain (42, 19%). Surgeons (n=60/74, 81%) were significantly more likely to recommend surgery than medical oncologists (n=37/68, 54%), pulmonologists (n=21/32, 66%) or radiation oncologists (n=10/22, 45%; p=0.01). Lobectomy of the primarily involved lobe (n=42, 30%) and various combinations of segmentectomies (n=48, 34%) were the most commonly recommended surgical approaches. Of those who recommended surgery, most would obtain a PET/CT to rule out distant metastasis (n=135, 97%) and an MRI to rule out brain metastases (n=76, 55%) but in the absence of radiographic lymph node involvement most would not stage the mediastinum by bronchoscopy or mediastinoscopy prior to resection (n=90, 65%). Many preferred obtaining multiple biopsies of separate lesions (n=139, 63%) and genetic testing of these lesions (n=146, 66%) to assess their histologic and genetic agreement. In the case that surgery was not offered or declined, more respondents recommended radiation (n=114, 52%) than those who did not (n=50, 23%) or were uncertain (56, 26%). Similarly, in the absence of surgery or radiotherapy, slightly more respondents recommended systemic chemotherapy (n=83, 38%) than those who did not (n=79, 36%) or those who were uncertain (n=59, 27%).

      Conclusion:
      Although most respondents favored surgery when feasible for MFLC, many were uncertain as to the optimal approach for this disease. Optimal management of MFLC requires greater evidence from studies which is currently lacking, and current strategies are strongly influenced by specialty bias.

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      P1.05-065 - Usage of Chest Radiography or Computed Tomography in Post-Treatment Surveillance for Stage I and II NSCLC: Influence on Survival (ID 5524)

      14:30 - 15:45  |  Author(s): L. Alberts, R. Karzijn, F.N. Hofman, S.Y. El Sharouni, E.A. Kastelijn, F.M.N.H. Schramel

      • Abstract

      Background:
      Survivors of stage I and II non-small-cell lung cancer (NSCLC) have higher risk of developing a recurrence of disease or a second primary lung cancer compared to the general population. Post-treatment surveillance (visits and radiological imaging) is needed for early recognition. Although a myriad of international guidelines exist regarding post-treatment surveillance no consensus has derived yet. The aim of this study was to further establish the appropriate follow-up modality: chest radiography with or without a computed tomography (CT) scan.

      Methods:
      In this retrospective study all patients diagnosed with a recurrence of previously treated stage I and II NSCLC between 2008 and 2014 at St Antonius Hospital, Nieuwegein the Netherlands, were included. We categorized patients after treatment in two imaging modality groups: one group received only chest radiographs (CR group) and the other group received ≥ one thoracic CT scan (CT group). The overall survival (OS), 1- and 3-yearssurvival and progression free survival (PFS) were compared between the groups by using the Kaplan-Meier survival, the log rank-test and the Cox proportional hazard model.

      Results:
      73 patients were enrolled; 50 patients in the CR group and 23 patients in the CT group. The median overall survival was 22.1 months (interquartile range (IQR) = 14.2-39.2 months) in the CR group compared to 27.2 months (IQR= 18.5-53.2 months) in the CT group (p = 0.12). After adjustment for the Eastern Cooperative Oncology Group (ECOG) performance score and morphology was made, both the overall survival (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 0.76-2.70, p = 0.27) and the progression free survival (HR = 1.16, 95% CI = 0.65 – 2.07, p = 0.63) were not different in the CR group compared to patients in the CT group. There was no significant difference in the 1- and 3-yearssurvival either. The 1-yearssurvival was 80% in the CR group versus 91% in the CT group (HR = 5.50, 95% CI = 0.52-58.01, p = 0.16) and the 3-yearssurvival was 30% versus 39% (HR = 1.50, 95% CI = 0.74-3.01, p = 0.29).

      Conclusion:
      We showed that follow-up with a chest radiography, in patients with earlier diagnosed and curative treated stage I and II NSCLC, did not give inferior clinical outcomes compared to follow-up with a CT scan. Although more investigation is needed, this study might indicate that there is no need for a CT scan as standardized follow-up.

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      P1.05-066 - Impact of Micropapillary Pattern in Nodal Upstaging of Lung Adenocarcinoma 2cm or Less (ID 5189)

      14:30 - 15:45  |  Author(s): H. Yamazaki, Y. Kondo, M. Naito, H. Nakashima, Y. Matsui, K. Shiomi, Y. Satoh

      • Abstract

      Background:
      Clinical and pathological determinations of lymph node staging are critical in the treatment of lung cancer. However, upstaging of nodal status frequently is necessitated by postoperative findings. It is now being recognized that lung adenocarcinoma (LAC) with tumor cells arranged in a micropapillary pattern (MPP) is more malignant than those without such pattern. Thus, this study was conducted to evaluate clinicopathologic features that impact nodal upstaging in patients with small-sized(≦2cm) LACs with MPP(LAC-MPP).

      Methods:
      We retrospectively reviewed the 182 radically resected lung adenocarcinomas at the Kitasato University Hospital, Japan, from January 2005 to December 2015. MPP was defined as a small papillary tumor cell tuft without an obvious fibrovascular core. Tumors with ≧1% of their tumor cells arranged in a MPP were diagnosed as LAC-MPP, while the remainders were diagnosed as conventional LAC. The histological subtypes and differentiation grade of LAC were determined according to the 4th WHO classification. The registry date of the patients with LAC and LAC-MPP were analyzed, and the clinicopathologic profiles and surgical outcomes of the patients were evaluated.

      Results:
      One hundred and sixty (88%) of the total 182 were LAC whereas 22(12%) were LAC-MPP. Among the two groups, there is no significant difference in age, sex, smoking habit, preoperative serum CEA level, or surgical procedures. Compared with the LAC, the LAC-MPP had worse statuses for lymphatic invasion (p=0.0096), pleural invasion (p=0.002), postoperative lymph node metastases (p<0.001) and postoperative recurrence (p=0.002). On the other hand in clinical stages, pleural lavage cytology, and postoperative stages, there is not significant deference statistically. Median follow up time was 48 months. The five-year overall survival rates were 92% in LAC group and 85% in LAC-MPP, statistically not significant deference (p=0.98). Also with regarding to the median relapse free survival rates, no significant difference was found between two groups (p=0.14).

      Conclusion:
      The follow-up term of patients was limited in this study. But, we concluded that LAC-MPP should be considered as an aggressive disease showing nodal upstage. Although lymph node metastasis and lymphatic infiltration should be usually reported in LAC-MPP patients, these are difficult to detect by preoperative imaging tools such as CT and PET canning. Therefore, MPP could be important factor to determine the indications for limited resection for LAC patients even if small-sized(≦2cm) LAC- MPP.

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      P1.05-067 - Consultation with Medical Oncology Less Common in Elderly Patients with Resected Stage II Nonsmall Cell Lung Cancer (ID 4679)

      14:30 - 15:45  |  Author(s): S. Li, G. Darling, A. Farrelly, K. Forster, K. Woltman, J. Stiff, W. Evans

      • Abstract

      Background:
      Adjuvant chemotherapy (AC) is guideline recommended standard of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a significant survival benefit, uptake of AC has been lower than expected and has remained unchanged since 2008 at 50-55%. Factors that may preclude use of chemotherapy include comorbid medical conditions, socioeconomic and demographic factors and the opportunity for consultation with a medical oncologist (MO). This study evaluated: 1) patient opportunity for a consultation with a MO, and 2) differences between patients who had a consultation and those who did not.

      Methods:
      Stage II NSCLC adult patients diagnosed between 2010 and 2013 were identified using the Ontario Cancer Registry. Complete surgical resections and consultation with a MO were identified using multiple administrative databases. Receipt of guideline-recommended AC within 120 days after resection, and consultation with MO within 30 days prior and 90 days after resection were determined. Guideline-recommended AC includes platinum based regimens, including receipt outside a Regional Cancer Center (RCC). Alternative treatments were defined as non-platinum based chemotherapy or radiotherapy. Socioeconomic and demographic characteristics were compared between patients who received a consultation and those who did not. Characteristics associated with receiving a consultation were assessed using univariable analysis and multivariable logistic regression.

      Results:
      Of 778 Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318, CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40) received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56) of patients did not have systemic treatment after surgery. Overall, 72.9% (n=567) of patients had a consultation with a MO within 30 days prior or 90 days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had a MO consultation. Median time from resection to consultation was 29 days, and did not differ between treatment groups (p=0.35). Age was a significant determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more likely to have a consultation versus patients >80 yrs. Other characteristics were not significantly associated with having a consultation.

      Conclusion:
      Although uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-55.62), the majority of patients had an opportunity to discuss this treatment option with a MO. Patients over 80yrs were significantly less likely to have this consultation.

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      P1.05-068 - Elderly Patients with Resected Stage II Nonsmall Cell Lung Cancer Are Less Likely to Have a Consultation with a Medical Oncologist (ID 4814)

      14:30 - 15:45  |  Author(s): G. Darling, S.X.L. Li, A. Farrelly, K. Forster, K. Wortman, J. Stiff, W.K. Evans

      • Abstract
      • Slides

      Background:
      Adjuvant chemotherapy (AC) is guideline recommended standard of care for resected Stage II NSCLC patients in Ontario. Despite evidence of a significant survival benefit, uptake of AC has been lower than expected and has remained unchanged since 2008 at 50-55%. Factors that may preclude use of chemotherapy include comorbid medical conditions, socioeconomic and demographic factors and the opportunity for consultation with a medical oncologist (MO). This study evaluated: 1) patient opportunity for a consultation with a MO, and 2) differences between patients who had a consultation and those who did not

      Methods:
      Stage II NSCLC adult patients diagnosed between 2010 and 2013 were identified using the Ontario Cancer Registry. Complete surgical resections and consultation with a MO were identified using multiple administrative databases. Receipt of guideline-recommended AC within 120 days after resection, and consultation with MO within 30 days prior and 90 days after resection were determined. Guideline-recommended AC includes platinum based regimens, including receipt outside a Regional Cancer Center (RCC). Alternative treatments were defined as non-platinum based chemotherapy or radiotherapy. Socioeconomic and demographic characteristics were compared between patients who received a consultation and those who did not. Characteristics associated with receiving a consultation were assessed using univariable analysis and multivariable logistic regression.

      Results:
      Of 778 Stage II resected NSCLC patients who survived at least 120 days, 40.9% (n=318, CI: 37.40–44.42) received guideline-recommended AC, 3.0% (n=23, CI: 1.70-4.40) received alternative treatment in an RCC, 11.2% (n=87, CI:8.95-13.50) received chemotherapy outside of an RCC hospital, and 45.0% (n=350, CI:41.45-48.56) of patients did not have systemic treatment after surgery. Overall, 72.9% (n=567) of patients had a consultation with a MO within 30 days prior or 90 days after resection. Of 350 patients who did not receive AC, 219 (62.6%) had a MO consultation. Median time from resection to consultation was 29 days, and did not differ between treatment groups (p=0.35). Age was a significant determinant for MO consultation. Adjusting for sex, patients aged 41-60yrs (OR 2.38, CI:1.25-4.56) and 61-70yrs (OR 2.46, CI:1.35-4.49) were significantly more likely to have a consultation versus patients >80 yrs. Other characteristics were not significantly associated with having a consultation.

      Conclusion:
      Although uptake of guideline-recommended AC is lower than expected (52.1%, CI:48.48-55.62), the majority of patients had an opportunity to discuss this treatment option with a MO. Patients over 80yrs were significantly less likely to have this consultation.

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      P1.05-069 - Stage II NSCLC Treated with Non-Surgical Approaches: A Multi-Institution Report of Outcomes (ID 4552)

      14:30 - 15:45  |  Author(s): S. Dudani, X. Zhu, D.W. Yokom, A. Yamada, C. Ho, J. Pantarotto, N.B. Leighl, T. Zhang, P. Wheatley-Price

      • Abstract
      • Slides

      Background:
      Standard management of stage II non-small cell lung cancer (NSCLC) is surgery, often followed by adjuvant chemotherapy. However, some patients do not undergo surgery for various reasons. The optimal non-surgical management of stage II NSCLC is undefined, with a paucity of data to guide decision making in this setting. We examined outcomes of stage II NSCLC patients who were treated with curative, non-surgical approaches.

      Methods:
      We performed a multi-institution review of stage II NSCLC patients treated non-surgically with curative intent between January 2002 and December 2012, across three major Canadian academic cancer centres. Data on demographics, comorbidities, staging, treatment, and outcome were collected. The primary endpoint was overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for factors associated with choice of therapy and OS.

      Results:
      158 patients were included for analysis. Median age 74 years (range 50-91); 44% female; 94% current/former smokers; 67% performance status (PS) 0-1. Stage II groupings: T2b-T3 N0 in 55%; N1 in 45%. The commonest reasons for no surgery were inadequate pulmonary reserve (27%) and medical comorbidities (24%). All patients received radical radiotherapy (RT) (median 60 Gy [range 48-75]). 73% received RT alone; 24% and 3% of patients received concurrent and sequential chemoradiotherapy (CRT), respectively. Of those who received RT only, 39% received conventional (1.8-2 Gy/day), 51% received hypofractionated (2.5-4 Gy/day) and 10% received stereotactic body RT (≥7.5 Gy/day). In multivariate analyses, CRT was less likely in patients ≥70 years old (OR 0.28, 95% CI 0.11-0.70, p=0.006), as well as in those with higher (>5) Charlson comorbidity scores (OR 0.34, 95% CI 0.13-0.90, p=0.03) or low (<10x10[9]/L) white blood cell (WBC) counts (OR 0.26, 95% CI 0.09-0.73, p=0.01). At time of analysis, 74% have died. Median OS was 22.9 months (95% CI 17.1-26.6 months). Patients receiving CRT had significantly longer median OS than those receiving RT alone (39.1 vs 20.5 months, p=0.0019). RT fractionation schedule (p=0.16) and nodal status (p=0.14) did not influence survival. After adjusting for possible confounders, treatment with CRT was associated with improved survival (HR 0.38, 95% CI 0.21-0.69, p=0.001), while elevated WBC (HR 2.45, 95% CI 1.48-4.04, p=0.0005) and poor PS (ECOG 2-3) (HR 1.87, 95% CI 1.16-3.01, p=0.01) were poor prognostic factors.

      Conclusion:
      Non-surgical approaches to management of stage II NSCLC are varied. Treatment with CRT was associated with significantly longer survival compared to RT alone, and a randomized trial may be warranted in this population.

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      P1.05-070 - Diagnostic Yield and Efficacy of EBUS TBNA in Molecular Testing for NSCLC Mutations (ID 4401)

      14:30 - 15:45  |  Author(s): S. Nuguru, S. Raad, E. Bendaly, H. Oueini, K. Diab

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) can be further defined at the molecular level by recurrent driver mutations including ALK, BRAF, EGFR, HER2, KRAS, MEK1, MET, NRAS, PIK3CA, RET, and ROS1. Genetic testing has become a routine part of diagnosis and staging for patients with NSCLC. The presence of mutations can influence response to targeted therapy; tailoring therapy accordingly has become standard practice.

      Methods:
      Sixty-nine patients referred to Indiana University Hospital with suspected or confirmed lung adenocarcinoma underwent EBUS-TBNA of lung masses or lymph nodes using a 21-gauge Olympus[TM] needle without suction. Samples were first reviewed by a pathologist, and if suspicious for NSCLC, were sent for different types of molecular testing based on the clinical scenario. At least 6 extra passes were placed in cell block. For Paradigm testing, 10 passes were sent. EGFR and KRAS testing were performed using the FDA approved Thera screen RGQ PCR Kit. Testing for ALK rearrangement was done using fluorescent in situ hybridization. In some cases, testing for these mutations in addition to ROS1, BRAF, and HER2 was done using the Paradigm Cancer Diagnostics test.

      Results:
      Sixty-nine samples from patients with NSCLC obtained by EBUS-TBNA were sent for molecular testing for EGFR. All samples were sufficient for analysis (Yield=100%). EGFR mutations were found in 3 patients (4.3%) vs. 66 wild-type (95.7%). 60 samples were sent for molecular testing for KRAS (yield = 100%), of which 10 had mutations (16.7%) vs. 50 wild-type (83.3%). 51 samples were sent for ROS1 testing (0 mutant, 48 wild-type); tissue samples were inadequate for testing in 3 patients (yield=94.1%). 64 samples were sent for ALK testing (3 (4.7%) mutant, 55 (85.9%) wild-type; yield = 90.6%). Ten samples were sent for BRAF testing and two samples were sent for HER2 testing, all of which were negative for mutations (yield = 100%). No complications were associated with EBUS TBNA.

      Conclusion:
      EBUS TBNA with a 21-gauge needle is a safe and efficient method for molecular mutational analysis in patients with NSCLC. It can be used effectively for diagnosis, staging and guiding treatment decisions for NCSLC. Adequate samples for mutational analysis can be obtained and placed in cell block without suction. Improving the yield of this technique and comparing the yield with and without suction is important as we start testing for a greater number of mutations.

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      P1.05-071 - A Review of Quality of Life Measures Used in Lung Cancer Surgical Outcomes (ID 6175)

      14:30 - 15:45  |  Author(s): R. Yip, E. Taioli, R. Schwartz, K. Li, K. Tam, Y.M. Htwe, D.F. Yankelevitz, C.I. Henschke

      • Abstract

      Background:
      With the increased life expectancy following surgery for early stage non-small-cell lung cancer (NSCLC), concern about the quality of life (QoL) of patients after surgery has gained attention. Previous QoL studies were limited by small sample size, inclusion of late-stage cancers and non-surgical treatments. This review summarized the existing literature on QoL in early stage lung cancer patients who underwent surgical treatment.

      Methods:
      PubMed and PsycINFO were searched for articles published between 1995 (year of the last published meta-analysis) and March 21, 2016. All English articles reported on quality of life for Stage I NSCLC were included. Data extraction was performed by two independent reviewers using pre-specified criteria.

      Results:
      Ten articles from nine studies were identified. Of the nine studies, four reported on the SF-36, one on the SF-12, one on the EORTC QLQ-C30, one on POMS-TMD, one on EQ-5D, and one on SGRQ. One study reported only on pre-surgical QoL, six only on post-surgical QoL and two studies reported on both pre- and post- surgical QoL. Timing for the administration of post-surgical QoL survey varied, from time at discharge to up to six years post-surgery. Two studies included only NSCLC patients with COPD. Due to the heterogeneity of these studies, comparison between studies and traditional meta-analysis were not possible.

      Conclusion:
      The literature on QoL in Stage I NSCLC patients is very sparse. As CT screening for lung cancer becomes more widespread with a consequent shift from late to early stage NSCLC, additional research is needed to explore the impact of different NSCLC surgical approaches on QoL.

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      P1.05-072 - Predictors and Patterns of Lymph Node Metastasis in Small Peripheral Non Small Cell Lung Cancer (ID 4268)

      14:30 - 15:45  |  Author(s): J. Lin, X. Yang, L. Yan, S. Wang, W. Zhong, Q. Nie, R. Liao, S. Dong, B. Jiang, Y.-. Wu

      • Abstract
      • Slides

      Background:
      Lobectomy is the standard treatment of early stage non-small cell lung cancer (NSCLC) and wheather sublobar resection is appropriate for small peripheral small NSCLC or not is unclear. PET-CT is a powerful imaging modality for the detection of lymph node metastasis with a relatively low false-negative rate. We identified predictors and patterns to identify false-negative N(+) disease in PET-CT.

      Methods:
      A total of 435 consecutive cN0 peripheral NSCLC underwent curative-intent resections following PET-CT scans from January 2008 to December 2014 in our hospital, we analysed patients’ clinicopathological data retrospectively. 171 patients with tumour size≤2cm were enrolled to identify predictors and patterns of lymph node metastases by multivariable analysis. The cut‑off values, sensitivity and specificity for the predictors were calculated using a receiver operating characteristic curve. The patterns of lymph node metastases were also analysed.

      Results:
      In total, 9.4% (16/171) PET-CT-diagnosed N0 NSCLC cases were pathologically N1/N2 disease. The preoperative CEA was a unique independent risk factor for lymph node metastasis (OR = 0.914, 95 CI% = 0.85–0.98, P = 0.009). According to ROC curve, we divided the patients into two groups by CEA: the N(+) rates in the CEA ≤1.67 and CEA> 1.67 groups were 1.6% (1/64) and 14.0% (15/107), respectively (P =0.007). In 16 patients with lymph node metastasis, 7 were N1 disease, and 6 out of 9 N2 diseases were skip N2 disease. 93.5%(15/16) lymph node metastases were found in adenocarcinoma and 11 of them were single station metastases. The metastases rates in solid and subsolid lesions were 12.8%(16/125) and 0%(0/46)(P=0.007), retrospectively. Solid/mucinous/ micropapillary predominant adenocarcinoma were associated with LN metastases(31.2% vs 7.1%, P=0.01).

      Conclusion:
      The preoperative CEA was an independent risk factor for lymph node metastases in cN0 NSCLC with T ≤ 2cm. In patients with CEA>1.67, sublobar resection should be avoided before thorough lymph node sampling that include intrapulmonary lymph node while patients with CEA ≤ 1.67 may be candidate for sublobar resection, especially in GGO lesions. In patients with solid/mucinous/ micropapillary predominant adenocarcinoma, sublobar resection should be avoided due to high LN metastases rate.

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      P1.05-073 - Evaluation of Stage 1 Sub-Solid Lung Nodules Using PET Imaging (ID 4287)

      14:30 - 15:45  |  Author(s): B.V. Tran, D.G. Nicastri, R. Yip, K. Li, D. Xu, M.B. Beasley, M. Salvatore, D.F. Yankelevitz, C.I. Henschke, R. Flores

      • Abstract

      Background:
      Positron emission tomography (PET) scans are valuable in the evaluation of lung nodules. Subsolid (SS:<80% solid) lung nodules, however, often have low levels of metabolic activity and rare metastases. The purpose is to assess PET in the evaluation of SS nodules.

      Methods:
      Between 2009-2015, 892 patients had a chest computed tomography (CT) with a SS finding and PET within 6 months, with pathology specimen, at our institution. 50 patients had clinical stage IA/B lung cancer and were retrospectively analyzed. CT analysis further classified these subsolid lesions as nonsolid(NS) and part-solid(PS).

      Results:
      26 patients had NS nodules and 24 PS. Mean maximal tumor dimension was not statistically significantly different between the groups (mean±SD; NS- 16.8±6.9; PS- 16.9±6.2). PET positive nodules (SUV>2.5) were larger in maximal tumor dimension than PET negative on CT though the difference was not statistically significant (mean±SD; PET Neg, n=42- 16.1±5.7; PET-pos, n=8- 20.9±8.8). Among the 39 patients in which lymph node pathology was obtained, sensitivity and specificity of PET in identifying N1 disease was 0% and 92.9%; and 0% and 100% for N2 disease. Recurrence and overall survival were 0% and 100%, with median follow-up of 34 months. Figure 1



      Conclusion:
      The use of PET for the evaluation of SS nodules in stage I lung cancer may have limited value in detecting metastases and affecting current clinical decision making for these patients.

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      P1.05-074 - Factors Predicting Discordance between Clinical and Surgical-Pathologic Staging in Operable Non-Small Cell Lung Cancer (ID 4083)

      14:30 - 15:45  |  Author(s): I. Koukis, D. Grapsa, P. Tomos, A. Papazafiropoulou, A. Karakatsani, I. Kotteas, A. Charpidou, K. Syrigos

      • Abstract
      • Slides

      Background:
      Accurate clinical staging is of the utmost importance for the optimal management of patients with non-small cell lung cancer (NSCLC). The aim of this study was to identify factors associated with discordance between clinical and pathologic staging in patients with operable NSCLC.

      Methods:
      The medical records of 85 patients with early-stage NSCLC, who had been submitted to thoracotomy followed by surgical resection of the primary tumor and systematic lymph node dissection, were retrospectively reviewed. All patients were staged according to the 7th edition of the TNM staging system. The presence of postoperative upstaging or downstaging was correlated with various demographic and clinicopathological factors, including age, sex, smoking history, tumor histology, tumor size and location.

      Results:
      Discordance between clinical and surgical-pathologic staging was found in 45/85 cases (52.9%), and the majority of these patients were upstaged (35/85 cases, 41.2%). Patients with IIB and IB clinical stage had the highest (77.8%) and lowest (48.1%) probability of discordance, respectively. With regard to T stage, disagreement between clinical and surgical-pathologic T stage was noted in 22/85 patients (25.9%), including 16 upstaged patients (16/85, 18.8%) and 6 downstaged patients (6/85, 7.1%). Nodal status was altered postoperatively in 39/85 cases (45.9%), including 29 upstaged patients (29/85, 34.1%) and 10 downstaged patients (10/85, 11.8%). The rate of unsuspected mediastinal lymph node involvement (pathologic stage N2) was 14.1% (12/85 patients), despite negative mediastinoscopy findings. Age was the only statistically significant factor independently associated with staging discordance (odds ratio 0.93; 95% confidence interval, 0.87 to 0.99).

      Conclusion:
      Postoperative upstaging or downstaging was observed in a relatively high percentage of our patient population, and was significantly and independently correlated with patient’s age. These observations warrant confirmation in larger prospective series of patients with early-stage NSCLC.

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      P1.05-075 - The Correlation between the Prognoses of Patients with Non-Small Cell Lung Cancer and Preoperative Platelet- Lymphocyte Ratio (ID 5137)

      14:30 - 15:45  |  Author(s): S. Ishihara, M. Shimomura

      • Abstract
      • Slides

      Background:
      The platelet- lymphocyte ratio (PLR) is a prognostic factor that correlates immunity or inflammation with tumor invasion. We retrospectively investigated the correlation between prognosis and preoperative PLR in patients with non-small cell lung cancer who underwent anatomical lung resection in our hospital.

      Methods:
      We conducted a retrospective study of 116 patients with primary lung cancer who underwent anatomical lung resection in our hospital from January 2009 to May 2014. We excluded patients who underwent previous lung resection or had intraoperative malignant pleural effusion or positive surgical margins. We analyzed 105 patients (65 with adenocarcinoma, 25 with squamous cell carcinoma, 9 with large cell carcinoma, and 2 with adenosquamous carcinoma). We constructed a ROC curve with PLR values calculated preoperative blood analyses and determined that the threshold was 160. We divided the patients into high and low PLR groups. We analyzed these two groups with respect to background, pathological findings, and cancer-specific survival. Additionally, we investigated factors that correlated with cancer-specific survival with.

      Results:
      The median patient age was 71 years (range, 50-88 years). There were 75 male patients and 25 female patients. The median follow-up duration was 43 months (range, 0-85 months). Regarding surgical techniques, 101 patients underwent lobectomy, 3 underwent segmentectomy, and 1 patient underwent sleeve lobectomy. A total of 47, 34, 8, 9, 6, and 1 patients were diagnosed with pathological stage IA, IB, IIA, IIB, IIIA, and IIIB cancer. The overall survival rate was 71.3%. When examining background characteristics, tumor size was larger and T factor was more elevated in the high PLR groups, and pathological stage was more advanced in the high PLR group. N factor was not significantly different between the two groups. Cancer-specific survival was significantly poorer in the high PLR group than in the low group (p=0.0007). Considering tumor types, patients with adenocarcinoma in the high PLR group had poorer prognosis compared to the patients with adenocarcinoma in the low PLR group (p=0.0002), but for squamous cell carcinoma and in the other tumor types, there was no significant difference (p=0.20 and p=0.86, respectively). Multivariate analysis revealed that PLR was an independent prognosis factor for the cancer-specific survival.

      Conclusion:
      In the patients who underwent anatomical resection with lung cancer, PLR was correlated with prognosis.

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      P1.05-076 - Risk Factors in Patients with Pathological Stage I Non-Small Cell Lung Cancer (ID 4256)

      14:30 - 15:45  |  Author(s): Y. Tokunaga, T. Okamoto, S.S. Chang

      • Abstract

      Background:
      Patients with pathological (p-) stage I non-small cell lung cancer (NSCLC) can have good prognosis with complete resection, whereas some patients die from disease recurrence. The aim of this study was to investigate the risk factors for p-stage I NSCLC.

      Methods:
      We retrospectively reviewed 234 patients with completely resected p-stage I NSCLC from March 2005 to December 2015. Patients with synchronous or metachronous multiple lung cancer or malignancies from other organs were excluded. Clinicopathological factors were analyzed, including age, sex, serum carcinoembryonic antigen (CEA) levels, histology, surgical procedure, tumor size, pleural invasion, lymphatic invasion, vascular invasion, and histological grade. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed.

      Results:
      The study group included a total 234 patients, with 119 men and 115 women, ranging in age from 22 to 88 years (mean 68±10.4 years). The median follow-up period was 50.7 months. The preoperative serum CEA level was elevated in 37 patients. Complete resection was performed in all patients, comprising pneumonectomy in one patient, and bilobectomy in two, lobectomy in 192, segmentectomy in 17, and wedge resection in 22. Adenocarcinoma, squamous cell carcinoma, and other histology were observed in 187, 38 and nine patients, respectively. The maximum tumor diameter exceeded 30 mm in 63 patients and tumor diameter was 30 mm or less in 171 patients. There were 38 patients with pleural invasion, 24 patients with lymphatic invasion, and 34 patients with vascular invasion. Multivariate analysis showed that pleural invasion and lymphatic invasion were independent factors for recurrence, whereas older age (>70 years), high serum CEA levels, pleural invasion, lymphatic invasion and vascular invasion were independent factors for poor survival. The 5-year DFS and OS in patients without pleural invasion and without lymphatic invasion were 88.5% and 93.5%, respectively, compared with 29.1% and 33.2% in patients with pleural invasion and with lymphatic invasion (p < 0.001).

      Conclusion:
      Pleural invasion and lymphatic invasion were independent factors for recurrence and poor survival in p-stage I NSCLC. Adjuvant chemotherapy should be considered for patients with lymphatic invasion.

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      P1.05-077 - Outcome of N2 Disease in NSCLC - A Single Institution Experience (ID 5041)

      14:30 - 15:45  |  Author(s): L. Bitar, F. Seiwerth, I. Markelić, M. Koršić, S. Pleština, B. Čučević, S. Kukulj, M. Roglić, M. Samarzija, M. Jakopović

      • Abstract

      Background:
      There are many different therapy options available for stage IIIA-N2 NSCLC patients that were set by the NCCN guidelines. That is why we decided to evaluate outcome of different management strategies.

      Methods:
      Medical records of the patients diagnosed with lung cancer in Clinical hospital center Zagreb, Department for respiratory diseases Jordanovac during the year 2012 and 2013 were retrospectively collected and reviewed. Median overall survival (mOS) was measured and analyzed using the Kaplan-Meier and log-rank test.

      Results:
      There were 147 patients diagnosed with stage IIIA–N2 NSCLC, out of which 105 were male (71.4%), with median age 63 (40-102). Most of them were ex-smokers (54.4%), while only 9.5% never smoked cigarettes. Most of them had very good performance status at the time of diagnosis (ECOG 0-1 91.9%). 78 (53.1%) of the patients were diagnosed with adenocarcinoma, 62 (42.2%) with planocellular carcinoma, 6 (4.1%) with NSCLC-NOS and only 1 (0.7%) with adenosquamous carcinoma. mOS for all diagnosed lung cancer patients was 9 months and for NSCLC 8 months. mOS for IIIA-N2 NSCLC was 14 months. Our patients were treated with chemotherapy in 40.8% of the cases (mOS 11 months); sequential chemotherapy and irradiation in 25.2% (mOS 17 months); surgery, sequential chemotherapy and irradiation in 14.3% (mOS 26 months); surgery and adjuvant chemotherapy in 4.1% (mOS 15 months) and neoadjuvant chemotherapy and surgery in 1.4% (mOS 34 months) of the cases, while only 1.4% of all patients were treated with only surgical resection (mOS 4 months); (p=0.001).

      Conclusion:
      We analyzed the data collected at our department to assess the difference in outcomes of different strategies in IIIA – N2 management. The most of our patients were treated with platinum-based doublets only, followed by sequential chemotherapy and irradiation as a second most frequent therapy option. Only 21.8% of the patients were treated with surgery only or surgery combined with other forms of treatment. Only 1 patient underwent concurrent chemoradiation. The difference in overall survival between different therapy options showed highest mOS in patients treated with neoadjuvant chemotherapy and surgery followed by surgery and sequential chemotherapy and irradiation. Sequential chemotherapy and irradiation was superior to chemotherapy. The limitation of our study was a small number of patients in this specific subgroup, as well as small number of patients who underwent concurrent chemoradiation.

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      P1.05-078 - The Relationship between IASLC/ATS/ERS Grading System of Adenocarcinoma of the Lung and Quantitive PET Parameters (ID 5338)

      14:30 - 15:45  |  Author(s): Ü. Yılmaz, Ö. Özmen, F. Demirağ, T. İnal Cengiz, P. Akın Kabalak, D. Kızılgöz, İ.O. Alıcı, G. Fındık

      • Abstract

      Background:
      There are differences in terms of survival even in early stage adenocarcinomas and subtypes of tumor are the most particular factor. The aim of the study was to investigate the relationship between International Association for the Study of Lung Cancer (IASLC)/ American Thoracic Society (ATS)/ European Respiratory Society (ERS) grading system of the adenocarcinoma and quantitative PET parameters in terms of survival.

      Methods:
      179 operated adenocarcinoma patients categorized according to grade, histological subtypes (Table 1). All patients underwent complete resection and lymph node resection. Invasive adenocarcinoma (MIA) and adenocarcinoma in situ (AIS) were excluded. PET/CT images were re-evaluated and MTV, TLG and SUV-max of primary tumors were calculated. Correlations between quantitative PET parameters and both tumor and overall survival were analysed.

      Results:
      A strong correlation was detected in terms of tumor size between pathologic tumor size and PET-BT (p<0.001, r=0.816). If the SUV-max of tumor/ lymphadenopathy (LAP) ratio cut-off is taken as <2.5, it is significantly higher to detect metastatic lymph node (p<0.001). SUVmax value had weak negative correlation with survival (p=0.004 r= - 0,220). 49.6 was determined as cut-off value for TLG and 9.68 cm3 was for MTV. 1, 2, 3 and 5 years survival rates were indicated in Table 1 There were significant relation between survival and SUVmax, tumor size (PET-BT and CTT) and TLG (p<0,05). In this study over-all survival rates for 1, 2, 3 and 5 years were 88.9%, 77.8%, 76.4% and 66.1%.

      Survival rates 1 year 2 years 3 years 5 years p value
      TLG<49.6 88.9 70.4 69 51.6 p=0.0051
      TLG>49.6 91.5 87.3 85.9 82.2
      MTV<9.68 89.5 72.1 70.8 53.3 p=0.002
      MTV>9.68 89.6 85.1 83.6 79.9


      Conclusion:
      Although, there was no correlation between tumor grade and PET parameters, PET/CT is an important imaging modality for a more accurate T staging and prediction of lymphatic metastasis and survival. To our opinion quantitative PET parameters can help to decide on treatment options and it is possible to avoid unnecessary treatment and to decrease treatment related morbidity rate.

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      P1.05-079 - Lung Cancer in the Elderly: Factors Affecting Long-Term Survival Following Resection (ID 5802)

      14:30 - 15:45  |  Author(s): P. Balakrishnan, S. Galvin, B. Mahon, J. Riordan, J. McGiven

      • Abstract

      Background:
      Lung Cancer remains the most common cancer in the world . It has progressively become a disease of older people , with the median age at diagnosis now exceeding 65 years . As population grows older demographically , it poses various distinct treatment & management challenges . Thus , we looked into factors associated with long-term survival following pulmonary resections for lung cancer in the elderly patients 70 years or older

      Methods:
      All medical records for these elderly patients with lung cancer who under went pulmonary resections , between years 2000 to 2010 , were reviewed . These data was cross-referenced & checked with the operating theatre ORSOS & national mortality data .

      Results:
      Patients were stratified into various groups . Gender , Median age at diagnosis , patient characteristics , assocciated medical co-morbidities , Pre-operative lung functions tests , extend of pulmonary resections & overall 1 , 2 & 5 years survival was calculated

      Conclusion:
      Stringent & proper selection criterias in elderly patient with lung cancer undergoing pulmonary resections will identify groups of patients that will benefit from these surgeries . Thus , identifying these elderly sub-groups will give new lease of life in survivability following pulmonary resections for lung cancer .

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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 47
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      P1.06-001 - Incidence of Molecular Testing and Outcomes of Treatment with Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer in a Dutch Population (ID 6151)

      14:30 - 15:45  |  Author(s): R. Sluga, F.M.N.H. Schramel

      • Abstract

      Background:
      Introduction: Tyrosine kinase inhibitors (TKIs) for treatment of advanced EGFR mutated adenocarcinoma were shown in many studies to be superior to chemotherapy in terms of progression-free survival. Since most data is derived from studies on Asian populations, there is a lack of data from other ethnicities. In the Netherlands the guidelines recommend that EGFR-mutation analysis should be performed in all patients with stage IIIb and IV adenocarcinoma and a non-small cell lung cancer-not otherwise specified(NSCLC- NOS). The aim of this study was to investigate the compliance to the guidelines in terms of determination of EGFR mutations, prevalence of EGFR mutations and the outcomes of treatment with the TKIs in a cohort of European patients with advanced NSCLC harboring an EGFR mutation.

      Methods:
      Methods: Data was obtained by retrospective analysis of the medical records of patients with a stage IIIb and IV non-small cell lung cancer between 2009 and 2014 in the two top-clinical hospitals in the Netherlands.

      Results:
      Results: The total number of patients included in the study was 1022. Molecular diagnostic tests were performed in 57.8% of patients with advanced adenocarcinoma or NSCLC-NOS. The prevalence of performing molecular diagnostic tests improved significantly between 2009 and 2014 (25,2% to 74,4% respectively). Positive EGFR mutation was found in 43 patients (in 9,1% of all molecular diagnostic tests performed). 72,1% of patients harboring an EGFR mutation were treated with TKIs.A significant overall survival benefit with a mean survival of 763 days was seen in EGFR positive patients treated with TKIs (with or without prior/subsequent chemotherapy) versus 435 days in patients treated with conventional chemotherapy (hazard ratio (HR): 0.719. 95% confidence interval (CI): 0.587-0.881). A large fraction of the patients with EGFR-mutated tumors were either initially or after progression treated with chemotherapy. EGFR positive patients who were prior to TKI treatment treated with chemotherapy had significantly longer survival in comparison to patients treated only with chemotherapy (1201 days vs 435 days respectively (HR: 3.289, 95% CI: 1.551-6.997). 10 patients were not treated with TKIs, either because of poor performance status (40%), patient’s refusal (30%), rapid disease progression (20%) or T790M mutation (10%).

      Conclusion:
      Conclusion: This study showed that incidence of molecular testing improved significantly over the course of the last years, leading to more effective targeted therapy. Overall survival was significantly prolonged in patients harboring an EGFR mutation treated with chemotherapy prior to TKIs, compared to patients without EGFR mutation treated only with conventional chemotherapy

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      P1.06-002 - Contralateral Axillary Lymph Node Metastasis of a Lung Cancer: A Case Report (ID 5382)

      14:30 - 15:45  |  Author(s): O.G. Intepe, M. Yildirim, R. Ustaalioglu, T. Okay

      • Abstract
      • Slides

      Background:
      Primary lung cancer metastasis to axillary lymph node is rare. Routine examination of the axilla is useful way to detect suspicious nodes.

      Methods:
      We evaluated retrospectively medical and pathological records of a male patient at our division who had a primary lung cancer with M1b axillary lymph node metastasis.

      Results:
      A 66-year-old male presented with shortness of breath. His chest x-ray showed a large opacity in the lower one-half of the right lung field. Computed tomography (CT) imaging revealed a solid mass in the right hemithorax measuring 50x50 mm. Positron emission tomography/Computed tomography (PET/CT) demonstrated increased fluorodeoxygucose uptake (Standard uptake value: 9,9) by the mass. Fiberoptic bronchoscopy was performed and transbronchial biopsy was consistent with squamous cell carcinoma. Mediastinoscopy was performed to evaluate the stage of the tumor and biopsies from 2R, 2L, 4R, 4L, 7. mediastinal lymph nodes had negative results. Right lower lobectomy was planned and due to invasion of the right middle lob vein and bronchus, right lower bilobectomy and mediastinal lymph node dissection were performed. Pathological evaluation of the tumor and lymph nodes showed that staging of the tumor was T2b N1 (11. lymph node had metastasis, although 2,4,7,9. lymph nodes were metastasis free). Patient was discharged on post-operative 7. days and received chemotherapy 12 cycles. During follow-up PET/CT revealed increased FDG uptake by mass in the residual right lung(SUV:9.3) and axillary subcentimetric nodule(SUV:11.1). Physical examination of the patient revealed a palpable nodule in the right axilla. Ultrasound guided needle biopsy was performed to this nodule but it had negative result. Before performing pulmonary resection, we decided to dissect this lymph node. 30 months after right lower bilobectomy, axillary lymph node dissection was performed and frozen section procedure demonstrated squamous cell lung carcinoma metastasis to axillary lymph node. Pulmonary resection was cancelled and patient was discharged post operatively 3.day and received chemotherapy again. After 6 month follow-up the patient was dead.

      Conclusion:
      Routine physical examination of axilla is recommended even if mediastinal lymph nodes are metastasis free either at initial presentation or at follow-up of patients. In this case metastatic axillary lymph node was subcentimetric, although according to Austin et al. 14 mm or larger axillary lymph nodes are suggestive of adenopathy. Fishman et al. considered 15mm or larger single axillary lymph node without fatty center as abnormal. Without mediastinal lymph nodes metastasis, contralateral axillary lymph node metastasis could be of systemic origin.

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      P1.06-003 - Anamorelin in Cachectic Patients with Advanced NSCLC, a Post-Hoc Pooled Efficacy Data Analysis of Two Phase 3 Trials (ID 4878)

      14:30 - 15:45  |  Author(s): D. Currow, J. Temel, A. Abernethy, J. Friend, K. Fearon

      • Abstract
      • Slides

      Background:
      Anorexia-cachexia is a multifactorial syndrome frequently experienced by patients with non-small cell lung cancer (NSCLC). It is characterized by decreased body weight (mainly due to muscle loss) and is associated with worsen morbidity, poor tolerance of chemotherapy and reduced survival. The randomized, double-blind ROMANA 1 and ROMANA 2 phase 3 trials in cachectic NSCLC patients, demonstrated that the ghrelin receptor agonist anamorelin was well tolerated, improved body weight, lean body mass (LBM), fat mass (FM) and anorexia/cachexia symptoms and concerns, with no difference in handgrip strength compared to placebo. Here we assessed pooled efficacy and numbers needed to treat (NNT) from ROMANA 1 and ROMANA 2 studies.

      Methods:
      Stage III/IV NSCLC patients with cachexia (≥5% weight loss during prior 6 months or BMI<20 kg/m[2]) were randomized (2:1) to daily oral 100 mg anamorelin or placebo for 12 weeks. Endpoints included changes in LBM, FM, total body mass (TBM) and in self-reported anorexia/cachexia symptoms and concerns. We present the pooled efficacy data from a post-hoc analysis from both trials (anamorelin, N=552; placebo, N=277); treatment differences, 95% CI, NNT and nominal p values from baseline to end of study.

      Results:
      At the end of study, compared with placebo, anamorelin-treated patients significantly increased body composition parameters (LBM, appendicular LBM, FM and TBM), and a greater proportion of patients showed improvements in these parameters (Table). The anamorelin group also significantly improved anorexia/cachexia symptoms and concerns, and compared to placebo, more patients in the anamorelin arm achieved the minimally important difference of 4 points. Figure 1



      Conclusion:
      Anamorelin has anabolic activity while improving symptom burden in cachectic patients with NSCLC. A significantly greater proportion of patients increased lean mass, fat mass and improved anorexia/cachexia symptoms and concern score in the anamorelin arm versus the placebo arm, with favorable NNT.

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      P1.06-004 - Evaluating the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ): Preliminary Results from the Quantitative Pilot Study (ID 5217)

      14:30 - 15:45  |  Author(s): A.M. Liepa, D.M. Bushnell, T.M. Atkinson, K. Debusk, K.P. McCarrier, M.L. Martin, S.J. Coons

      • Abstract
      • Slides

      Background:
      In collaboration with the US Food and Drug Administration (FDA), the Patient-Reported Outcome (PRO) Consortium’s NSCLC Working Group has developed the 7-item NSCLC-SAQ. Content includes cough, pain (2 items), shortness of breath, fatigue (2 items), and appetite. A quantitative pilot study is underway to evaluate the NSCLC-SAQ’s item-level and scale-level performance.

      Methods:
      Eligible subjects with clinically-diagnosed advanced NSCLC from US-based clinical sites completed a questionnaire battery (demographics, NSCLC-SAQ, NCCN/FACT Lung Symptom Index-17 [FLSI-17], Patient Global Impression of Severity [PGIS]) using a tablet computer. For this interim analysis, items were evaluated for response distribution, ceiling/floor effects, missing data, and item-to-item correlations. Exploratory factor and Rasch analyses were examined. Internal consistency reliability was estimated using Cronbach’s coefficient alpha. Construct validity was assessed with Pearson correlations between the NSCLC-SAQ and FLSI-17 Disease-Related Symptom (DRS) subscale. The PGIS was used to assess the NSCLC-SAQ’s known-groups validity.

      Results:
      For this interim analysis, 117 (of the anticipated 150) subjects from nine sites were included. Subjects’ mean age was 64 years old (range 40-85), 55% were female, and 84% were white (non-Hispanic), ECOG performance status at enrollment was: 0 (33%), 1 (50%), and 2 (17%). NSCLC staging was: Stage IIIB (15%) and IV (85%). A total of 34% were treatment-naïve, 32% had received first-line treatment only, and 34% had received second- or third-line treatment. Mean scores for the 7 items of the NSCLC-SAQ ranged from 0.9 to 2.2 using a response scale between 0 (“No at all” or “Never”) to 4 (“Very Severe ” or “Always”). Subjects used the full range of responses (i.e., 0, 1, 2, 3, and 4) and provided answers for all NSCLC-SAQ items. Rasch analyses showed the items were ordered and the person-to-item distribution was acceptable. Factor analysis indicated a single component accounting for 47% of the variance, which supports a unidimensional scale structure and the ability to calculate a total symptom score. Cronbach’s alpha was 0.80. The NSCLC-SAQ total symptom score correlated highly (r=0.87) with the FLSI-17 DRS and was able to discriminate levels of overall symptom severity as assessed by the PGIS (p<0.001).

      Conclusion:
      The NSCLC-SAQ has been developed in accordance with the FDA’s PRO Guidance. This study provides quantitative evidence of adequate item and scale performance. These data will be submitted to the FDA to support qualification of the NSCLC-SAQ as a measure to assess a symptom endpoint for efficacy evaluation and product labeling.

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      P1.06-005 - An International Cohort of Patients with Small Cell Lung Cancer after a Non-Small Cell Lung Carcinoma Oncogene or Non-Oncogene Addicted (ID 4531)

      14:30 - 15:45  |  Author(s): M. Giaj Levra, S. Novello, L. Ferrer, F. Barbieri, J. Mazieres, V. Westeel, N. Girard, M. Poudenx, J. Le Treut, M.R. Migliorino, C. Audigier Valette, A. Madroszyk, C. Leduc, M. Locatelli- Sanchez, A.C. Toffart, D. Moro-Sibilot

      • Abstract
      • Slides

      Background:
      Phenotypic transformation from Non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a resistance mechanism in tyrosine kinase inhibitors (TKIs) treated EGFR mutant tumors. SCLC is also however less frequently diagnosed in patients without EGFR mutations treated with chemotherapy. These transformations are rare and little is known about the clinical and therapeutic characteristics of these patients. In this study we describe and compare the characteristics of SCLC arising from mutant or non mutant NSCLC.

      Methods:
      We performed a multicentric retrospective collection (27 centers in France and Italy) of cases. Between 2005 and 2015, patients with stage III or IV NSCLC with a secondary transformation to SCLC with histological proof were included.

      Results:
      Forty seven cases of SCLC transformation were collected, 34 in EGFR mutant and 13 in non. Most of the patients (n=37, 82%) were stage IV, (n=27, 57%) female and (n=26, 76%) had an exon 19 mutation. The last treatment before transformation was a TKI in 23 (68%) cases in the mutant group and in 3 (23%) patients (erlotinib) in the non-mutant. Median time to SCLC transformation was 17 [IQR, 11-29] months in the mutant group and 26 [IQR 23-36] months in the other (p=0.03). Molecular analyses were not performed in the non mutant group, 25 (74%) had molecular analyses in the EGFR mutant. A driver mutation was identified in 22/25 (88%) patients: in most of the cases the same as the initial, 1 case of ALK fusion and 1 of PI3K mutation. Thirty patients (88%) received at least one line of treatment after transformation in the mutant group, in all cases a platinum-etoposide (P-E) chemotherapy. Median survival from initial diagnosis in the EGFR mutant group was significantly worse 28 [17-41] months vs 49 [36-118] months in the non EGFR mutant group (p=0.01). After transformation, the same tendency was observed with a median survival of 8 [3-12] months for the EGFR mutated patients vs 13 [6-15] months for the non EGFR mutated patients (p=0.06).

      Conclusion:
      SCLC that occurs in EGFR mutant treated by TKIs is more aggressive than classic SCLC, and differs on epidemiological characteristics. These transformed SCLC are not fully explained and we need to define the molecular characteristics of this cohort, before and after transformation and if funded the whole genome sequencing of the tumors to understand this TKIs mechanism of resistant.

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      P1.06-006 - Treatment beyond Progression in Patients with Advanced Squamous NSCLC Participating in the Expanded Access Programme (EAP) (ID 5450)

      14:30 - 15:45  |  Author(s): F. Cappuzzo, A. Delmonte, S. Capici, L. Crinò, A.F. Logroscino, P. Sandri, L. Livi, F. Vitiello, D. Signorelli, L. Calabrò, D. Turci, S. Quadrini, P. Antonelli, S. Giusti, F. Di Costanzo, F. Rastelli, P. Marchetti, G. Finocchiaro, E. Cortesi, A. Ardizzoni

      • Abstract
      • Slides

      Background:
      Response patterns of immunotherapies differ from those seen with other therapies approved for the treatment of tumors. Due to this reason, immunotherapy protocols generally allow patients (pts) to continue treatment beyond investigator-assessed radiographic progressive disease (PD) as long as there is ongoing clinical benefit, but to date no data has been reported regarding treatment beyond PD in routine clinical practice. Here we report the analysis about the subgroup of pts treated beyond initial PD in the italian cohort of nivolumab EAP for pts with squamous non small cell lung cancer (Sq-NSCLC).

      Methods:
      Nivolumab was available upon physician request for pts aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks to a maximum of 24 months. Pts included in the analysis had received ≥ 1 dose of nivolumab and were monitored for adverse events (AE) using Common Terminology Criteria for Adverse Events. Patients were allowed to continue treatment beyond initial PD as long as they met the following criteria: investigator-assessed clinical benefit, absence of rapid PD, tolerance of program drug, stable performance status and no delay of an imminent intervention to prevent serious complications of PD.

      Results:
      With a median follow-up of 5.2 months (range 0-12.9), 363 pts were evaluable for response. Prior to first progression, the objective response rate (ORR) was 14%, with 1 complete response (CR) and 50 (14%) partial responses (PR), and the disease control rate (DCR) was 41%. Sixty-six pts were treated beyond RECIST defined progression, with 23 pts obtaining a non-conventional benefit, meaning a subsequent tumor reduction or stabilization in tumor lesions. In particular, 17 pts obtained a SD and 6 pts obtained a PR. As to July 2016, median overall survival in these pts had not been reached (95% CI: 3.2-4.6) and 6 months and 12 months OS were 75% and 53%, respectively. The safety profile was consistent to what already observed in the general population.

      Conclusion:
      As already observed in clinical trials, these preliminary EAP data seem to confirm that a proportion of pts who continued treatment beyond PD demonstrated sustained reduction or stabilization of tumor burden, with an acceptable safety profile. Further investigations are warranted in order to better define and identify pts who can benefit from treatment beyond progression.

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      P1.06-007 - Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Cancer (NSCLC) (ID 6283)

      14:30 - 15:45  |  Author(s): O. Arrieta, R.L. Luna Palencia, O. Macedo-Pérez, F. Barron, J.F. Corona Cruz, L.A. Chinchilla Trigos, M. Blake Cerda, F. Maldonado Magos

      • Abstract
      • Slides

      Background:
      Cancer represents a large biological spectrum of disease ranging from localized to multisystem involvement with multiple intermediate stages. Oligometastatic NSCLC is thought to carry a better overall survival (OS) but there are few prospective studies that evaluate it.

      Methods:
      Prospective cohort study with NSCLC patients treated at the Instituto Nacional de Cancerologia of Mexico, with stage IV and oligometastatic disease (≤ 5 metastatic lesions). Patients were enrolled to receive, after 4 cycles of systemic treatment with platinum-doublet chemotherapy or 4 months of tyrosine kinase inhibitors in patients with driver mutations, local consolidative treatment for the primary lesion and their metastases with chemoradiotherapy, surgery, radiotherapy, stereotactic radiosurgery or radiofrequency ablation based on the decision of the Multidisciplinary Thoracic Committee of the institution. The primary outcome was overall survival. The study was approved by de Institutional Ethics Committee and registered in clinical trials NCT02805530.

      Results:
      Up to this moment, we have evaluated 29 patients with NSCLC and oligometastatic disease. Of these, 62% males with a median age of 58 years (IQR 52.5-64.5), median CEA 10.2 (IQR 3.25-55), 59% former or currently smokers (median 37.5 package/year), wood-smoke exposure 28%. Overall 90% of the patients presented adenocarcinomas, 28% EGFR mutation (50% deletion of exon 19, 38% mutation on exon 21). At diagnosis 93% of the patients had symptoms mainly cough (48%), dyspnea (30%), neurologic symptoms (26%), weight loss (18%) and dysphonia (15%). We evaluated the oligometastatic disease status with PET-CT and MRI in 66% of the patients and the remaining with CT scan plus MRI. At diagnosis 66% had one or two metastases, 14% three to four metastases and 20% five metastases. For metastatic sites CNS was the main site of metastases in 52% of patients, 28% contralateral lung, 17% bone metastases and 7% at suprarenal. For radical treatment to the primary tumor, 59% chemoradiotherapy, 21% radiotherapy, 28% surgery and 3% radiofrequency. For definite treatment for the metastases, 45% received radiotherapy, 14% chemoradiotherapy and 17% surgery. The mean dose of radiotherapy received for the control of the primary tumor was 56.3 Gy (SD 11.28 Gy) and 29.5 Gy (SD 3.84Gy) for metastases. After multimodal treatment 24% had radiologic complete response. The median OS were 18.26 months (95%CI:10.89-25.64), the median OS for those with and without radiologic complete response were 28.58 months (95%CI:12.98-44.18) and 14.45 months (95%CI:10.40-18.51) respectively.

      Conclusion:
      Patients with oligometastatic NSCLC with agressive treatment have a large OS regardless their mutational status.

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      P1.06-008 - Non-Small Cell Lung Cancer in Octogenarians: Real-Life Clinical Practice; Characteristics, Therapy and Survival (ID 4034)

      14:30 - 15:45  |  Author(s): H. Koyi, G.N. Hillerdal, K.G. Kölbeck, D. Brodin, E. Brandén

      • Abstract

      Background:
      Globally, more people are surviving to older age; consequently, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice.

      Methods:
      A retrospective observational study of all elderly (>80 years) patients with NSCLC referred to Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010 and followed until June, 2016.

      Results:
      During the period 2662 patients were newly diagnosed with lung cancer. 485 (12.2%) were 80 years or older. 33 (6.8%) hade small cell lung cancer and were excluded, leaving 452 for the study. 216 (47.8%) were male. Mean, median, and range age for males were 83.8, 83, and 80-96 years, respectively. These figures for females were 83.7, 83, and 86-95. 28 (6.2%) of the population were 90 years old or older. 77.8% patients were current or former smokers with significant differences between the genders (p<0.001). There was no difference in performance status (PS) between the genders (p<0.93), with PS 0-1 in 45%, PS2 in 26% and PS3-4 in 29%. 33.9% of patients were diagnosed in stages 1-II, 34.1% in stage III and 31.9% in stage IV. Most of the patients, 45.6%, had adenocarcinoma, 18.1% squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. There were significant differences in treatment modalities (p=0.040). Chemotherapy was given in 9.5%, local radiotherapy in 17%, stereotactic body radiotherapy (SBRT) in 10.6%, 6.9% underwent surgery and 209 (46.2%) were not given any therapy. Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth line. Median overall survival was 115 days in patients given no therapy and 362 days in patients given any therapy. Patients who underwent surgery had a median overall survival of 5,6 years compared to 3,5 years for patients given SBRT (p=0.0187). There were no significant differences in survival between genders.

      Conclusion:
      Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.

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      P1.06-009 - Determining Optimal Array Layouts for Delivering TTFields to the Lungs Using Computer Simulations (ID 4530)

      14:30 - 15:45  |  Author(s): N. Urman, Z. Bomzon, U. Weinberg, H.S. Hershkovich, E. Kirson, Y. Palti

      • Abstract
      • Slides

      Background:
      Tumor Treating Fields (TTFields) are low intensity, alternating electric fields in the intermediate frequency range. TTFields disrupt mitosis by interfering with formation of the mitotic spindle. The therapy is FDA approved for the treatment of glioblastoma (GB). A study to assess the efficacy of TTFields in combination with chemotherapy for the treatment of mesothelioma is underway, and a pivotal study testing the efficacy of TTFields in NSCLC is planned. TTFields are delivered through two pairs of transducer arrays applied to the patient's skin. In-vivo and In-vitro studies suggest that treatment efficacy increases with field intensity. Therefore personalizing the array placement to deliver optimal field distributions is important and is a prerequisite when treating GB patients. However, optimal array layouts for lung cancer patients have not yet been determined. Here we present a finite element simulations-based study investigating optimal array layouts in male and female anatomic models.

      Methods:
      The study was performed using the Sim4Life software package and the DUKE and ELLA computational models (ZMT, Zurich, Switzerland). To represent individuals with a variety of body dimensions, the models were linearly scaled. The distribution of TTFields within the thorax of these models was calculated for a set of array layouts. The layouts were ranked with highest scores for those that conformed well to body contours and delivered uniform high intensity fields to the lungs.

      Results:
      Uniform field distributions within the lungs are obtained when the arrays are axially-aligned with the parenchyma as much as anatomically possible. Generally, the layouts that received the highest scores were those in which one pair of arrays delivered an electric field from the anterolateral to the posterior-contralateral aspect of the patient, with the second pair inducing the field from the antero-contralateral to the posterolateral aspect of the patient. However, due to body contours, this type of layout does not adhere well to smaller females, potentially hampering the efficient delivery of TTFields. Therefore, for smaller females, a layout in which one pair of arrays is placed on the lateral and contralateral aspects of the patients, and a second set of arrays is placed on the anterior and posterior aspects of the patient is preferred.

      Conclusion:
      This study provides important insights into how TTFields distribution in the lungs is influenced by the array layout. These results should be accounted for when developing guidelines for transducer array placement on the thorax.

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      P1.06-010 - Analysis of the Incidence of Cancer Cachexia in Patients with Advanced Lung Cancer at Referral to a Dietitian (ID 4871)

      14:30 - 15:45  |  Author(s): A. Hug, I. Phillips, L. Allan, J. Mendis, V. Ezhil

      • Abstract

      Background:
      Lung cancer is the second most common cancer diagnosed in men and women in the UK with a very poor 5 year survival (10%). There is a lack of robust data on the stage of cachexia in which patients with lung cancer present. The severity of cachexia can influence overall outcomes and a patient’s quality of life. Refractory (irreversible) cachexia indicates a poor prognosis.

      Methods:
      We reviewed all patients diagnosed with metastatic primary lung cancer that were referred to the Macmillan Oncology Dietitians over a 4 year period at the Royal Surrey County Hospital. Reasons for referral commonly included: weight loss, glycaemic control in diabetes, decreased oral intake and food texture modification. We compared self-reported usual body weight (UBW) to weight at referral. Patients were defined as cachectic if weight loss was >5% and refractory cachexia if survival was <90 days from dietitian review.

      Results:
      Figure 1 310 patients with incurable lung cancer were reviewed by the dietitian. Mean age was 68.8 (range 36-89). 42% were female, 58% were male. Mean weight loss was 10%. 76% of patients had lost >5% of usual body weight. Mean pre-cancer body mass index (BMI) was 26.9 (kg/m2), mean BMI at referral was 23.0 (kg/m2). Median survival of non-cachectic and cachectic cohorts were different (299 vs 188 days respectively, p=0.0078). 24% (73 patients) had refractory cachexia.



      Conclusion:
      Our study shows cachexia is very common (76%) in lung cancer and affects survival. A quarter of patients had refractory cachexia. BMI is an insensitive measure of weight loss. Early symptom control improves survival in lung cancer and this data suggests patients are routinely being referred too late to a dietitian. Cachexia in lung cancer is a significant clinical problem. Could upfront assessment of cachexia improve outcome in patients with advanced lung cancer? We propose to investigate this further.

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      P1.06-011 - Altered Body Composition and Fat Loss in Advanced Non-Small Cell Lung Cancer (ID 4212)

      14:30 - 15:45  |  Author(s): A. Mohan, R. Poulose, A.A. Ansari, R. Guleria, K. Madan, V. Hadda, G.C. Khilnani

      • Abstract

      Background:
      Assessment of body composition, including fat mass and fat%, is a useful measure of nutritional status in cancer and may help guide nutritional interventions. However, these abnormalities have not been well documented in lung cancer. We aimed to study alterations in parameters of body composition in Non small cell lung cancer (NSCLC).

      Methods:
      A retrospective chart review was conducted of all newly diagnosed patients with NSCLC. Age and sex matched healthy controls were recruited prospectively. Disease staging was done according to the American Joint Committee on Cancer (7th edition). Performance status was asssessed using the Karnofsky performance Scale(KPS), and the Eastern Cooperative Oncology Group (ECOG). Details of body composition including basal Metabolic Rate (BMR), total body water (TBW), fat mass, and Fat-free mass (FFM) were calculated by bioelectric impedance method using TANITA TBF 300 body composition analyzer.

      Results:
      A total of 256 patients (83.6% males) and 211 controls (81.5% males) were studied. The mean (SD) age of patients was 54.5(9.0) years, median smoking index was 598 (range, 0-2500) and mean duration of symptoms was 158.3(91.7) days. Median KPS was 80 (range, 40-100). Majority had Stage IV disease (54.7%), followed by Stage III (41.4%) and Stage II (3.9%). All measured components of body composition were significantly lower in NSCLC compared to controls (Table).Among patients with normal body weight (BMI 18.5 – 25 kg/m[2]), the TBW and FFM were significantly lower compared to their healthy counterparts. Figure 1



      Conclusion:
      NSCLC is associated with significant malnutrition and altered body composition, especially reduction in the percentage of body fat. Nutritional interventions must, therefore, be tailored accordingly for these patients.

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      P1.06-012 - Central and Peripheral Lung Adenocarcinomas Exhibit Different Timing and Predilection for Distant Metastasis (ID 5649)

      14:30 - 15:45  |  Author(s): T. Klikovits, Z. Lohinai, K. Fabian, M. Gyulai, A. Fodor, J. Varga, E. Baranya, O. Pipek, I. Csabai, Z. Szallasi, J. Tímár, B. Hegedus, B. Dome, J. Moldvay

      • Abstract

      Background:
      Although distant metastases are major factors for unfavorable prognosis in lung adenocarcinoma (ADC), metastatic patterns have not been widely analyzed in this malignancy.

      Methods:
      Clinicopathological data of 1126 ADC patients (541 men, 585 women, mean age: 62.1 ± 9.4 years, 32-88 years) were studied retrospectively, focusing on the localization of primary tumor and distant metastases. Metastases diagnosed at the time of primary tumor diagnosis were defined as early metastases. For statistical analyses, Fisher's exact test and a chi-squared independence test were performed.

      Results:
      At time of diagnosis, 621 patients had stage IV disease. 435 of them had a solitary organ metastasis, mainly in the contralateral lung (n=187), in the brain (n=66), or in the bone (n=59). During the follow up period another 242 patients developed distant metastasis. 39% of all patients had central (i.e. endobronchially visible) tumor. In cases with early-, late-, and non-metastatic disease, the proportions of central tumors were 43%, 35% and 31%, respectively. Central primary tumors were significantly more likely to give rise to early metastases than peripheral ones (p=0.021). When comparing central and peripheral lung cancers according to their metastatic sites, in central tumors lung metastases appeared significantly earlier (p=0.017), while in peripheral ones bone metastases appeared significantly later (p=0.015). There were significant differences in the metastatic organ distributions of central vs. peripheral primary tumors for early (p=0.025) and late (p=0.009) metastases. There was no significant difference in the metastatic organ distributions of right vs. left lung primaries both for early and late metastases. In right lung tumors brain metastases appeared later (p=0.047). No significant difference was observed in the metastatic organ distributions of primary tumors of the upper vs. lower lobes for early (p=0.051), and late (p=0.528) metastases. Early appearance was characteristic for lung, pleural, and adrenal involvement (p<0.001 in all comparisons), while late development was typical for brain metastasis (p=0.002). Bone, liver, subcutaneous, and pericardial metastases showed no such tendencies.

      Conclusion:
      There are significant differences in metastatic organ distributions of central vs. peripheral lung cancers both for early and late metastases. Central primary tumors are more likely to give rise to early metastases than peripheral ones. Results of molecular subgroup analyses will be presented during the Conference.

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      P1.06-013 - Patient Characteristics and Survival: A Real-World Analysis of US Veterans With Stage IV Adenocarcinoma vs Squamous NSCLC (ID 4737)

      14:30 - 15:45  |  Author(s): M.I. Patel, M. Parisi, M. Patel, C. Pelletier, C.L. Bennett, P. Georgantopoulos

      • Abstract

      Background:
      5-year survival rate in patients with stage IV NSCLC was 1%. Stage IV adenocarcinoma (ADENO) and squamous (SCC) account for 44% and 18% of stage IV NSCLC diagnoses, respectively. Patient characteristics and survival in US veterans with stage IV ADENO vs SCC NSCLC were examined.

      Methods:
      Patients with a unique diagnosis of stage IV NSCLC between 1/1/2010 and 12/31/2015 from the US Veterans Affairs (VA) health system database were included. Lung cancer diagnoses were confirmed by VA Central Cancer Registry and Veterans Health Administration National Patient Care Database. Patients were excluded if they did not have 1 VA visit within 1 year before diagnosis.

      Results:
      13,956 patients with stage IV NSCLC were included (ADENO: n=6525 [47%]; SCC: n=3421 [25%]). Baseline characteristics were similar for ADENO vs SCC, including age at diagnosis (mean, 68.8 vs 69.2 y), married at diagnosis (43.9% vs 42.2%), had known Agent Orange exposure (17.4% vs 16.3%), and the majority were white (60.8% vs 63.8%). For ADENO vs SCC, more patients were former smokers (39.5% vs 34.3%), but fewer were current smokers (53.9% vs 61.1%). For ADENO vs SCC, occurrence of brain or bone metastases were higher and incidence of chronic obstructive pulmonary disease or chronic pulmonary disease were lower (Table); age at death (mean, 69.3 vs 69.7 y) and time from diagnosis to death (TDD; mean, 0.56 vs 0.55 y) were similar. More ADENO vs SCC patients received chemotherapy (48.5% vs 44.1%). Mean TDD was longer in patients treated with chemotherapy vs not (ADENO: 0.86 vs 0.31 y; SCC: 0.84 vs 0.35 y).Figure 1



      Conclusion:
      ADENO was more prevalent than SCC in veterans with stage IV NSCLC, similar to the overall population; stage IV SCC prevalence was higher in the veterans than in the overall population. Mean TDD was longer in chemotherapy-treated patients regardless of histology.

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      P1.06-014 - What Factors Determine Treatment Satisfaction in Patients with Advanced NSCLC Receiving Chemotherapy? (ID 6025)

      14:30 - 15:45  |  Author(s): S. Visser, M. De Mol, N. Van Walree, J. Van Toor, B. Den Oudsten, B. Stricker, J.G. Aerts

      • Abstract
      • Slides

      Background:
      In advanced non-small cell lung cancer (NSCLC) treatment decisions regarding palliative chemotherapy are complex due to limited survival gain and treatment-related toxicities. Insight into determinants of patients’ treatment satisfaction may impact decision-making and patient care. We determined the relation of patient- and treatment-related variables to treatment satisfaction.

      Methods:
      In a prospective observational multi-center study, patients with stage IIIB or IV NSCLC receiving pemetrexed (PEM)-based chemotherapy as first- or second-line treatment were enrolled. After four cycles of chemotherapy, patients completed the WHO Quality of Life-BREF (WHOQoL-BREF), which contains one item measuring overall QoL on a 1-5 scale, and the Cancer Therapy Satisfaction Questionnaire (CTSQ). The CTSQ was recently validated (Cheung et al, Qual Life Res. 2016;25(1):71-80). It consists of 16 items scored on a 1-5 scale and contains three domains. Only satisfaction with therapy (SWT) and feelings about side effects (FSE) were used. The domain scores range between 0-100, with higher scores representing better SWT and more positive FSE. We collected sociodemographic information and ECOG performance status at baseline. Adverse events (cancer- or therapy-related) during treatment were weekly registered (CTCAE 3.0). Tumor response measurements were obtained (RECIST 1.1). Patient- and treatment-related determinants univariably associated with SWT (p<0.05) were analyzed using multivariable linear regression (method: Enter).

      Results:
      Of the 95 patients receiving four cycles of chemotherapy, 69 patients completed the CTSQ. The majority of these patients had stage IV NSCLC (87.7%) and received PEM-based therapy as first-line treatment (92.3%). Treatment resulted in stable disease (SD; 53.8%), partial response (PR; 40.0%) and progressive disease (PD; 6.2%). The mean SWT domain score was 79.6±13.1. Univariably, higher patients’ age (p=0.034), tumor response (PR vs. SD or PD, p=0.040), overall QoL (p=0.008) and FSE (p=0.004) were significantly related to SWT. The frequency of (severe) adverse events was not associated with SWT (p=0.546). After including these variables in the multivariable analysis, only age (β=0.44; 95%CI (0.09-0.79)) and FSE (β=0.13; 95%CI (0.00-0.26) were independently related to SWT.

      Conclusion:
      Importantly, higher SWT in elderly supports the opinion that palliative chemotherapy should not be reserved for younger age groups. Although symptomatic adverse events are known key contributors to QoL, the frequency of (severe) adverse events was not related with SWT. However, in patients with better FSE treatment satisfaction was higher. Therefore, patients’ education about and management of adverse events may have added value in maintaining patients’ well-being during chemotherapy, ultimately resulting in higher treatment satisfaction. This study is funded by ZonMw, the Netherlands.

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      P1.06-015 - Designing Transducer Arrays for the Delivery of TTFields Whilst Maximizing Patient Comfort and Field Intensity in the Thorax (ID 4897)

      14:30 - 15:45  |  Author(s): Z. Bomzon, H.S. Hershkovich, U. Weinberg, E. Kirson, S. Strauss

      • Abstract
      • Slides

      Background:
      Tumor Treating Fields (TTFields) are an anti-mitotic therapy that utilizes low intensity electric fields in the intermediate frequency range to disrupt cell division. A study to test the efficacy of TTFields in combination with chemotherapy for the treatment of mesothelioma is underway, and a pivotal study testing the efficacy of TTFields in treating NSCLC is planned. TTFields are delivered via two pairs of transducer arrays placed on the patient's skin. The transducer arrays comprise a set of ceramic disks that make electric contact with the skin through a thin layer of conductive medical gel. The disks in the arrays currently in use are arranged in an almost rectangular pattern. One pair of arrays is placed on the posterior and anterior sides of the patient’s thorax. The other pair is placed on the lateral and contralateral aspects of the patient. This configuration has several limitations: The array placed on the chest may not adhere well to body curvature, leading to sub-optimal electric contact that reduces field intensity in the tumor. In females and obese individuals, fields generated by arrays placed on the anterior and posterior have to traverse thick layers of adipose in the breast. The high resistivity of these layers damps the intensity of TTFields in the lungs. Here we present novel array designs intended to overcome these limitations.

      Methods:
      Multiple concepts for arrays designed to adhere comfortably to the body, whilst avoiding regions of high adipose were proposed. Finite element simulations using realistic computational phantoms were used to evaluate the field distribution generated by these arrays, and optimize their design.

      Results:
      Novel array designs for delivering TTFields to the lungs were developed. These arrays are not designed as large patches, but comprise sets of interconnected small patches that adhere to the natural contours of the patient's bodies. Simulations showed that these arrays deliver uniform field distributions to the lungs. A particularly noteworthy design is a pair of arrays in which one array was shaped as a circular ring placed around the neck and shoulders, and the second array was shaped as a belt placed on the lower torso. This design yielded a highly uniform and intense field directed longitudinally throughout the torso.

      Conclusion:
      The arrays presented in this study deliver high field intensities to the thorax whilst maintaining patient comfort. These designs could help to improve the outcome of TTFields therapy.

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      P1.06-016 - Pulmonary Tuberculosis among Newly Diagnosed-Therapy Naive Advanced NSCLC  in Persahabatan Hospital Jakarta Indonesia (ID 5886)

      14:30 - 15:45  |  Author(s): J. Zaini, S.L. Andarini, R.R. Ramadhani, E. Syahruddin, A. Hudoyo

      • Abstract

      Background:
      The prevalence of lung cancer increased in the recent years in Indonesia, meanwhile pulmonary tuberculosis (TB) is still a major public health problems in this community. Malignancy such as lung cancer increase the risk of tuberculosis infection and reactivation, therefore evaluation of tuberculosis among lung cancer patients is needed

      Methods:
      Newly diagnosed, therapy-naive advanced NSCLC subjects were enrolled from a referral respiratory hospital Persahabatan Hospital Jakarta Indonesia between 2014-2015. Active pulmonary tuberculosis were diagnosed by Xpert MTB/ RIF from induced sputum and LPA M. TB culture. Latent Tuberculosis Infection (LTBI) was determined by Quantiferon-TB Gold-In-Tube (QFT-GIT). Demographic and clinical characteristics were evaluated.

      Results:
      Of 50 lung cancer subjects enrolled, 30 (60%) men with mean of age 55 years old (31- 74 years old). Eighty five percents were adenocarcinoma (42 subjects) and 15% squamous cell lung cancer. Most of them were at end stage (87% stage IV and 13%stage IIIB) with WHO performance status (PS) 1 to 3 (20 % PS 1, 70% PS 2 and 10% PS 3). Comorbidities among this group were COPD (3 ssubjects), diabetes mellitus (2 subjects), hypertension (4 subjects), congestive heart failure (1 subjects). Active tuberculosis were diagnosed in 2 % (1 subject). Based on Quantiferon results, 14 % were positive (7 subjects) and classified as latent tuberculosis infection (LTBI); 60% (30 subjets) classified as non-LTBI (negative Quantiferon result) but 12 (24%) indeterminate cases. The characteristics of LTBI patients were 67% men, two third were adenocarcinomas, 80% stage IV of lung cancer, 80% having WHO PS 2 and 3, 50% were underweight (body mass index (BMI) < 17.5.

      Conclusion:
      Active pulmonary tuberculosis and latent tuberculosis infection is common among newly diagnosed therapy naive advanced NSCLC in this population. Most of them are men, adenocarcinoma, PS 2-3, and half of them were underweight.

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      P1.06-017 - Observational Study on Prolonged Disease Stabilization in Advanced NSCLC EGFR WT/Unknown Patients Treated with Erlotinib in Second Line (ID 4998)

      14:30 - 15:45  |  Author(s): F. Grossi, A. Montanino, M.R. Migliorino, A. Santo, M. De Tursi, A. Delmonte, F. Vitiello, M. Mencoboni, V. D'Alessandro, G. Romano, E. Rijavec, A. Misino, A. Chella, M. Roselli, S. Cavuto

      • Abstract
      • Slides

      Background:
      In advanced NSCLC, erlotinib treatment was shown to improve survival independently of EGFR status and induce high rates of prolonged stable disease (SD). It has previously been reported that, after second-/third-line erlotinib, PFS and OS are long-lasting and similar between patients with SD ≥8 months and those attaining partial/complete response (PR/CR). The present study investigated the clinical value of SD in a real-world setting of advanced NSCLC.

      Methods:
      This Italian multicenter observational study enrolled patients with stage IIIB-IV NSCLC on second-line erlotinib and wild-type/unknown EGFR mutational status, with SD, CR or PR per RECIST v1.1 lasting for ≥4 weeks. Patients were observed from the beginning of erlotinib for approximately 8 months or until death. Primary end-points were the rate and duration of SD (i.e. time interval from erlotinib start to the last evidence of SD by RECIST) or CR+PR. Secondary end-points were OS and PFS (i.e. time interval from the erlotininb start to the first evidence of progression), estimated by the Kaplan-Meier method and calculated by response duration or disease stabilization. Adverse events occurring during the observation period were also recorded.

      Results:
      At the cut-off date of 30/04/16, 144/172 (83.7%) enrolled patients were evaluable for response (mean age 69.1 years, 61.8% males). At the start of erlotinib treatment, 85.4% were non-smokers, 89.6% had an ECOG-PS of 0-1, and 84.7% had stage IV NSCLC (83.3% adenocarcinoma and 11.8% squamous cell carcinoma). Following second-line erlotinib, 82.6% (119/144) of patients achieved SD and 17.4% (25/144) PR. Notably, SD was maintained for ≥8 months in 27% (39/144) of cases. At the end of the observation period, 12 (8.3%) patients had deceased, none with SD ≥8 months. Median OS had not been reached by the entire population. According to SD duration, median OS was 4.3 months if <2 months, 6.8 if between 2 and 5 months, and not reached if ≥5 months or if PR. Median PFS was 9.0 months in the entire population, 8.7 among patients with SD and 10.8 with PR. According to SD duration, PFS was 1.4 if <2 months, 4.4 months if between 2 and 5 months, 7.5 if between 5 and 8 months and 10.5 if ≥8 months. No unexpected toxicities were observed.

      Conclusion:
      In advanced NSCLC, second-line erlotinib yielded a high rate of SD, lasting ≥8 months in 27% of cases, with PFS similar to PR patients and low mortality rate.

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      P1.06-018 - Treatment Patterns and Clinical Practices of Advanced (Stage IV) Non-Small Cell Lung Cancer (NSCLC) in Europe - A Structured Literature Review (ID 4369)

      14:30 - 15:45  |  Author(s): T. Brodowicz, D. Niepel, E. Booth, R.K. Hernandez, G. Braileanu, M. Cawkwell, J. Amelio

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) is associated with high mortality and a poor five-year survival. Novel therapies in the pipeline hold promise to address these unmet needs and improve prognosis. Furthermore, their introduction is expected to bring considerable changes to the European treatment landscape. The aim of this review is to provide an overview of the current treatment patterns for advanced (stage IV) NSCLC across five European countries (EU5; France, Germany, Italy, Spain and the UK).

      Methods:
      A structured literature search was conducted in electronic databases for studies published between January 2010 and February 2016 to identify publications reporting on treatments for stage IV NSCLC in European populations. Additional literature searches of relevant European conferences and internet-based sources were performed to ensure the most up-to-date evidence and published clinical guidelines in the EU5 countries were captured.

      Results:
      A total of nine relevant articles (five full-text studies and four conference abstracts) as well as ten clinical guidelines were eligible for inclusion in the literature review. All publications identified were observational studies of advanced NSCLC treatment patterns in the EU5 with data collected between 2005 and 2014. The most commonly reported first-line treatments were cisplatin, carboplatin and pemetrexed, a trend supported by data from individual countries where platinum-based regimens were the most widely prescribed. Other systemic treatments received included non-platinum based regimens, bevacizumab and investigational drugs. The most common second- and third-line treatment options were docetaxel, erlotinib and gemcitabine. There was limited published literature on lines of treatment prescribed in the UK whereby only information on second-line prescribed therapies was available. These included docetaxel, erlotinib, and pemetrexed. Based on this data, treatment patterns appear to be in-line with recommendations from European and national guidelines of NSCLC treatments with the exception of crizotinib and afatinib, which were not approved at the time of the data collection for the majority of studies included in the literature review.

      Conclusion:
      Treatment practices in advanced NSCLC are similar across EU5 countries with slight variations depending on the time period assessed and most notably on the approval and availability of novel therapies. Overall, treatments reported as part of clinical practices across EU5 countries prior to 2010 are still recommended by both national and European-wide guidelines. Furthermore, there is a paucity of comprehensive treatment patterns information for the UK.

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      P1.06-019 - The Possibility of the Additional Local Therapy to Systemic Chemotherapy in Advanced Lung Cancer Cases with Multiple Metastases (ID 4488)

      14:30 - 15:45  |  Author(s): T. Honda, H. Uehara, M. Natsume, Y. Fukasawa, T. Sakamoto, R. Usui, S. Ota, Y. Ichikawa, K. Watanabe, N. Seki

      • Abstract

      Background:
      In stage IV non-small cell lung cancer (NSCLC) patients with multiple metastases, a various pattern of disease progression is observed, including the growth of only primary site, the growth of only pre-existing metastatic site, or the appearance of new metastatic site. The aim of our study is to evaluate the detailed recurrence pattern in patients with stage IV NSCLC, and is also to evaluate whether a specific patient’s population exists whose disease progression is well controlled by the additional local therapy, such as surgery or radiotherapy to the primary or pre-existing metastatic site, during or after the systemic chemotherapy.

      Methods:
      NSCLC patients in stage IV admitted to our hospital from 2012 to 2014 were examined retrospectively. The recurrence pattern was classified into the following groups; the growth of primary site, the growth of pre-existing metastatic site, or the appearance of new metastatic site. Furthermore, progression-free survival (PFS), overall survival (OS), and new lesion-free survival (NFS) of these groups were examined, respectively.

      Results:
      Patients treated with chemotherapy for stage IV NSCLC were 114 cases. The median age was 70 years old, and male was 74 cases. The number of platinum-based combination regimen was 71 cases, monotherapy was 16 cases, epidermal growth factor receptor tyrosine kinase inhibitor was 25 cases, crizotinib was two cases. In the first-line chemotherapy, median PFS, median OS and median NFS in all patients were 172 days, 417 days and 270 days. Median PFS, median OS and median NFS in patients for the growth of primary site were 235 days, not reached and not reached. Median PFS, median OS and median NFS in patients for the growth of pre-existing metastatic site were 171 days, 250 days and 205 days. Median PFS, median OS and median NFS in patients for the appearance of new metastatic site were 149 days, 423 days and 149 days.

      Conclusion:
      The prognosis of the appearance of new metastatic site group seems to be worse than the growth of primary site group in the pattern of disease progression in the first-line chemotherapy. And the prognosis of the growth of pre-existing metastatic site group seems to be worse than the appearance of new metastatic site group. In the stage IV NSCLC therapy, there is a possibility that the treatment outcomes will be improved according to well controlled the pre-existing metastatic site by the additional local therapy.

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      P1.06-020 - Prevalence of Autoimmune Disease in US Veterans With Non-Small Cell Lung Cancer (NSCLC) (ID 4745)

      14:30 - 15:45  |  Author(s): M.I. Patel, M. Parisi, C. Pelletier, C.L. Bennett, P. Georgantopoulos

      • Abstract

      Background:
      Immunotherapy has emerged as an effective treatment strategy in cancer; patients with preexisting autoimmune diseases are often restricted from use. The prevalence of autoimmune disease was 12.5% worldwide (Lerner, Int J of Celiac Disease, 2015) and 24.6% in US patients with lung cancer (LC) (Khan, JAMA Oncol 2016). We report autoimmune disease prevalence in veterans with NSCLC in a real-world setting.

      Methods:
      Patients with a unique diagnosis of NSCLC between 1/1/2010 and 12/31/2015 were included. Diagnoses were confirmed by VA Central Cancer Registry and Veterans Health Administration National Patient Care Database. Patients were excluded if they had <1 VA visit within 1 year prior to diagnosis. Baseline autoimmune diseases were identified using ICD-9 codes for 36 organ-specific and 7 systemic autoimmune diseases. Autoimmune disease was defined as having ≥1 claim of any type (broad definition) or having ≥1 inpatient claim or ≥2 outpatient claims ≥30 days apart (narrow definition).

      Results:
      40,371 patients with NSCLC were included (stage IV adenocarcinoma n=6525, stage IV squamous cell carcinoma (SCC) n=3421). Almost all patients were male (99.9%). Autoimmune disease prevalence was greater per broad vs narrow definition in all patients (15.7% vs 13.6%), adenocarcinoma patients (13.4% vs 11.0%), and SCC patients (15.0% vs 12.3%). By broad definition, 13.4% of all patients, 11.7% of patients with stage IV adenocarcinoma, and 13.0% of patients with stage IV SCC had 1 autoimmune disease; 2.3%, 1.7% and 2.0% had >1 autoimmune disease, respectively. The most common autoimmune diseases in all 3 patient populations were psoriasis, chronic rheumatic heart disease (CRHD), rheumatoid arthritis (RA), Addison disease, and ulcerative colitis (Table).Figure 1



      Conclusion:
      Prevalence of autoimmune disease was lower in the predominantly male US veterans with NSCLC than the general population with LC; the prevalence was similar regardless of stage or histology. The most frequent autoimmune diseases were psoriasis, CRHD, and RA.

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      P1.06-021 - Treatment Patterns and Healthcare Resource Use from a Retrospective Cohort of Japanese Patients with Advanced Non-Small Cell Lung Cancer (ID 4632)

      14:30 - 15:45  |  Author(s): T. Kato, K. Mori, K. Minato, H. Katsura, K. Taniguchi, A. Arunachalam, S. Kothari, X. Cao, H. Isobe

      • Abstract
      • Slides

      Background:
      The treatment landscape for advanced/metastatic non-small cell lung cancer (NSCLC) has changed with the advent of targeted therapies and the use of companion diagnostics.

      Methods:
      The primary objective of this multi-site, retrospective, chart review study was to describe the treatment patterns, Biomarker (Bmx) testing practices and health care resource use (HCRU) in patients who initiated first line therapy (1LT) for newly diagnosed Stage IIIB/IV NSCLC between January 2011 - July 2013 in Japan. Data were analyzed descriptively. Overall survival (OS) was estimated using the Kaplan-Meier method.

      Results:
      Of the 175 Japanese patients 70% were male, 19% non- smokers, mean age of 68.8 years (SD=7.75), 83% stage IV and 74 % (n=129) with non-squamous (NSq) histology. 60% (n=105) received second line therapy (2LT) and 31% (n=55) received third line + therapy (3L+T). 85% (n=110) of the NSq and 40% (n=17) of the squamous (Sq) patients received at least one Bmx test. 81% (n=105) and 19% (n=25) of NSq patients, and 40% (n=17) and 24% (n=4) of Sq patients received an EGFR and ALK test, respectively. EGFR Tyrokinase Inhibitors were most commonly used among NSq EGFR mutated patients (n=44) across all lines. 86% (n=38) of the patients used Gefitinib in 1LT and Erlotinib was used in 2LT (n=11 of 30, 37%) and 3LT (n=9 of 15, 60%) patients. All ALK positive patients (n=2) in 1L received anti-ALK therapy (Crizotinib). Among NSq EGFR/ALK negative or unknown patients (n=83), 89% (n=74) received platinum combinations, most commonly carboplatin+paclitaxel (n=22, 26.5%). Single agents (n=29, 67% and n=11, 50%) were commonly used in NSq EGFR/ALK negative or unknown patients receiving 2LT (n=43) and 3LT (n=22); most commonly docetaxel (n=15, 35% & n=5, 23%). Majority of the 1LT patients with Sq histology (36/43, 84%) received platinum combinations therapy; most commonly carboplatin+paclitaxel (51%). Among 2LT, 67 % (n=20) received a single agent, most commonly docetaxel (n=14, 47%). Single agents were commonly used in 73% (n=11) of the patients receiving 3L+T. Overall, the average length of stay, regardless of line of therapy, was 24.6 days per admission. Duration of treatment was longest for 1LT (mean [SD] 140 [175] days), followed by 2LT (66 [129] days) and 3L+T (65 [83] days).Median OS for Japan from start of 1LT & 2LT was 9.9 and 4.7 months, respectively.

      Conclusion:
      NSq patients are frequently tested for Bmx in Japan. Treatment is personalized according to mutation status and is in concordance with recommended guidelines.

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      P1.06-022 - Clinical Characteristics of Survival Outliers in Stage IV Adenocarcinoma Lung Cancer Patients (ID 4304)

      14:30 - 15:45  |  Author(s): A. Fung, A. D'Silva, H. Li, S. Otsuka, D..G. Bebb

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer deaths among men and women in Canada. Many lung cancer patients are diagnosed at advanced stages of disease, which is associated with poor survival outcomes. The mean survival of stage IV non-small cell lung cancer (NSCLC) patients is typically less than 12 months; however, there appears to be a small subset of patients with advanced disease that live substantially longer than the norm. Our study aims to determine whether certain clinical characteristics correlate with longer survival in stage IV NSCLC patients.

      Methods:
      Data on 1803 stage IV NSCLC patients (1291 adenocarcinoma, 512 squamous cell carcinoma) from 1999-2011 were extracted from the Glans Look Lung Cancer database. Adenocarcinoma data is presented here; squamous cell carcinoma data analysis is ongoing. Clinical characteristics such as age, gender, ethnicity, smoking history, histology, molecular testing, metastatic disease, treatments, and socioeconomic factors were compared between survival outliers and patients with average survival. Survival outliers were defined as those patients who lived > 5 years, or greater than 2 standard deviations from mean survival (42.1 months).

      Results:
      In the survival outlier group, there were 25 patients who lived >5 years, and 59 who lived >42.1 months. Survival outliers included a higher percentage of females, had a smaller smoking history, smaller tumour size at diagnosis, received more treatment lines, and had lower metastatic disease burden at diagnosis (P<0.05 in the outlier group with survival >42.1 months). Upon further characterization of metastatic disease, there appears to be survival outliers associated with no liver metastases and less sites of metastases at diagnosis, as well as with stage M1a disease compared to stage M1b.

      Conclusion:
      Adenocarcinoma patients with localized and lower metastatic disease burden and no liver metastases at the time of diagnosis appeared to live longer than their counterparts. Further statistical analysis is ongoing to determine the significance of other clinical characteristics with respect to survival. The present study will help us better understand the importance of various clinical parameters and their association with survival, in hopes of improving outcomes for lung cancer patients in the future.

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      P1.06-023 - Clinicopathological Characteristics of Axillary Lymph Node Metastasis in Lung Cancer (ID 3757)

      14:30 - 15:45  |  Author(s): Y. Kong, M. Chen

      • Abstract

      Background:
      The morbidity and mortality of lung cancer are rather high. One major metastasis pathway of lung cancer is lymph node metastasis. The incidence of axillary lymph node metastasis(ALNM) is rare, and little is known about its clinicopathological characteristics.

      Methods:
      The clinical data of 91 patients with ALNM who were treated in Zhejiang Cancer Hospital from January 1, 2007 to December 31, 2013 were retrospectively analyzed. The relevance of tumor site、local lymph node site and axillary lymph node site were checked by contingency table. Survival rates were calculated by the Kaplan-Meier method and compared by the log-rank test.

      Results:
      Lung cancer patients with ALNM were often presented with adenocarcinoma(59.3%)、peripheral tumor type(71.4%)、 pleura invasion with pleural effusion(48.4%) or chest wall invasion(52.7%). There was a relationship between tumor site(P<0.001)、local lymph node site(P<0.001) and axillary lymph node site. The median survival time of lung cancer patients with ALNM was 19.02 months, 2-year survival rate is 62.64%. Patients detected with ALNM at the initial diagnose had poorer prognosis (p=0.002). Figure 1Figure 2





      Conclusion:
      ALNM from lung cancer is rare, it may be involved through direct chest wall invasion, spread from supraclavicular and mediastinal lymph node metastasis or systemic origin. Patients detected with ALNM at the initial diagnose had poorer prognosis.

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      P1.06-024 - Distinctive Patterns of Primary Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer (ID 3963)

      14:30 - 15:45  |  Author(s): D.S. Lee, S.J. Kim, Y.S. Kim, J.H. Kang

      • Abstract

      Background:
      The purpose of this study was to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV Non-small cell lung cancer (NSCLC).

      Methods:
      Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes.

      Results:
      The enrolled study cohort comprised 81% (n=346) Adenoca patients and 19% (n=81) SQ patients. The median age of the study population was 65 years (range, 30–94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age 65 years (69.1% vs 50.6%; P=0.003) and male sex (84% vs 56.4%; P<0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P<0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P=0.001), and brain metastasis (35% vs 16%; P=0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3–6) were more frequently found to have Adenoca (91.6% vs 73.4%; P<0.001). In multivariate prognostic evaluation, sex (P=0.001), age (P<0.001), histology (P<0.001), LN status (P=0.032), pleural/pericardial metastasis (P=0.003), abdomen/pelvis metastasis (P<0.001), axilla/neck metastasis (P=0.006), and treatment factors (P<0.001) remained independent prognostic factors affecting overall survival.

      Conclusion:
      We observed distinctive patterns of primary metastases and clinical outcomes according to the histological subtypes in stage IV NSCLC. Future studies need to disclose the underlying mechanism of these unique metastatic features and tumor biologies.

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      P1.06-025 - Analysis of Risk Factors for Development of Skeletal-Related Events in Women with Bone Metastases from NSCLC and Breast Cancer (ID 4933)

      14:30 - 15:45  |  Author(s): F. Lumachi, P. Ubiali, A. Del Conte, F. Mazza, S.M. Basso

      • Abstract
      • Slides

      Background:
      Bone metastasis (BM) are common (up to 50% of cases) in patients with advanced non-small cell lung cancer (NSCLC) and other malignancies, including prostate cancer and breast cancer (BC). In patients with BMs, the onset of skeletal-related events (SREs), such as pathological fracture, malignant hypercalcemia, or spinal cord compression requiring surgery or radiation therapy, seriously affects the quality of life of patients and overall survival. The purpose of this study was to analyze the risk factors (RFs) for development of SREs in women with advanced NSCLC and BC, with the aim of highlighting the differences (if any) between the two groups of patients.

      Methods:
      The medical records of 16 women with BMs from NSCLC (Group A) and 15 women with BMs from luminal-type BC (Group B) were reviewed. The following RFs have been considered: age >65 years, ECOG performance status (PS) <2, the presence of extra-skeletal metastases (ESM) or hypercalcemia (>2.65 mmol/L), and number of BMs >1. Odds ratio (OR) estimates and the relative 95% confidence interval (CI) were calculated. A p-value level <0.05 was considered statistically significant.

      Results:
      During follow-up, 5 (33.3%) Group A and 111 (68.7%) Group B patients developed SREs (OR=4.40, p=0.04), respectively. The results are reported in the Table. No significant difference (p=NS) was found between groups in relation to ECOG-PS, ESM or hypercalcemia, and number of BMs. Only the age >65 years (OR=0.22, p=0.04) represented a weak significant risk factor.

      Parameter NSCLC BC OR 95% CI p-value
      No. of patients 15 16 - - -
      Skeletal-related events 33.3% 68.7% 4.40 0.97-19.85 0.04
      Age >65 years 73.3% 37.5% 0.22 0.05-1.01 0.04
      ECOG-Performance status >2 40.0% 18.8% 0.34 0.07-1.76 0.25
      Extra-skeletal metastases 26.7% 43.7% 2.14 0.47-9.70 0.32
      Malignant hypercalcemia 26.7% 12.5% 0.39 0.06-2.55 0.39
      Multiple bone metastases 53.5% 37.5% 0.52 0.12-2.20 0.38


      Conclusion:
      Women with BMs from NSCLC has a reduced risk for development of SREs compared to those with BC, but elderly (>65 years) patients require a closer surveillance, and a precocious bisphosphonate treatment could be suggested.

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      P1.06-026 - Adenosquamous Carcinoma of the Lung: A Single Institution Experience in the Era of Molecular Testing (ID 6103)

      14:30 - 15:45  |  Author(s): K.K. Mandalapu

      • Abstract
      • Slides

      Background:
      Adenosquamous carcinoma (ADS) lung is rare subtype of non-small cell lung cancer (NSCLC) that compromises 0.4-4% of all lung cancers and is thought to carry a worse prognosis than adenocarcinoma (AD) or squamous cell carcinoma (SC). Epidermal growth factor receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) mutations have been observed in patients (pts) with this rare subtype. In the recent years EGFR tyrosine kinase inhibitors (Gefitinib, Afatinib and Erlotinib) and ALK inhibitors (Critzotinib, Ceritinib) have prolonged progression free survival in high-stage adenocarcinomas of the lung. The current NCCN guidelines recommend EGFR and ALK mutation testing in metastatic ADS lung cancer patients. However the frequency of these mutations as well as outcomes of patients with ADS lung is not known in this era of targeted therapies

      Methods:
      We retrospectively identified all pts seen in our oncology clinic for ADS during the last 10 years (1/1/2005 - 1/1/2015). Overall survival (OS) was estimated by Kaplan-Meier methods

      Results:
      16 pts were identified, median age at diagnosis was 71y (52-85y), 63% male, 81% had a smoking history, 87% had ECOG performance status 0-1. 37% had Stage I, 18% had stage II, 18% had stage III and 25% had stage IV disease at diagnosis, 13% developed metastatic disease after treatment for stage III disease. 75% of pts diagnosed with metastatic disease after 2012 were tested for EGFR and ALK, while none diagnosed prior to 2012 were tested. All pts were negative for EGFR and ALK mutations. All pts with Stage I and II received only surgery; pts with stage III got multimodality treatment with chemotherapy, radiation, and surgery. All the pts with metastatic disease received chemotherapy, with regimens similar to those for AD or SC of lung. The median OS for pts with localized disease was 48.3 months (48.0- NA). The median OS for pts with metastatic disease was 5.4 months (2.3-9.2)

      Conclusion:
      Our small analysis showed that pts with localized ADS of lung had similar outcomes to those of historical pts with localized AD or SC of the lung. However, pts with metastatic ADS of the lung had worse outcomes than historical pts with metastatic AD or SC of the lung even with similar chemotherapy regimens. Few pts had EGFR and ALK testing, but this is becoming more routine as we have better targeted therapies if they carry mutation

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      P1.06-027 - Retrospective Study of Treatment for Postoperative Local Recurrence of Lung Cancer (ID 4690)

      14:30 - 15:45  |  Author(s): K. Tsuruoka, K. Miyoshi, N. Matsunaga, T. Nakamura, S. Yoshida, Y. Tamura, M. Imanishi, S. Ikeda, Y. Fujisaka, I. Goto

      • Abstract
      • Slides

      Background:
      There is no consensus regarding the standard treatment for postoperative local recurrence of lung cancer. In order to clarify the impact of differences in treatment on patient survival, we conducted a retrospective study of treatment outcomes for patients with postoperative local recurrence of lung cancer.

      Methods:
      The subjects of this study were patients who were diagnosed with postoperative local recurrence of lung cancer and treated at our hospital from 2008 to 2014. We divided patients according to treatment regimen, and compared patient characteristics and survival.

      Results:
      This study included 38 patients. Among them, 8 received radiation therapy (RT), 10 received chemoradiation therapy (CRT), 18 received chemotherapy (CT), and 2 received best supportive care. The patient characteristics were as follows: median age (range), 71 years (55–84); gender male/female, 30/8; pStage at operation IA/IB/IIA/IIB/IIIA/IIIB, 9/6/9/8/5/1; histology small cell carcinoma/squamous cell carcinoma/adenocarcinoma, 5/12/21. There were no significant differences in patient characteristics between each treatment group. The proportion of patients who experienced disease progression after treatment was 75.0% (6/8) in the RT group, 20.0% (2/10) in the CRT group, and 77.8% (14/18) in the CT group. Progression free survival (PFS) tended to be better in the CRT group than in the other treatment groups. The differences in median PFS (months) were; RT vs CRT: 8.0 vs 15.5, HR=0.210 (95%CI 0.042-1.047), P=0.057; CRT vs CT: 15.5 vs 14.0, HR=0.206 (95%CI 0.047-0.908), P=0.037.

      Conclusion:
      In patients with postoperative local recurrence of lung cancer, CRT yielded better outcomes than the other treatments in terms of PFS.

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      P1.06-028 - Description of the Patients with Advanced Squamous NSCLC Treated in a Single Institution (ID 6171)

      14:30 - 15:45  |  Author(s): I. Torres, J. Gimeno, I. Pajares, A. Comin, J. Hernando, P. Felices, A. Nuño, E. Millastre, A. Viñaras, A. Artal Cortes

      • Abstract

      Background:
      Squamous carcinomas are a distinct subtype of NSCLC. Even if it is no longer the most frequent one, still remains a significant percentage of NSCLC patients in our practice. Besides, clinical presentation, associated comorbidities and available therapies are different for non-squamous subtypes. Assessing their characteristics may help to optimize therapy.

      Methods:
      DAta from patients with a diagnosis of advanced (stage IV patients plus patients with lower stages but not amenable for any local therapy) squamous NSCLand treated in our Hospital between 2009-15 were reviewed.

      Results:
      209 patients (p) were found. Median age was 69 years (40-89). Gender: Male in 89.5%. PS: ECOG 0= 9.1%, 1= 45.9%, 2= 38.3%, 3= 6.7%. By stage, I= 0.5%, II 3.4%, III 27.7%, IV 68.7%. Therapy: 29.1% of p did not receive any systemic therapy and 70.9% receive chemotherapy (CT). CT included a platinum in 69p (carboplatin 47p, cisplatin 22p) and 61p received a non-platinum scheme (gemcitabine-vinorelbine 21p, monotherapy 40 p (gemcitabine 8p, oral vinorelbine 23p, other 9p). Patients with better PS (p<0.001) and stage less than IV (0.02) were more probable to receive CT and also that CT given included platinum. Overall survival (OS) was 6.5 months (5.4-7.6) for the whole group. For stage IV patients, it was significantly shorter: 5.4 months (p=0.03). OS for patients not receiving therapy was 2.7m (vs 7.7m in those treated). Within stage IV OS was shorter for female vs male (4.2 vs 5.8m), and decreased with poorer performance status: 0, 13.5, 1, 8.2m, 2, 3.8m, 3, 2.2m.

      Conclusion:
      Squamous carcinomas are still the second most frequent subgroup of NSCLC. They are more frequently male and almost half of them presented with PS ≥2. Of them, 29% did not even receive CT and out of those treated, only 60% were considered fit to receive a platinum-based therapy. OS was generally poor, but it was remarkably low in patients with PS 2 or worse. Median OS in untreated patients was under 3 months.

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      P1.06-029 - Epidemiologic, Clinical Characteristics and Therapeutic Strategy of Elderly NSCLC Patients Treated in a Single Institution (ID 5379)

      14:30 - 15:45  |  Author(s): M. Vaslamatzis, E. Patila, T. Tegos, N. Alevizopoulos, C. Zoumblios, T. Kapou, C. Stathopoulos, A. Laskarakis, C. Zisis, E. Vasili

      • Abstract
      • Slides

      Background:
      In NSCLC pts 40% are ≥ 70y with poor PS and increased comorbidities(cbs). The aim of this retrospective study is to present all data in 208 NSCLC pts stage IIIB and IV admitted in our unit between 1/2007- 3/2016.

      Methods:
      Group A(young old):51%,70-75years(y),Group B(old):49%,75-87y.Median PS:2(0-3). Histology: Adenocarcinoma(AC) 43%, Squamous carcinoma(SCC) 31%, Adenosquamous CC 10%, Large CC 5% and Large Neuroendocrine 11%. Metastasis: Liver 79%, Bones: 72%, Adrenal: 37%, Lung: 35%, Brain: 23% of pts. Cbs included: hypertension, diabetes,heart disease, dyslipidemia, COPD, hypothyroidism, osteoporosis, Parkinson and dementia in 81, 68, 56, 56, 52, 42, 14 and 6% of pts .In Group B had ≥3 comorbidities more often (59% vs 42%), p<0.05).

      Symptoms at presentation No of pts (%) N=208 Group A% N= 106 Group B N = 102 p
      Haemoptysis 163 (78%) 78(74%) 85(83%) 0.05
      Cough 69(33%) 35(33%) 34(33%) NS
      Dyspnoea 60(29%) 22(21%) 38(37%) x<0.01
      Chest discomfort 46(22%) 17(16%) 29(28%) 0.01
      Cervical lymphadenopathy 38(18%) 18(17%) 20(19%) NS
      SVCS 27(13%) 12(11%) 15(15%) NS
      Pancoast tumors 9(4%) 4(4%) 5(5%) NS


      Results:
      Four pts(4.5%) mutated received TKI ± chemo(CT) (Paclitaxel,Carboplatin,Bevacizumab) and are still in PR for 12+, 14+, 14+, 32+, 12+ mo respectively. In 40 selected pts (≥ 80y, PS=3, ± brain metastases ± ≥5 cbs ± weight loss ≥7%) single agent was given. RR in 44% with mPFS 7(3-12)mo, mOS 11(5-16)mo. The rest received 3 cycles least of chemo ± brain RT + GCSF support: ORR: 56% in A and 49% in B. mPFS: 9(3+ - 18)mo and mOS 18(3+ - 56+)mo, 17(3+ - 56+) in A and 16 (3+ - 44+) in B. RR was 64% and 34% for pts PS 0-1 vs 2-3, p<0.001. In 720 cycles (410 and 310 in A and B),toxicity grade ≥ III: Febrile neutropenia in 11 vs 19% cycles, p <0.01, Anemia in 23 vs 27%, p=NS, Thrombocytopenia in 25 vs 30%, p=NS, Mucositis in 11 vs 15%, p=NS.

      Conclusion:
      1. When indicative CT should be given, without reduction. 2. Haemoptysis and chest discomfort are common in older pts. 3. Febrile neutropenia was the main serious side effect. 4. GCSF prophylaxis is necessary. 5. In selective patients >80y single agent seems beneficial in second line .

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      P1.06-030 - Extended Lymph Node Dissection through Median Sternotomy in N3 Left NSCLC Surgical Results and Anatomical Findings (ID 5553)

      14:30 - 15:45  |  Author(s): S. Ikeda, T. Yokota, T. Hoshino, T. Sakai

      • Abstract

      Background:
      The role of surgical approach to stage IIIA or IIIB disease surgery has been considered not appropriate. Patients with mediastinal lymph node metastasis have a poor prognosis, especially for N3 (contra lateral lymph node metastases) diseases, and lung operation is not typically indicated. We performed bilateral mediastinal lymph node dissection by median sternotomy to resect lung cancer and dissect the bilateral mediastinal lymph nodes.

      Methods:
      An extended surgical approach to bilateral neck and mediastinal nodal dissection based on the knowledge about the pathways of lymph drainage,’ systematic neck and bilateral mediastinal nodal dissection through a median sternotomy,’ beyond the anatomical difficulties would bring some improvement on the survival of the patients with N3 left NSCLC without any preoperative treatments routinely.

      Results:
      Patients with p- N3α and N3γ (neck lymph node metastases case) cases have poor prognosis, and lung operation is not normally indicated. We have performed neck and bilateral mediastinal lymph node dissection by median sternotomy to resect lung cancer and dissect the bilateral mediastinal lymph nodes. We have performed this operation in 289 patients with primary left lung cancer excluding small cell carcinoma and stageIV since 1987. 42 patients had p-N3 lymph node metastases. We will report the investigation of the prognoses of left NSCLC patients who underwent initially our extended neck and bilateral mediastinal dissection, focused on the patients with N3 disease. According to the macroscopic dissection procedure, dissection of the lymphatics from the lungs to the supraclavicular lymph nodes was performed by sequential removal of the related organs. We systematically compared and reviewed the route of lymphatic communications to the neck and contra lateral side with the anatomical significance of left-to-right lymphatic communications in the bilateral mediastinal lymph nodes. The 5-year survival rate (Kaplan-Meier method), including operative deaths and deaths due to unrelated diseases, was 48.8% in p-N3α、35.8% in N3γ.

      Conclusion:
      We found various lymphatic metastases pattern such as between neck and mediastinal lymph nodes and around the trachea in terms of clinical and anatomical status. Our surgical approach suggest the importance of the extend dissection by median sternotomy.

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      P1.06-031 - A North Malaysia Pulmonology Center Experience in Management of Advanced Non-Small Cell Lung Cancer (ID 3798)

      14:30 - 15:45  |  Author(s): S.S. Sirol Aflah, R.M.N. Md Kassim, N.M. Pathi

      • Abstract

      Background:
      Pulmonologist plays an important role not just in getting tissue sampling for diagnosis and molecular testing and staging but also administer the treatment when there is no medical oncologist available on site in some centers in some part of the world. Hence, the treatment needed to be delivered promptly to the patient under the care of pulmonologist.

      Methods:
      We retrospectively included patients who undergone palliative chemotherapy and radiotherapy with non-small cell lung cancer histology. Data were collected from clinical notes and statistical analysis was done using SPSS statistic software. The aim of the study is to look at the outcome of advanced NSCLC patients treated with palliative chemotherapy and radiotherapy with the prognostic factors.

      Results:
      In total, 86 patients were analyzed (56 male, 30 female, median age 59.36 ±12.08 with 53% of them were former and current smoker). Tissue diagnosis were obtained by endobronchial biopsy(34%), pleural biopsy (36%), CT guided (26%) and ultrasound guided transthoracic biopsy (4%).Majority tissue histology were adenocarcinoma (77.9%), squamous cell carcinoma (16.3%) and remaining was non-small cell carcinoma. Performance status of patients range from 0 to 2 (based on Eastern Cooperative Oncology Group). Among all adenocarcinoma cases,27 patients with epidermal growth factor receptor(EGFR) positive and 16 patient received oral tyrosine kinase inhibitor(TKI). The systemic chemotherapy used were Vinorelbin with Cisplatin/Carboplatin, Premetrexed, Docetaxel and Bevacizumab. All patients received first line chemotherapy(13 patients received oral TKI for first line), 24 patients received 2nd line, 6 patients on 3rd line and 3 patients on 4th line chemotherapy. 16 patients undergone concomitant radiotherapy. The median overall survival (OS) of all patients received chemotherapy was 5.16 months. The median OS were significantly longer in patients who received 2nd and 3rd line chemotherapy (12.88 month, p < 0.01 and 20.84 months, p <0.013) than 4th line chemotherapy (20.84 months, p< 0.89). Former and current smoker patient who undergone chemotherapy is 2.3 times higher risk (HR: 2.30; 95%CI: 1.35, 3.92) to die compare to non­smoker. Patients who had increase in one unit of number of chemotherapy, will reduce 47% risk to die from advanced non-small cell lung cancer (HR: 0.53; 95%CI: 0.36, 0.76). Patient who undergo radiotherapy treatment is 66% less risk(HR:0.34,95% CI:0.17,0.69) to die compared to those who did not go for radiotherapy.

      Conclusion:
      There were clinical benefits for patients received more than first line chemotherapy and radiotherapy, smoking during treatment has negative impact on survival in our cohort of patients.

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      P1.06-032 - The Humanistic Burden of Advanced Non-Small Cell Lung Cancer Patients in Europe - A Real World Survey (ID 5654)

      14:30 - 15:45  |  Author(s): G.J. Taylor-Stokes, R. Wood, B. Malcolm, M. Lees, O. Chirita

      • Abstract
      • Slides

      Background:
      Previous publications have demonstrated that advanced Non-Small Cell Lung Cancer (aNSCLC) patients have worse HRQoL compared to the general population. Few publications have focused on the impact of aNSCLC on activities of daily living and the humanistic burden incurred by different groups of aNSCLC patients in the real world setting.

      Methods:
      Data were taken from a multi-center, cross-sectional study of aNSCLC patients conducted in France, Germany and Italy. The study consisted of three components: medical chart review, patient questionnaire and caregiver questionnaire. Overall, 683 consulting patients were recruited via treating physicians. Patients’ health state was quantified using the EuroQoL-5D (EQ-5D-3L - comprising of five domains: mobility, self-care, ability to perform usual activities, pain, anxiety and depression) and the burden on HRQoL quantified using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a 30 item questionnaire yielding five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Analysis was stratified by patients’ line of therapy. Statistical significance was assessed using Mann-Whitney U tests.

      Results:
      Patients’ mean (SD) age was 65.2 (9.7), 68.8% were male and 89.0% had stage IV NSCLC. Over two-thirds (71%) of patients were receiving 1st line advanced therapy, whilst 29% were receiving later lines of therapy. Regarding histology, 74% of patients were non-squamous compared to 26% squamous. The mean EQ-5D-3L index for 2[nd] line or later patients was significantly lower compared to patients on 1[st] line treatment (0.57 vs 0.65; p=0.002). Three domains showed significant decreases: mobility, self-care and ability to perform usual activities. In terms of EORTC scores, patients on later lines of treatment experienced a lower overall global health status (QL2) compared to 1[st] line patients (43.8 vs 50.7; p<0.001). Significant differences were also observed in all other EORTC scales except for diarrhoea.

      Conclusion:
      1[st] line aNSCLC patients have a diminished health state in comparison to the general population (EQ-5D scores 0.65 v 0.78). In addition compared to other cancer sufferers, aNSCLC patients have a worse QoL (QLQ-C-30 QL2 score 48.8 v 61.5 for stage IIIB/IV cancer patients). The real world study shows that both health status and QoL significantly worsen with advancement to later lines of treatment. The results show a high unmet need for more effective 1[st]–line treatments to prevent disease progression while maintaining patient quality of life.

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      P1.06-033 - Non-Small Cell Lung Cancer in Young Patients; Clinico-Pathologic Criteria and Prognostic Factors (ID 3809)

      14:30 - 15:45  |  Author(s): M. Rahouma, H. Aziz, F. Abou Elkassem, I. Loay, G. Ghaly, M. Kamel, A.M. Abdelrahman

      • Abstract
      • Slides

      Background:
      A cancer registry was analyzed to determine the clinicopathologic characteristics and prognosis of non-small cell lung cancer (NSCLC) in patients < 45 years old at diagnosis as they were not thoroughly investigated

      Methods:
      Among enrolled NSCLC cases attending National Cancer Institute –Cairo (NCI) between 2007-2012, we retrospectively reviewed those who were 45 years old or younger. Data regarding demographics, ECCOG-performance status(PS), histology, grade, stage, chemotherapy type, number of cycles, overall and progression free survival (OS, PFS) were obtained. Pearson’s (X[2]) test , Cox regression and Kaplan-Meier survival curves were used for statistical analysis.

      Results:
      Among 99 NSCLC cases, we identified 22cases ≤ 45years. Lower stages were more prevalent among young (77.3%) versus old group(54.5%) p=0.05 Median OS in young versus old group was 18 versus 15 months(p=0.773), while PFS was 4 versus 6 months respectively (p=0.322) In our subgroup analysis(n=22); median age was 42years(30-45years), Nearly three-quarters were males, 40.9% were PS >1. The majority of cases in young group were stage IIIB(77.3.%). Pathology was squamous(40.9%), adenocarcinoma(22.7%), undifferentiated(22.7%) and adenosquamous carcinoma in 4.5% of our cases. Median OS and PFS was 18 and 4 months respectively. Significant difference in OS and PFS was observed among responder versus non responders in multivariate analysis (Figure)

      Conclusion:
      Good response to chemotherapy is the best way to prolong survival among young NSCLC cases irrespective of PS, gender, stage or pathology. Figure 1



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      P1.06-034 - Outcomes after Pulmonary Metastasectomy for Metastatic Cancer (ID 5789)

      14:30 - 15:45  |  Author(s): P. Balakrishnan, Y. Al-Sheibani, S. Galvin, B. Mahon, J. Riordan, J. McGiven

      • Abstract

      Background:
      In most malignant diseases , the ability to constantly metastasize remains a truly challenging obstacle in cancer patients . Historically in the past , any local surgical treatment in patients with systemic malignant disease is considered without any prognostic benefit , this has since evolved with many studies confering huge success rates with excellent prognostic benefits . We hereby report our experience over the last 10 years at Wellington Regional Hospital , Cardiothoracic unit .

      Methods:
      A retrospective study was undertaken in series of patients with colorectal , melanoma , breast , sarcoma & renal metastatic disease undergoing pulmonary metastasectomy , from year 2000 to 2010 . These data was identified & stratified into groups using hospital patient database & ORSOS theatre database with the aid of Excel spreadsheet .

      Results:
      All these patients were operated on either – unilateral versus bilateral , VATS or thoracotomies with or without lymph node dssection as well as repeat surgeries . The role of metastatectomy in their treatment options & the prognostic factors with impact on survival discussed .

      Conclusion:
      In carefully selected surgical patients , pulmonary metastasectomy for metastatic diseases confers continual prognostic & survival advantage for these patients .

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      P1.06-035 - Frequency and Clinical Relevance of EGFR-Mutations and EML4-ALK-Translocations in Octagenarians with NSCLC (ID 5923)

      14:30 - 15:45  |  Author(s): A. Tufman, S. Reu, S. Hasmann, D. Kauffmann-Guerrero, K. Milger, Z. Syunyaeva, K. Kahnert, R. Huber

      • Abstract

      Background:
      Novel therapies targeting genetic alterations have improved response rates and overall survival for some patients with NSCLC; however, only a minority of caucasian patients with lung cancer benefit from these treatments. Testing for EGFR mutation and ALK translocation is recommended for all patients with advanced adenocarcinoma, but the highest occurance of these driver mutations has been described in younger patients, females, and those with little or no smoking history. The frequency of driver mutations in elderly and very elderly patients has not been described.

      Methods:
      We reviewed the charts of all patients over age 70 treated at our centre in 2015 and assessed the frequency of EGFR and ALK testing. We report the frequency of EGFR and ALK alterations in patients aged 70-74 , 75-79 and >80 years.

      Results:
      Out of 179 patients diagnosed at our centre in 2015, 15 were 80 years or older at the time of first diagnosis and 7 of 15 had non-squamous histology. Among these very elderly patients, 3 patients were found to have EML4-ALK translocations and 2 patients were found to have EGFR mutation (1 Del19, 1 L858R). This represents a 71% frequency of treatable driver mutations in octagenarians with non-squamous NSCLC. Rates of genetic drivers were somewhat lower, but still clinically relevant, in non-squamous NSCLC patients aged 70-74 (27.0%) and 75-79 (26.7%).

      Conclusion:
      Very elderly patients (>80 years of age) with non-squamous NSCLC were found to have high rates of the driver alterations EGFR mutation and ALK translocation. This is clinically relevant, as this often frail and comorbid population may not be suitable for treatment with cytotoxic chemotherapy and may benefit from first line treatment with a targeted tyrosine kinase inhibitor. Testing for these genetic alterations should not be restricted to younger patients. The biology of lung cancer in the very elderly may differ from that of moderately elderly patients, as the longevity of these patients may select for individuals more resistant to, or with little exposure to, environmental carcinogens.

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      P1.06-036 - Post-Recurrence Survival Analysis of Stage I Non-Small Cell Lung Cancer: Prognostic Significance of Local Treatment (ID 5805)

      14:30 - 15:45  |  Author(s): K. Lee, H.R. Kim, D.K. Kim, Y. Kim, S. Park, S.H. Choi, S.K. Hwang, J.S. Bok, H.P. Lee, B.K. Chong

      • Abstract
      • Slides

      Background:
      The aim of this retrospective study was to review recurrence patterns of stage I non-small cell lung cancer(NSCLC), and to identify prognostic factors for post-recurrence survival(PRS).

      Methods:
      Among 940 patients with pathological stage I NSCLC who had undergone curative resection between 2001 and 2009, total 261 patients who had experienced recurrence were included in this study. Number of patients with adenocarcinoma(ADC) were 188, squamous cell carcinoma(SCC) were 62. Oligo-recurrence was defined as 1-3 loco-regional or distant recurrent lesions restricted to a single organ. Potentially-curative local treatment(PCLT) included surgery, stereotactic radiotherapy(SRT), and photodynamic therapy(PDT).

      Results:
      Median follow-up duration was 65 months(range, 4-186 months) and median disease-free interval(DFI) was 23 months(range, 2-95 months). Number of patients with oligo-recurrence was 154, and the most common sites of oligo-recurrence were lung in 84 patients, followed by brain in 18 patients, bronchial stump in 18, and single-station of mediastinal lymph nodes in 12. Local treatment for recurrent tumor included surgery in 59 patients, SRT in 50, PDT in 2, and other radiotherapy in 53. Seventy-four patients received chemotherapy only, and 36 patients took conservative treatment. Among 125 patients who were evaluated for EGFR gene mutation study, positive results was detected in 62 patients, and 31 patients were treated with TKI. The 3- and 5-year post-recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence, adenocarcinoma cell-type, DFI, TKI and PCLT were independent prognostic factors in multivariate analysis. Figure 1



      Conclusion:
      Local treatment of oligo-recurrence should be considered in selected candidates, and use of TKI is reasonable if EGFR mutation is detected.

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      P1.06-037 - Non-Small Cell Lung Cancer Invading the Diaphragm: Outcome and Prognostic Factors (ID 6240)

      14:30 - 15:45  |  Author(s): D. Galetta, L. Spaggiari

      • Abstract

      Background:
      Diaphragmatic infiltration by non-small cell lung cancer (NSCLC) is a rare occurrence and surgical results are unclear. We assessed our experience with en bloc resection of lung cancer invading the diaphragm analyzing prognostic factors and long-term outcomes.

      Methods:
      We analyzed a prospective database of patients with NSCLC infiltrating the diaphragm who underwent en bloc resection. Univariate and multivariate analysis was performed to identify prognostic factors. Survival was calculated by the Kaplan-Meier method.

      Results:
      Nineteen patients (14 men, mean age 64 years) were identified. Surgery included nine pneumonectomies, eight lobectomies, and two segmentectomies. A partial diaphragmatic infiltration was observed in 10 patients (52.6%), and full-depth invasion in nine (47.4%). Diaphragmatic reconstruction was done primarily in 13 patients (68.4%), and by prosthetic material in six (31.6%). Pathological nodal status included nine N0, four N1, and six N2. Median hospital stay was seven days (range, 4-36 days). Postoperative mortality was 5.2% (1/19). Two patients (10.5%) had major complications (acute respiratory distress syndrome and bleeding), and 10 minor complications, arrhythmia in seven (36.8%), and pneumonia in three (15.8%). Five-year survival was 29.8%. Mean survival and disease-free survival were 30 months (range, 1-164 months) and 20 months (range, 1-83 months), respectively. Factors adversely affecting survival were diaphragmatic infiltration (50% superficial vs 0% full-depth infiltration; log-rank test, P=0.04), and nodal involvement (43% N0 vs 20% N1-2; log-rank test, P=0.03).

      Conclusion:
      Resection of NSCLC invading the diaphragm is technically feasible and could be a valid therapeutic option with acceptable morbidity and mortality and long-term survival in highly selected patients.

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      P1.06-038 - Survival and Prognostic Factors of Oligometastatic Non-Small Cell Lung Carcinoma: A Single Center Experience (ID 5283)

      14:30 - 15:45  |  Author(s): D. Kızılgöz, P. Akın Kabalak, U. Yılmaz, T. İnal Cengiz, M. Karaca, E. Tunç, S.Ş.E. Gülhan, K. Wang

      • Abstract

      Background:
      In patients without targeted mutations platinum-based chemotherapy is still current treatment method with a median survival rates of 8-11 months. Patients with single side oligo-metastatic disease should be consider for curative aggressive therapies for both primary and metastatic sides for better survival (NCCN 2016).

      Methods:
      Totally 19 oligo-metastatic NSCLC patients was evaluated retrospectively by using hospital database. All patients had single metastatic side.

      Results:
      Among 19 eligible patents there was male predominance (n= 16, 84.2%). Eight patients had co-morbidities requiring regular medication. Histopathological, there were 13 (68.4%) adenocarcinoma and 6 (31.6%) non-adenocarcinoma. While brain was the most common site for metastasis 10 (52.6%), it was followed by bone (n=6, 31.6%). Treatments for primary tumour side were surgery (n=6, 31.7%), concurrent CRT (n=5, 26.3%) and sequential CRT (n=1, 5.3%). Median follow-up for whole cases were 59.1 weeks. Median overall survival (OS) and progression free survival (PFS) were 140 (±33.7) and 76 (±24.2) weeks respectively. Progressions were observed mostly in 45.4. week. Univariate cox regression analyses for OS and PFS is indicated in Table 1. Clinical T and N staging had significant relation with OS (p=0.02 and 0.03 respectively). There was no relation between bone or brain metastasis and histopathology, gender, clinical T and N staging. Median survival after first progression (SAFP) was 63 weeks (±SS 29.05). Among study parameters only clinical T staging had significant relation with SAFP (p=0.026). Median SFAP was better in patients with progression of primary tumour however median OS was better in patients with progression of distant metastasis (p>0.05).

      Factor OS PFS
      Hazard Ratio p Hazard Ratio p
      Age (cut-off=65) 1.034 (0.18-5.1) 0.96 0.4 (0.1-2.2) 0.3
      Co-morbidity 2.3 (0.54-9.8) 0.24 3.4 (0.8-14) 0.07
      Brain Metastasis 0.88 (0.21-3.6) 0.86 1.5 (0.42-5.45) 0.52
      Histopathology (adeno vs non-adeno) 0.22 (0.03-1.4) 0.10 0.67 (0.16-2.8) 0.6
      Bone Metastasis 1.78 (0.43-7.31) 0.42 1.7 (0.47-6.6) 0.4
      pN Staging (n0 and N1-2) 0.12 (0-173) 0.21 0.94 (0.22-4.02) 0.94
      cT Staging 2.17 (1-4.7) 0.02 1.11 (0.73-1.81) 0.54
      cN Staging (n0 and N1-2) 2.3 (0.86-6.6) 0.03 1.77 (0.79-3.97) 0.1
      Non-surgical curative treatment 1.88 (0.41-8.52) 0.42 1.9 (0.50-7.38) 0.34
      Surgery 0.31 (0.06-1.65) 0.14 0.21 (0.02-1.78) 0.09


      Conclusion:
      Even oligo-metastatic NSCLC means stage 4 of disease, curative treatment approaches for both primary and metastasis sides can increase patients’ prognosis than other stage 4 cases. Similar to the existed retrospective studies we had OS more than 2 years and PFS more than 1 year.

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      P1.06-039 - Retrospective Study of the Incidence and Outcomes from Lung Cancer That Developed Following a Solid Organ Transplant (ID 5136)

      14:30 - 15:45  |  Author(s): K. Young, M. Marquez, J. Yeung, F. Shepherd, S. Keshavjee, E. Renner, J. Kim, H. Ross, T. Aliev, G. Liu, N.B. Leighl, R. Feld, P.A. Bradbury

      • Abstract
      • Slides

      Background:
      Organ transplant recipients (OTR) have an increased risk of developing post-transplant malignancies with lung cancer being one of the most common. We investigated incidence and outcomes of lung cancer in OTR managed at the University Health Network.

      Methods:
      The study population, patient characteristics, treatments and outcomes were summarized from solid OTR databases, our cancer registry and patient charts from January 1, 1980 to December 31, 2015. Univariate Kaplan-Meyer curves estimated overall survival (OS) by histology, stage and chemotherapy.

      Results:
      Amongst 7994 OTR (heart [N=765], lung [n=1668], liver [n=238], kidney [n=3273]), 123 developed lung cancer (1.54%) of which (55) 44.7% occurred in lung OTR; 108 (1.35%) patients had sufficient data for subsequent analyses. Median age: 62 years (29 - 85); male: 66%; smoking status at time of transplant - former/current/never/unknown: 62%/10%/15%/8%. Histologies included non-small cell lung cancer (NSCLC): 81%; small cell lung cancer (SCLC): 10%; neuro-endocrine tumours: 9%. NSCLC: Adjuvant chemotherapy, after it became standard of care (SOC), was given to 16% of eligible NSCLC patients. At recurrence, 28% received chemotherapy while 28% received a TKI. In patients initially presenting with stage IV NSCLC, 18% received chemotherapy and 3% received a TKI. SCLC: For limited and extensive stage SCLC patients, 83% and 60% received SOC chemotherapy, respectively. All: Where chemotherapy dosing was known (n=23), 42% of patients received initial dose reductions. For early stage patients, 22% required dose reduction and 11% had chemotherapy discontinuation due to toxicity. For stage IV patients, 42% required dose reductions and 50% required discontinuations.

      Median OS by Subgroup
      Patients by Histology, Stage at Diagnosis & Systemic Treatment n median OS (months) 95% C.I.
      NSCLC: Stage I/II Systemic Treatment No treatment 48 11 37 24.9 25.7 24.9 (17.3-36.6) (14-51.6) (16.2-72.9)
      NSCLC: Stage III Systemic Treatment No treatment 7 1 6 24.6 84.0 24.6 (4.5-NA) NA (4.5-NA)
      NSCLC: Stage IV Systemic Treatment No treatment 33 7 26 3.2 8.7 2.3 (2-4) (4.7-52.4) (1.5-3.5)
      SCLC: Limited Stage Systemic Treatment No treatment 6 5 1 9.6 14.3 2.0 (2-NA) (8.4-NA) NA
      SCLC: Extensive Stage Systemic Treatment No treatment 5 3 2 1.7 5.5 0.2 (0.2-NA) (1.7-NA) (0.2-NA)


      Conclusion:
      Survival was poor in our OTR population compared to historical norms in non-transplant patients. A minority of NSCLC patients received adjuvant or palliative chemotherapy, while most SCLC patients were treated. Both often had sub-standard dosing. Chemotherapy appeared better tolerated in early stage disease.

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      P1.06-040 - Home-Based Pulmonary Rehabilitation in Advanced Non Small Cell Lung Cancer Patients Treated by Oral Targeted Therapy: A Feasibility Study (ID 4453)

      14:30 - 15:45  |  Author(s): C. Pagniez, C. Olivier, A. Olislagers, S. Peres, E. Wasielewski, A. Baranzelli, M. Willemin, X. Dhalluin, A.B. Cortot, A. Hoorelbeke, A. Scherpereel

      • Abstract
      • Slides

      Background:
      Pulmonary rehabilitation (PR) is valuable in the peri-operative setting of non small cell lung cancer (NSCLC) patients, but not established for stage IIIB-IV disease. Previously, we showed that home-based PR is feasible and may significantly improve quality of life (QoL) and functional status of NSCLC patients treated by chemotherapy (submitted). The goal of this study was to assess the feasibility and value of home-based PR in advanced NSCLC patients treated by oral targeted therapies.

      Methods:
      Advanced NSCLC patients with oral targeted therapy were recruited in a prospective study in 2015-2016 in Lille University Hospital, France. After written informed consent, they benefited from 8 weeks home-based PR including functional exercises, psychological and nutrition support, therapeutic education. Exclusion criteria were cardiovascular contraindication to PR, symptomatic brain metastasis, bone metastasis with high fracture risk, or severe cognitive disorder. Main endpoints were adherence, inclusion rate, and cause of refusal. Secondary endpoints were PR benefits assessed by QoL scales (EORTC QLQ C 30, FACT-L, HAD); functional capacity: 6min walk test, 6 min stepper test, spirometry, respiratory muscle strength; and global condition: nutrition, treatment tolerance. This study was approved by local Ethical Committee

      Results:
      Among 36 screened patients, the adhesion rate was 55.6% with 20 patients joining the study. Other patients refused mostly because (a) of “lack of interest for PR and they don’t want to be disturbed” (40% of cases), or (b) they considered “their physical activity already sufficient” (12%), or (c) “family constraints” (12%). Only 15 patients (41.6%) started PR (3 early deaths, 1 exclusion for intraventricular thrombosis, 1 consent withdrawal). No serious adverse event was reported but only grade 1 asthenia or musculoskeletal pain. Significant increases of FACT-L score from 84.7 to 100.2 (p=0.02) and 6 min stepper test from 140 to 195.7 steps (p=0.01) were found after PR, and preservation of patients’ autonomy reflected by stability of 6WT data. Most of other parameters exhibited a positive but not significant trend, likely due to the limited number of participants.

      Conclusion:
      Home-based PR is feasible and well-tolerated in patients with advanced NSCLC treated by oral targeted therapies. Significant improvements were obtained with PR based on 6ST and QoL FACT-L data. Moreover, PR was highly appreciated by patients, their relatives, and all medical teams raising our will to be able to propose PR to all our stage III-IV NSCLC patients. Currently, this study is still ongoing and multicentric, aiming at recruiting 50 extra patients.

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      P1.06-041 - Overall Survival and Intermediate Outcomes among Scandinavian Non-Small Cell Lung Cancer Patients: The SCAN-LEAF Study (ID 5141)

      14:30 - 15:45  |  Author(s): S. Ekman, J.B. Sørensen, J. Rockberg, M. Sandelin, M.M. Daumont, P. Sobocki, P. Klint, H. Huang, J. Svärd, O. Chirita, L. Jørgensen, M. Planck

      • Abstract
      • Slides

      Background:
      The past decade has seen several advances in the field of non-small cell lung cancer (NSCLC), with improved tools for tumor characterization as well as novel targeted and immune therapies. It is important to understand the current treatment landscape including treatment outcomes, in order to maximize patient benefits from these advances. SCAN-LEAF is a Scandinavian retrospective cohort study with prospective annual data cuts, providing a unique opportunity for insights into real-world clinical NSCLC practice over more than a decade. It includes clinical practice patterns of tissue biopsy, pathological diagnosis and tumor biomarker status testing, and their relationship to treatment choices and outcomes. Here, we present intermediate and survival outcomes by disease stage and histology subtype, and factors associated with survival.

      Methods:
      SCAN-LEAF consists of a registry-based cohort including all diagnosed NSCLC patients in Denmark, Norway and Sweden (Cohort 1), and a Swedish sub-cohort (Cohort 2) supplemented with data from electronic medical records (EMRs). Based on the first data collection including data from NSCLC patients diagnosed 2005-2013, overall survival (OS; Cohort 1 & 2) and progression-free survival (PFS; Cohort 2) will be estimated using Kaplan-Meier analysis and reported as cumulative incidences (with 95% CI) by disease stage at diagnosis, histological subtype, biomarker status, presence of metastases, age and gender. Response rates (Cohort 2) will be described by treatment line in addition to stage and histology subtype. Association of stage with survival (Cohort 1 & 2) and treatment response (Cohort 2) will be analyzed by Cox regression with time to event (death or response) as outcome variable and disease stage category at diagnosis, follow-up time, and therapy line as stratification variables. In addition, the relationship between OS and intermediate outcomes, as well as predictors of OS (e.g. smoking and biomarker status, lesion location, metastasis at diagnosis), will be explored by Cox regression (Cohort 2).

      Results:
      Intermediate and survival outcomes for Scandinavian NSCLC patients diagnosed between 2005 and 2013, as well as any association between overall survival and factors such as patient characteristics and treatment patterns, will be presented.

      Conclusion:
      The SCAN-LEAF study, expected to include >115,000 Scandinavian NSCLC patients and >2,000 sub-cohort patients diagnosed between 2005 and 2018 during the full duration of the study, will give valuable insights into current care, changing treatment patterns and patient outcomes in a real-world setting. A better understanding of factors associated with survival and intermediate outcomes among NSCLC patients will inform clinical decision-making.

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      P1.06-042 - The Importance of Medication Related Osteonecrosis of the Jaws (MRONJ) (ID 4309)

      14:30 - 15:45  |  Author(s): M. Krasnik, H.A. Mahedi, M. Schiodt

      • Abstract

      Background:
      Medication related osteonecrosis of the jaws (MRONJ) is an increasing problem globally, which may lead to loss of teeth and jaw bone and has a significant impact on qualtity of life. MRONJ is known since 2003, reported after antiresorptive treatment with bisphosphonate, and since 2010 also from Denosumab for skeletal metastases from breast cancer, prostate cancer and multiple myeloma, Recently, MRONJ has also been related to chemotherapy, including Tyrosine Kinase Inhibitors for lung cancer, kidney cancer and gastrointestinal cancer without skeletal metastases. The onset of MRONJ is often precipitated by of one of the above medication types in combination with a tooth extraction. Therefore it is recommended that all patients have a dental screening and relevant dental treatment before the start of medication with antiresorptives (bisphosphobnates/denosumab) or Tyrosine Kinase Inhibitors The purpose of this pstudy is to raise awareness that MRONJ can be prevented and that MRONJ also occurs among patients receiving chemotherapy without bisphosphonates or denosumab. .

      Methods:
      Rigshospitalet established the Copenhagen ONJ Cohort of consecutive patients with MRONJ since 2004, and have performed systematic prospective data collection since 2010.

      Results:
      Among 247 patients enrolled in the Copenhagen ONJ Cohort 163 had cancer and received treatment with bishosphonates in 109 cases and denosumab in 54 cases. In addition, since 2013 we have received 7 patients with MRONJ from Tyrosine Kinase inhibitors. In 85 out of 163 cancer patients (52%) the onset of MRONJ was related to tooth extraction.

      Conclusion:
      More than 50% of the MRONJ cases could potentially be avoided.If all patients had dental examination and had repaired or extracted bad teeth before start of antiresorptive medication, Thus all cancer patients should have dental examination before start of medical treatment.

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      P1.06-043 - A Study to Select Rational Therapeutics in Subjects with Advanced Malignancies (WINTHER) - The Sheba Experience in Lung Cancer Patients (ID 6414)

      14:30 - 15:45  |  Author(s): A. Onn, J. Bar, T. Sela, A. Ackerstein, S. Halperin, G. Hout-Siloni, S. Lieberman, H. Nechushatan, R. Berger

      • Abstract

      Background:
      Patient-tailored therapy based on tumor genomics is a promising tool in cancer therapy. However, in current practice it is limited to 30-40% of the patients whose tumor harbor actionable DNA mutations or amplifications

      Methods:
      : WINTHER is an open label non-randomized clinical trial developed by the WIN consortium to provide a rational personalized therapeutic choice to all (100 %) enrolled patients, irrespective of the type of genomic events. The study includes patients with metastatic cancer who progressed on at least one line of therapy. Matched tumor and normal tissue biopsies are collected from each patient and analyzed by next-generation-sequencing for known oncogenic driver aberrations (Foundation Medicine) or by functional genomics utilizing a prediction model of efficacy developed at Ben Gurion University. Based on these results study leaders from all centers make therapy decisions. The study aim is to compare progression free survival rates between the previous treatment line and the study drug/s. Patient accrual began in 2013 in four international cancer centers. The following is a description of the experience at Sheba Medical Center., specifically focusing on a large sub-population of lung cancer patients.

      Results:
      Fifty six patients were screened and biopsied for the study. The majority of patients were diagnosed with lung cancers (52%), with a diverse representation of other malignancies including breast (16%), renal (9%), colon (9%), sarcoma, bladder and head and neck. Successful biopsies yielding sufficient material for genomic analyses were achieved in 35 subjects (63%). Lung biopsy success rates were 75% and 60% respectively for normal and tumor specimens. To date, 11 lung cancer patients were treated with a variety of chemotherapy (1) or biologic agents (11) based on study recommendations while 3 have yet to progress on previous therapy. Targeted genomic alterations included EGFR (3), RET (2), KRAS (2), ALK (1), ErbB2 (1), ErbB3 (1), BRAF (1). We observed a clinical benefit rate (CBR) of 55% (6/11) with 1 subject achieving compete response (CR), 2 partial responses (PR) and 3 stable disease (SD). Subjects recruited during the second year of the study, compared to the first year had a reduced biopsy failure rate, were more likely to receive treatment and achieved an increased clinical benefit.

      Conclusion:
      The proposed strategy for tumor genomic analysis based on the comparison of matched tumor and normal biopsies is acceptable and feasible. The experience of the multidisciplinary team is an important contributor to the program’s success.

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      P1.06-044 - Costs of Adverse Events (AE) Associated with Cancer Therapies in Non-Small Cell Lung Cancer (NSCLC) in France (ID 5970)

      14:30 - 15:45  |  Author(s): C. Chouaid, D. Loirat, C. Godard, E. Clay, A. Millier, L. Lévy-Bachelot, E. Angevin

      • Abstract

      Background:
      AE associated with existing and future treatments in NSCLC are frequent and should be accounted for in health economic models. In addition to utility decrements, appropriate costing of AE management is needed. In the case of NSCLC which affects 45 200 patients per year in France, published data are scarce and not always complete. It was therefore thought of importance to assess resource use and costs associated with AEs.

      Methods:
      When looking at the grade 3 or 4 AEs appearing for at least 1% of patients in the clinical trials for erlotinib (TITAN, LUX-LUNG 8), ramucirumab plus docetaxel (REVEL), docetaxel and pembrolizumab (KEYNOTE 010), a list of 20 grade 3 and 4 AE was identified as relevant for Health Economic analysis. Among them, 7 did not have cost data available in the literature. Three French oncology experts were consulted. A questionnaire was sent before the meeting with the experts, asking for, according to the grade, insight on resource use (hospitalisation, follow-up visits, diagnosis exams, treatments). Results were discussed during the meeting in order to reach a consensus. Direct medical cost per AE, expressed in 2016 Euros, was then calculated from a national health insurance perspective based on public and private weighted tariffs and 2014 PMSI database.

      Results:
      The mean AE cost was €206 for thrombocytopenia, €263 for ocular toxic effect, €2,332 for arthralgia, €3,282 for venous thromboembolism, €3,732 for pulmonary bleeding, €5,176 for dehydration, €5,751 for pneumonia, infiltration or pneumonitis. Hospitalization costs corresponded to 46% to 100% of total AE cost. These AE costs were consistent with the costs of other grade ¾ AEs previously published for NSCLC therapies.

      Conclusion:
      Among seven grade 3 and 4 AEs seen, four appear to have an important economic impact, with a management cost of at least €3,000 per event.

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      P1.06-045 - Multiple Neoplasms Consist of Lung Cancer and Hematological Malignancies (ID 5737)

      14:30 - 15:45  |  Author(s): K. Natori, D. Nagase, S. Ishihara, Y. Mitsui, A. Sakai, Y. Kuraishi, H. Izumi

      • Abstract

      Background:
      The lung cancer is a cancer of the most in Japan and first place in cause of death. Lung cancer (LC)is still poor prognosis disease that cure only in early clinical stage. We report that we reviewed 55 cases of multiple neoplasms with lung cancer and the hematological malignancies.

      Methods:
      We intended for multiple neoplasms 339 cases including hematological malignancy. We reviewed 55 multiple neoplasms including the lung cancer. All patients were followed up until death or untile August 2016. Survival was measured from the diagnosis of multiple cancer to time of death or last contact. Definition of the multiple neoplasms in compliance with Warren & Gates. Also we determined the synchronous type and metachronous type in accordance with the definition of Moertel, so within less than 6 months was synchronous type, more than 6 months was metachronous type.

      Results:
      All cases are 55 cases, consist of male 44 cases, female 11 cases, type of multiple neoplasms, synchronous type 14 cases, metachronous type 41 cases. Number of multiple neoplasms, double neoplasms 38 cases, triple neoplasms 14 cases, quadple neoplasms 3 cases. The median age was 71years (range,47-86years) The counterpart of malignancies, MHL 26 cases, MDS 7 cases, AML 7 cases, HL 2 cases, MG 1 case, CLL 2 cases, CML 2 case, ALL 1 case, MGUS 3 cases. In double neoplasms, the median age of first diagnosis, 69years, the second cancer were 71years, About interval between lung cancer and hematological malignancies, lung cancer precedence case was 40M, hematological malignancy precedence case was 54M. The median overall survival was 24M.

      Conclusion:
      Diagnosis of LC within 5 years were 26 cases out of 41 cases. The important point is that 5 years are required for careful observation at the time of hematological malignancy diagnosis. We think that a prognosis is improved.

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      P1.06-046 - Can We Better Manage Advanced NSCLC in the Elderly with the New Therapeutic Agents? Preliminary Analysis of a Real-Life Multicenter Study (ID 5814)

      14:30 - 15:45  |  Author(s): T. Franchina, S. Novello, A. Russo, M. Gianetta, E. Capelletto, D. Galetta, A. Catino, M.R. Migliorino, S. Ricciardi, F. Morgillo, C.M. Della Corte, D. Rocco, H.J. Soto Parra, A. Russo, F. Ambrosio, V. Franchina, V. Adamo

      • Abstract
      • Slides

      Background:
      Systemic treatment of NSCLC has profoundly changed over the past years with novel therapeutic strategies recently implemented in clinical practice. Benefit of these novel agents in elderly patients (pts) is uncertain, given the paucity of prospective data in this population. Moreover, elderly pts are often undertreated, due to comorbidities and toxicity concerns. Therefore, we aimed to evaluate the access, safety and outcome with novel therapeutic agents in pts ≥ 70 years (yrs).

      Methods:
      We planned an observational study to retrospectively evaluate consecutive elderly patients (≥ 70 yrs) with metastatic NSCLC treated at 9 Italian Centers between January 2014 and December 2015. Data collected include clinical and pathological characteristics, treatment types, safety and outcome report.

      Results:
      220 patients with stage IV NSCLC were included in this preliminary analysis (53% IVa, 47% IVb). Median age was 74,5 (range 70-85) and 69% were male. 15% of pts aged 80 years or older. ECOG PS was 0, 1, 2 in 37%, 51% and 12% of pts, respectively. According to comprehensive geriatric assessment, 59% of pts were fit, 28% vulnerable and 13% frail. Histology was 23% squamous cell carcinoma, 72% non-squamous cell carcinoma and 5% NOS. EGFR mutation was diagnosed in 24% of cases; 1,4% and 1% of pts had ALK and ROS-1 translocations, respectively. 90% of pts received a systemic therapy: 48% a platinum doublet chemotherapy (CHT), 27% a mono-CHT, 25% an EGFR tyrosine kinase inhibitor (TKI). Only 1% of pts were treated with antiangiogenic drugs. Immunotherapy (IT) was administered in 16% of all treated pts. 7% of pts received only BSC. Second- and third-line treatment were given to 44% and 8% of pts, respectively. 51% of pts who received second line treatment and 60% of pts treated with a third line therapy had a novel therapeutic agent (II line TKI 20%, IT 31%; III line TKI 33%, IT 27%). 31% of pts were included in clinical trials. A dose reduction was reported in 41% of therapies and the discontinuation rate was 9%. Survival data are not mature at this time.

      Conclusion:
      Our data, albeit preliminary, suggest an evolution in the management of NSCLC in the elderly. The interesting activity and the good safety profile encourage the use of novel agents also in this setting of NSCLC. Adequate selection of elderly pts and personalized approach are still matters of debate. Use of adapted schedule and dose reduction could warrant a good compromise between safety and efficacy.

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      P1.06-047 - Management of Patients Aged over 70 Years with Newly Diagnosed Lung Cancer (ID 4159)

      14:30 - 15:45  |  Author(s): H. Abbas, M. Jafri, A. Williams, M. Jones, J. Thompson

      • Abstract

      Background:
      Lung cancer is an important cause of mortality and morbidity worldwide. It is the third most common cancer in the UK. Due to an increase in life expectancy there is an increase in the proportion of patients greater than 70 years being diagnosed with lung cancer. We looked at the management of patients diagnosed with newly diagnosed lung cancer over a period of 12 months in a large UK Teaching hospital. The main aim of this study was to compare the outcome of various treatment options offered to elderly patients diagnosed with lung cancer.

      Methods:
      All individuals diagnosed with lung cancer discussed at specialist thoracic multidisciplinary meeting aged over 70 between September 2014 and September 2015 were identified and retrospectively reviewed. Demographic data, histology, treatment and survival were evaluated

      Results:
      123 patients were included in the study, 37% were between 70-74yrs, 39% were between 75-79yrs and 48% were >= 80yrs. The commonest histology was adenocarcinoma which constituted 36.2% followed by squamous cell about 19.3%. Majority of patients were referred from hospital (57%), about 30% were referred from A&E and 12% were referred from GP. In terms of treatment; 52% received best supportive care (BSC), 30% surgery and 17% chemotherapy. Common reasons for patients receiving BSC were: poor performance status (65%), and co-morbidities (21%). Patients who had chemotherapy had improved survival compared to BSC; 5 v.s. 10 months. Node positivity was poor prognostic sign; median survival for N0, N1, N2 and N3 were 17, 10, 5 and 3 months respectively

      Conclusion:
      Treating elderly patients with lung cancer is challenging because at the time of diagnosis the tumor is often advanced and furthermore elderly patients often suffer with multiple comorbidites which makes treatment more difficult. In our cohort, patients who received active oncological treatment had improved overall survival. Majority of the patients didnt receive active oncological treatment due to poor perfomance status or co morbidites and hence not fit for treatment. Our data suggests that age should not be considered as a limiting factor for chemotherapy and there is a need for prospective studies to further evaluate active oncological management of older patients, since with careful selection this group can benefit from active treatment.

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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 55
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      P1.07-001 - A Phase II Study of Etirinotecan Pegol (NKTR-102), a Topoisomerase-l lnhibitor Polymer Conjugate, in Small Cell Lung Cancer (ID 4349)

      14:30 - 15:45  |  Author(s): H. Chen, G.K. Dy, A. Groman, W. Brady, S. Jamshed, P. Bushunow, N. Brunsing, A. Adjei

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) has poor prognosis and systemic chemotherapy is the standard treatment. Irinotecan is a topoisomerase-I inhibitor that has been used in treating SCLC. Etirinotecan pegol (NKTR-102) is a polyethylene glycol conjugate of irinotecan. It is a next generation topoisomerase-I inhibitor uniquely designed for prolonged tumor cell exposure by using the polymer conjugate technology. This is a single arm phase II study to evaluate single agent etirinotecan pegol in patients with relapsed SCLC (NCT01876446).

      Methods:
      A total of 38 patients who have received only one prior systemic therapy for SCLC are being accrued over 3 years. There are 2 patient cohorts: those progressing on first-line chemotherapy <3 months after completion of treatment (Group A: chemotherapy-resistant, N=20) and those progressing on first-line chemotherapy ≥3 months after completion of treatment (Group B: chemotherapy-sensitive, N=18). Etirinotecan pegol was administered at 145 mg/m[2] IV once every 3 weeks. Cycles were repeated every 21 days until disease progression, unacceptable toxicity, or withdrawal from study. The primary endpoint is the 18-week progression free survival (PFS) rate. The secondary endpoints are objective response rate (ORR), duration of response (DOR), overall survival (OS) and toxicity. A single-stage design is used to assess the primary endpoint separately for each patient group.

      Results:
      Accrual of Group A is ongoing. Group B has completed targeted enrollment of 18 patients and the results are presented here. Median age was 61.6 (50-76.5) years, with 50% male. Prior chemotherapy included cisplatin/etoposide (41.2%) and carboplatin/etoposide (58.8%). Patients received a median of 6 (1-30) cycles of etirinotecan pegol, with dose reduction in 22.2%. PFS rate at week 18 was 72.2% (13/18, 95% Confidence Interval (CI): 47-90%). ORR was 44.5% (8/18), including one complete response. Another one-third (6/18) of patients had stable disease. Median DOR was 4 (1.4-14.5) months. Median PFS was 21.9 (95% CI: 11.7, 29.3) weeks, and OS was 7.1 (95% CI: 4.8, 14.7) months. The most common treatment-related adverse events (AEs) of any grade were diarrhea (66.7%), nausea (55.6%), fatigue (38.9%), and vomiting (27.8%). Neutropenia occurred in 2 cases, both grade 2, without neutropenic fever. The most common AEs ≥grade 3 were lymphopenia, hyponatremia and muscular weakness (2 cases each, all grade 3).

      Conclusion:
      Etirinotecan pegol has shown promising activity with acceptable toxicity profile in treatment of chemotherapy-sensitive patients with relapsed SCLC. Accrual of chemotherapy-resistant patients is expected to be completed soon.

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      P1.07-002 - G1T28, a Cyclin Dependent Kinase 4/6 Inhibitor, in Combination with Topotecan for Previously Treated Small Cell Lung Cancer: Preliminary Results (ID 5213)

      14:30 - 15:45  |  Author(s): L.L. Hart, P.J. Roberts, R. Ferrarotto, R. Bordoni, P. Conkling, T. Patil, C.M.S. Rocha Lima, T.K. Owonikoko, S.R. Schuster, R. Jotte, R. Hoyer, K. Stabler, K.M. Makhuli, R. Aljumaily, W.J. Edenfield, A. Spira, R.K. Malik, G.I. Shapiro

      • Abstract

      Background:
      Chemotherapy-induced bone marrow and immune system toxicity causes significant acute and long-term consequences. G1T28 is a potent and selective CDK4/6 inhibitor (CDK4/6i) in development to reduce chemotherapy-induced myelosuppression and preserve immune system function in small cell lung cancer (SCLC) patients. Hematopoietic stem and progenitor cells (HSPC) are dependent upon CDK4/6 for proliferation, and preclinical models demonstrated that transient G1T28-induced G~1~ cell cycle arrest renders them resistant to chemotherapy cytotoxicity, allowing faster hematopoietic recovery, preservation of long-term stem cell and immune system function, and enhancement of chemotherapy anti-tumor activity.

      Methods:
      Objectives of this ongoing multicenter Phase 1b/2a study are to assess the dose limiting toxicities (DLTs), safety, hematological profile, PK, and anti-tumor activity of G1T28 in combination with topotecan (NCT02514447). The study consists of a limited open-label, dose-finding portion (Part 1; up to 40 patients), and an open‑label, single-arm expansion portion (Part 2; 28 patients). Eligible patients had histologically/cytologically confirmed SCLC, adequate organ function, ECOG performance status 0-2, 1-2 prior lines of chemotherapy, and no symptomatic brain metastases. G1T28, at a starting dose of 200 mg/m[2] (derived from the Phase 1a healthy volunteer study and expected to maintain HSPC G1 arrest beyond topotecan exposure), was administered IV prior to IV topotecan on days 1-5 every 21-days.

      Results:
      21 patients (median age 68, 5 females, 20 white and 1 African-American) have been enrolled across 5 cohorts. DLTs due to Grade 3/4 myelotoxicity occurred in the first two cohorts and were associated with supra-therapeutic topotecan exposures due to decreased topotecan clearance by G1T28. Reducing the topotecan dose achieved exposures in the therapeutic range and was well tolerated. No episodes of febrile neutropenia or bleeding have occurred to date. For the 17 evaluable patients, there were 5 PR, 8 SD, and 4 PD. In the 6 platinum refractory patients there were 1 PR, 3 SD, and 2 PD.

      Conclusion:
      G1T28, a novel CDK4/6i, combined with topotecan for previously treated SCLC patients has been well tolerated, without any episodes of febrile neutropenia or bleeding. There are encouraging early signs of anti-tumor activity, with a response rate of 29% overall (36%, 4/11 in sensitive and 17%, 1/6 in refractory) and a clinical benefit rate (CR+PR+SD) of 76% overall (82%, 9/11 in sensitive and 67%, 4/6 in refractory). This novel approach, allowing the administration of chemotherapy with preservation of hematopoietic function and cellular immunity, could potentially improve treatment outcomes of patients with CDK4/6-independent tumors. Updated data will be presented.

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      P1.07-003 - A Phase II Study Evaluating the Combination of Everolimus with Carboplatin/Paclitaxel as 1st Line Treatment in Patients with Advanced LCNEC (ID 4370)

      14:30 - 15:45  |  Author(s): C. Grohé, W. Engel-Riedel, C. Kropf-Sanchen, V.P. Joachim, S. Gütz, J. Kollmeier, W. Eberhardt, P. Christopoulos, I. Nimmrich, C. Sieder, V. Baum, M. Serke, M. Thomas

      • Abstract
      • Slides

      Background:
      Approximately 3% of all lung cancers are made up of large cell neuroendocrine carcinoma of the lung (LCNEC). These tumors in general have a bad prognosis and currently there are only very limited treatment options, including platinum derivatives and etoposide. The PI3/AKT/mTOR pathway is known to be dysregulated in neuroendocrine tumors (NETs). Since the mTOR inhibitor RAD001 (everolimus) already has proven effectiveness in different types of NETs, we tested whether everolimus might be also an effective treatment option in advanced LCNEC patients.

      Methods:
      In this multi-center, open-label, phase II study, everolimus was combined with platin-based chemotherapy in patients with histologically confirmed stage IV LCNEC according to WHO criteria. Further inclusion criteria were measurable disease according to RECIST 1.1 and adequate bone marrow, renal, and liver function. Main exclusion criteria were symptomatic CNS metastases and prior treatment for advanced LCNEC. Enrolled patients received everolimus once a day in combination with 4 cycles of carboplatin and paclitaxel, followed by daily everolimus maintenance therapy. The primary objective was to evaluate the efficacy by assessing the proportion of progression-free patients after three months of treatment.

      Results:
      Ten German trial sites enrolled altogether 49 patients (mean age: 62 ± 9 years; 71% men). The primary endpoint (proportion of pts progression-free at month 3) was achieved by 24 patients (49%), assessed by an independent central imaging reviewer. Further efficacy evaluation showed an overall response rate (ORR) until month 3 of 45%, a disease control rate (DCR) until month 3 of 73.5%, a median progression-free survival (PFS) of 4.3 months, and a median overall survival (OS) of 9.8 months. At least one toxicity occurred in 86% of all enrolled patients with grade 3/4 toxicities in 51%. Most frequent toxicities were diarrhea, fatigue, anemia, and neutropenia.

      Conclusion:
      The results show that a combined therapy of carboplatin and paclitaxel with the mTOR inhibitor everolimus is an alternative treatment option for LCNEC patients. When comparing to other trials, the effectiveness is comparable to a treatment regimen of cisplatin and etoposide.

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      P1.07-004 - Updated Analysis of Phase II Study of HA-Irinotecan, a CD44-Targeting Formulation of Hyaluronic Acid and Irinotecan, in Small Cell Lung Cancer (ID 5868)

      14:30 - 15:45  |  Author(s): M. Alamgeer, P. Briggs, B. Markman, P. Midolo, N. Watkins, B. Kumar, V. Ganju

      • Abstract

      Background:
      Preclinical studies in small cell lung cancer cell (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver irinotecan and selectively decrease CD44 expressing (stem cell-like) tumour cells. The current “proof of principle” study was aimed to replicate these findings by investigating the effect on clinical outcome according to CD44 expression. Final efficacy and bio-marker data on the study is presented.

      Methods:
      Patients with ESLC, having measurable disease, suitable for safe biopsy and able to give informed consent were screened for this study. First 5 patients were treated with HA-irinotecan (150mg/m[2]) and carboplatin (AUC 5), every 3 weeks to evaluate safety data. Subsequent patients were stratified as first line or second line. All second line patients receive open label HA-irinotecan, while first line patients are randomized to receive either HA-irinotecan/carboplatin or irinotecan/carboplatin. The response was measured by CT/PET at baseline, after 1 cycle and every 2 cycles subsequently. Baseline tumour samples were stained for CD44s (standard) and CD44v6 (variant 6). Blood samples for circulating tumour cells (CTCs) were also obtained at the baseline and before each treatment cycle till progression of disease.

      Results:
      Forty (40) patients, median age 66 (range 39-83) were enrolled treated on this study. Seven (7) patients either died or progressed before the first evaluation scan. Of 34 evaluable patients, the overall response rate was 50%, with 4 (12%) complete and 13 (38%) partial responses. Four patients (12%) achieved stable disease while 7 patients (20%) progressed during the treatment. There was no PFS difference in the two first line treatment arms (median 28 weeks in experimental vs 42 week in standard arm) (P = 0.892 HR=0.93, 95% CI 0.36-2042). Median PFS was 14.4 weeks in the second line cohort. The toxicity profile was similar to standard irinotecan, with the incidence of grade III/IV diarrhea seen in the experimental arm of 11% compared with 25% in the standard arm. Biomarker data was available in case of 24 patients, which suggested that there was no difference in response rates or survival according to baseline CD44s or CD44v6 expression. A possible correlation between the number of CTCs and tumour response and relapse was noticed.

      Conclusion:
      HA-irinotecan is well tolerated and has shown activity in the treatment of extensive stage small cell lung cancer. However, no improvement in efficacy was seen in CD44s+ or CD44v6+ SCLC treated with HA-irinotecan. Further strategies to combine HA with other chemotherapeutic agents may be warranted.

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      P1.07-005 - A Retrospective Study of Sequential Chemoradiotherapy for LD-SCLC Patients in Whom Concurrent Therapy is Not Indicated (ID 4066)

      14:30 - 15:45  |  Author(s): S. Ohara, S. Kanda, K. Goto, H. Shiraishi, H. Okuma, K. Itahashi, Y. Goto, H. Horinouchi, Y. Fujiwara, H. Nokihara, Y. Ito, N. Yamamoto, K. Usui, Y. Ohe

      • Abstract
      • Slides

      Background:
      The standard treatment for limited-disease small-cell lung cancer (LD-SCLC) is a combination of cisplatin-doublet chemotherapy and concurrent thoracic radiotherapy. However, sequential radiotherapy, rather than concurrent radiotherapy, is selected for some cases because of concerns regarding the irradiation field, patient age, comorbidities, or performance status. Nevertheless, the efficacy of sequential chemoradiotherapy in patients in whom concurrent chemoradiotherapy is contraindicated is not well known.

      Methods:
      We retrospectively analyzed 286 patients with LD-SCLC at the National Cancer Center Hospital and the NTT Medical Center in Japan between 2000 and 2014. We then compared the clinical characteristics and treatment outcomes of patients undergoing sequential radiotherapy with those undergoing concurrent radiotherapy.

      Results:
      One hundred and eighty-three patients received concurrent chemoradiotherapy and 30 received sequential chemoradiotherapy. The median age of the patients was 64 years (range, 18-81 years) for the concurrent group and 71.5 years (50-83 years) for the sequential group. The concurrent group contained 43 women (23%), while the sequential group contained 9 women (30%). The major reasons for the selection of sequential radiotherapy were patient age (13 patients), a large irradiation field (8 patients), and comorbidities (5 patients). In the sequential group, 23 (77%) received conventional radiotherapy, whereas 7 (23%) received accelerated hyperfractionated radiotherapy. The median overall survival period was 34.5 months for the concurrent group and 27.6 months for the sequential group (P = 0.39). The 2-, 3-, and 5-year survival rates were 71%, 50%, and 40% for the concurrent group and 56%, 56%, and 35% for the sequential group. Recurrence was seen in 149 patients (81%) in the concurrent group and 19 patients (63%) in the sequential group.

      Conclusion:
      We obtained treatment outcomes for patients who could not receive concurrent radiotherapy but could complete sequential radiotherapy that were comparable with the outcomes for those who received concurrent radiotherapy. For patients in whom concurrent chemoradiotherapy is not indicated, sequential chemoradiotherapy should be considered.

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      P1.07-006 - Preclinical Support for Evaluation of Irinotecan Liposome Injection (nal-IRI, MM-398) in Small Cell Lung Cancer (ID 4937)

      14:30 - 15:45  |  Author(s): S.C. Leonard, H. Lee, S. Klinz, N. Paz, J. Fitzgerald, B. Hendriks

      • Abstract
      • Slides

      Background:
      Nal-IRI (irinotecan liposome injection, MM-398, ONIVYDE[®]), in combination with 5-fluorouracil and leucovorin, is currently approved by the FDA for treatment of patients with advanced pancreatic cancer who have progressed on gemcitabine-based therapies. Nal-IRI is designed for extended circulation relative to non-liposomal irinotecan and to exploit leaky tumor vasculature for enhanced drug delivery to tumors. Following tumor deposition, nal-IRI is taken up by phagocytic cells followed by irinotecan release and conversion to its active metabolite SN-38 in the tumors. Sustained inhibition of topoisomerase 1 (TOP1) by extended SN-38 delivery is hypothesized to enable superior anti-tumor activity compared to traditional TOP1 inhibitors. Topotecan, a TOP1 inhibitor, is currently a standard of care for second-line treatment of small cell lung cancer (SCLC). Here, we evaluate nal-IRI compared to topotecan in preclinical models of SCLC.

      Methods:
      Anti-tumor activity of nal-IRI as a monotherapy was evaluated in DMS-53 and NCI-H1048 xenograft models. Cells were implanted subcutaneously into right flanks of NOD-SCID mice; treatments were initiated when tumors had reached approximately 280 mm[3]. Nal-IRI was dosed at 16 mg/kg salt, q1w, which is equivalent to a proposed clinical dose of 90 mg/m[2] free base, q2w. Topotecan was dosed at 0.83 mg/kg/week, Day 1-2 every 7 days, which approximates a clinical dose intensity of 1.5 mg/m[2] (Day 1-5 every 21 days). Tumor metabolite levels were compared in mice treated with nal-IRI or non-liposomal irinotecan at 24 hours post-injection, using previously established high performance liquid chromatography methods.

      Results:
      Carboxylesterase activity and sensitivity to SN-38 in mouse SCLC models were comparable to those measured in tumor types where either nal-IRI or irinotecan HCl has proven to be efficacious clinically (e.g. pancreatic cancer, colorectal cancer). Nal-IRI delivered irinotecan to SCLC tumors to a similar or greater extent than other tumor types including pancreatic tumors. The tumor irinotecan and SN-38 levels of nal-IRI (16 mg/kg salt) were 12 to 57-fold and 5 to 20-fold higher than non-liposomal irinotecan (30 mg/kg salt), respectively. Nal-IRI demonstrated anti-tumor activity in both xenograft models of SCLC at clinically relevant dose levels, and resulted in complete or partial responses after 4 cycles in NCI-H1048 or DMS-53 models, respectively, compared with topotecan which had limited tumor growth control.

      Conclusion:
      This study demonstrated that nal-IRI is more active than topotecan at clinically relevant doses in SCLC preclinical models, and thus support further clinical development of nal-IRI versus topotecan in patients with SCLC that have progressed on prior platinum-based therapy.

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      P1.07-007 - Clinical Outcomes of Patients with LS-SCLC Treated with Chemoradiotherapy. Can We Find Candidates for Salvage Surgery? (ID 5288)

      14:30 - 15:45  |  Author(s): J. Shimizu, Y. Oya, K. Tanaka, C. Kondo, H. Furuta, T. Yoshida, Y. Horio, Y. Sakao, Y. Yatabe, T. Hida

      • Abstract

      Background:
      Although small cell lung cancer (SCLC) is generally considered a systemic disease even in patients with limited stage (LS). Selected recurrent LS-SCLC patients after chemoradiation treatment have been reported long survival with receiving salvage surgery. Purpose of this study was to find candidates for salvage surgery.

      Methods:
      We retrospectively reviewed the charts of 43 consecutive patients who were treated with chemoradiotherapy for LS-SCLC at our hospital from January 2011 to December 2015 to search for the patients with locoregional progression without mediastinal lymph node involvement.

      Results:
      Of the 43 patients, the median age was 69 (38-83), 91% were male and all of them had ECOG PS 0 or 1. Clinical stage: IIA (12%), IIIA (53%), IIIB (35%). 35 (81%) received hyperfractionated RT (45Gy/30fr/3w). Objective response rate was 95%. One patient died of pneumonia. The median survival time was 1584 days and the median progression free survival was 280 days. 33 (77%) demonstrated disease progression. The first progression site was distant (include pulmonary metastasis and malignant pleural effusion) in 17, locoregional in 11, lymph node metastasis out of the radiation field in 2 and both distant and locoregional in 3. In the locoregional progression patients, 6 developed mediastinal lymph node progression in their clinical courses. Finally, 5 in 33 progressive patients had locoregional progression without mediastinal lymph node progression, and were thought possible candidates for salvage surgery.

      Conclusion:
      Most of the patients experienced distant metastasis and/or mediastinal lymph node progression. About 15% of patients who presented with apparently localized disease at the primary pulmonary site after chemoradiation might become possible candidates for salvage surgery.

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      P1.07-008 - Lomustine Endoxan VP16 as Second or Further Line for Recurrent or Progressive Brain Metastases from SCLC (ID 6153)

      14:30 - 15:45  |  Author(s): C. Naltet, A. Dugué, C. Dubos, P. Dô, S. Danhier, D. Lerouge, C. Chouaid, R. Gervais

      • Abstract

      Background:
      Up to fifty percent of patients with small-cell lung cancer (SCLC) will experience brain metastases (BM) during the whole course of their disease. The oral regimen Lomustine Cyclophosphamide Etoposide (LCE) has been tested in SCLC as second line treatment and was shown to be equivalent to the intravenous regimen Cyclophosphamide Adriamycin Vincristine (Gervais R et al. Clin Lung Cancer 2015;16:100-5). This retrospective study evaluates the cerebral response rate (CRR) of this oral chemotherapy on brain metastases (BM) from SCLC relapsing after platinum-based chemotherapy.

      Methods:
      Patients with disease progression after one or more prior chemotherapy regimens for SCLC were included if they had at least one measurable BM according to RECIST 1.1, with PS<2. Patients with symptomatic BM were eligible. They were excluded if they had received previous whole brain irradiation before LCE or were receiving concomitant brain irradiation. Patients received the chemotherapy according to modalities described in the GFPC-0501 study (1). The doses were determined by a therapeutic risk level: lomustine, 80 to 120 mg on day 1, cyclophosphamide 100 mg/d, and etoposide 75 mg/d, for 6 to 14 days, every 28 days, until progression or major toxicity. Primary prophylactic granulocyte colony-stimulating factor was recommended. The primary objective was the cerebral response rate (CRR) using RECIST 1.1 .Secondary objectives included the extra-cerebral response rate (ECRR), the overall survival and the safety.

      Results:
      From 2008 to 2014 in Baclesse comprehensive cancer center, 24 patients fulfilled the inclusion criteria. The median age was 57.5 years (interquartile range [IR] 51.5–64.5). CCR was 50% while ECRR was 26% (NS, p=0.135). Interestingly, 8 of the 9 patients with neurological symptoms had symptomatic improvement. Previous treatment (chemotherapy and/or radiotherapy) for BM did not appear to have any effect on CRR (p=1.000). The hematologic toxicities were the most common side effects with neutropenia (grade ¾ : 26%) and thrombocytopenia (grade ¾ : 21%). Median overall survival was 6.3 months.

      Conclusion:
      In our study, Lomustine Cyclophosphamide Endoxan has a high activity on BM from SCLC, with a comparable extra cerebral response rate than others regimen currently used in second line setting. It has a manageable toxicity profile and the oral route allows patients with a short expectancy of life to benefit from a home-delivered treatment. We suggest that this combination should be tested in a prospective study.

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      P1.07-009 - Outcomes of Patients with Relapsed Small-Cell Lung Cancer Treated with Paclitaxel plus Gemcitabine. 10 Year-Analysis (ID 6403)

      14:30 - 15:45  |  Author(s): A.L. Ortega Granados, N. Luque Caro, J.F. Marín Pozo, N. Cárdenas Quesada, F.J. García Verdejo, D. Fernández Garay, C. De La Torre Cabrera, M. Ruiz Sanjuan, M. Fernández Navarro, C. Rosa Garrido, M.Á. Moreno Jiménez, P. Sánchez Rovira

      • Abstract

      Background:
      We conducted a retrospective study to investigate the outcome and prognostic factors of patients with relapsed SCLC who receive second or third line chemotherapy with paclitaxel plus gemcitabine, a regimen that is used in our institution since a phase II trial in 2001. We reviewed the medical records of patients with SCLC who received paclitaxel plus gemcitabine in a ten-years period, since 2005 from 2015. Overall survival (OS) from the initiation of this regimen was evaluated, plus characteristics of these patients.

      Methods:
      Patients diagnosed of SCLC were selected from our lung cancer database, and compared with our Pharmacy Department database. We selected all patients with relapsed SCLC that received therapy with paclitaxel plus gemcitabine (PG) at any moment of the disease.

      Results:
      Patient characteristics The median age of the cohort was 58 years (43–81 years). There were 69 males (83.2%) and 14 females (16.8%). 72 patients (86.7%) had a previous history of smoking. ECOG PS at relapse was 0 in 3 (3.6%), 1 in 70 (84.3%), and 2 in 10 (12.1%) patients. Fifty patients (60.2%) had extensive disease at baseline diagnosis, and the remaining 33 (38.8%) had limited disease. All patients were exposed previously to etoposide and platinum. The platinum used was cisplatin in 52 patients (60.3%) and carboplatin in 30 patients (38.7%). Previous radiation at local tumor site was received by 38 patients (45.8%). Response The response was evaluated in 78 patients. The response post‑2 months of PG was complete response in 2 patients (2.5%), partial response in 29 (37.1%), stable disease in 24 (30.7%), and progressive disease in 23 patients (30.6%). Toxicity The median number of cycles of PG received was 8 (2-28) cycles. Toxicity related cessation of treatment was required in 12 patients (14.4%). The reason for stoppage was Grade 3–4 toxicities in 8 patients (9.6%) and deterioration in PS in 4 patients (4.8%) Outcomes The median PFS was 148 days (95% CI: 30–173.5 days) while the median OS was 172 days (95% CI: 60–485 days).

      Conclusion:
      Paclitaxel plus gemcitabine it is a well tolerated regimen in relapsed SCLC in the schedule we usually use (every 2 weeks). Unless this study is retrospective, we believe that this combination can be used nowadays in these patients, if there is no clinical trial available.

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      P1.07-010 - Influence of Creatinine Clearance on Survival Parameters in Small Cell Lung Cancer Treated with Cisplatin-Based Chemotherapy Regimen (ID 5290)

      14:30 - 15:45  |  Author(s): S. Gözel, A.T. Sumbul, A.M. Sedef, A. Besen, H. Mertsoylu, C.Y. Batmaci, F. Kose

      • Abstract

      Background:
      Extensive stage Small Cell Lung Cancer (ES-SCLC) remains incurable with the current management strategies. Despite huge effort, only the small increment in overall survival has been achieved over the past 2 decades. Cisplatin-based combination chemotherapy regimen remain standard and provide high response rate with significant improvement in survival parameters compared to non-platin based regimen. Cisplatin dose was calculated by multiplying body surface area(BSA) and 60-100 according to chemotherapy protocol. Main excretion route for the cisplatin is kidney and the drug is contraindicated for the patients with creatinine clearance (CClr) below the 60 mL/min. In other words, decrease in CClr provide higher concentration of cisplatin and may increase therapeutic effect. Therefore, with this study, we try to explore whether creatinine clearance has significant effect on survival parameters or not for the ES-SCLC patients.

      Methods:
      A total 53 patients, 47 (88.7%) male and 6 (11.3%) female, were included. Mean age was 58 years-old (range 42-73). All patients were at good performance scale with normal renal function (CClr>60mL/min) treated with cisplatin (60-100 mg/m2/3wk)-etoposide (100 mg/m2/3wk) with. Mean cisplatin dose per cycle were 121 mg/3wks and 66 mg/m2/3wks. Objective response rate was 71.7%. During follow-up period 41 patients (77.4%) were death. Mean body surface area(BSA), CClr accounted by formula of MDRD and Cockcroft gault were 1.8 kg/m2, 116.6 and 118.2 mL/min. The statistical analysis failed to show significant correlation between cisplatin dose and BSA; between cisplatin dose and MDRD and Cockcroft gault with spearman’s correlation test (r: 0.258, n:53, p: 0.58; r: -0.211, n:53, p: 0.129; r: 0.048, n:53, p: 0.73). Median overall survival(OS) was 14 months (12.1-15.9, 95%CI). Statistical analysis failed to show significant effect of CClr (>120 mL/min vs <120 mL/min) on OS (p: 0.260).

      Results:
      In this study specifically included ES-SCLC patients with excellent performance score with healthy renal function but failed to show significant effect of CClr on OS.

      Conclusion:
      In conclusion, calculation of cisplatin dose according to the method including CClr like the area under the curve(AUC) may not provide better survival rate in ES-SCLC.

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      P1.07-011 - Extensive-Stage Small Cell Lung Cancer in a 13-Year-Old Male Patient Treated with Bevacizumab Followed by High-Dose Chemotherapy (ID 4310)

      14:30 - 15:45  |  Author(s): M. Yano, M. Hebiguchi, K. Kodama

      • Abstract

      Background:
      Small cell lung cancer (SCLC) is exceedingly rare in children.

      Methods:
      We herein report a pediatric case of extensive-stage SCLC in a patient who was treated with intensive chemotherapy and high-dose chemotherapy (HDC).

      Results:
      A 13-year-old male patient was admitted to our department with a three-month history of cough. Thoracic CT and MRI showed two large masses, one was a 5.8 × 4.3 × 3.9 cm primary tumor that was located close to the right middle lobe bronchus; the other was a subcarinal lymph node. Systemic PET-CT revealed multiple bone metastases. A serological analysis revealed high levels of pro-GRP (4,075 pg/mL [normal, ≤ 81 pg/mL]) and NSE (52.3 ng/mL [normal, ≤ 16.3 ng/mL]). The patient’s plasma level of VEGF was 259 pg/mL (normal, ≤ 115 pg/mL). We diagnosed the patient with SCLC based on the results of the histopathological examination of endoscopically-obtained biopsy specimens that were obtained from part of the tumor that was partially exposed on the bronchial wall. Treatment was initiated with cisplatin and irinotecan (PI). After four courses of PI therapy followed by two courses of PI plus etoposide (PIE) therapy, there was a reduction in the tumor volume and a remarkable decrease in the patient’s biomarker levels. Thereafter, we administered three courses of chemotherapy consisting of bevacizumab, cisplatin and etoposide. Furthermore, HDC with autologous peripheral blood stem cell rescue and prophylactic cranial irradiation were performed. Early recurrence appeared one month after the completion of the series of initial treatments. He died ten months after the relapse.

      Conclusion:
      The long-term prognosis of adult SCLC patients is generally poor, even if desirable initial treatment responses are obtained. In order to improve their prognosis, new trials with other anti-cancer agents should be performed. Bevacizumab, an anti-VEGF monoclonal antibody that is effective against non-SCLC, is an intriguing candidate molecular target drug that should be evaluated for SCLC. Because the value of VEGF in the present patient’s plasma was high, we were of the opinion that the administration of bevacizumab after effective chemotherapy with PI and PIE might have represented an intensive treatment that had the potential to improve his prognosis. Because intensive chemotherapy has been observed to be highly tolerable in adolescence and young adults, we expected HDC to have a greater effect on the patient’s disease. However, the intensified therapy strategy had no impact on the patient’s disease and the results were similar to those observed in elderly patients with extensive-stage SCLC.

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      P1.07-012 - Efficacy of Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Lung Cancer: Results from a French Retrospective Cohort (ID 4613)

      14:30 - 15:45  |  Author(s): M. Giaj Levra, J. Mazieres, C. Audigier Valette, O. Molinier, D. Planchard, V. Frappat, L. Ferrer, A.C. Toffart, D. Moro-Sibilot

      • Abstract
      • Slides

      Background:
      Nivolumab and pembrolizumab, two programmed death (PD)-1 immune-checkpoint–inhibitor antibodies, demonstrated superiority versus standard chemotherapy in second- third line in both squamous and non-squamous lung cancer. Large cell neuroendocrine lung cancer (LCNEC) is a rare tumour often treated as a small cell lung cancer, but there is not a standard of care after a first line progression. Aim of the study was to assess clinical efficacy of PD-1 inhibitors in these patients.

      Methods:
      We retrospectively reviewed all consecutive LCNEC stage IIIB- IV patients treated with nivolumab or pembrolizumab after platinum-based first line therapy between July 2014 and November 2015 in six French centres. Patients were followed until June 2016. The drugs were given in an early access program or a clinical trial.

      Results:
      The analysis included 10 patients with advanced stage disease. Eight patients (80%) had a stage IV disease with a median age of 59 [interquartile range (IQR) 55-62] years. The majority were males (n=9; 90%), with good performance status (0-1; 9/90%) and 50% were treated in third line or further. Three patients presented brain metastases. In 5 cases a molecular test was done, finding in one case (20%) a KRAS mutation. Patients received a first line treatment with platinum and etoposide in 8 cases (80%) with a disease control rate of 50%. Nine patients received nivolumab and the PD-L1 status was never performed, while the patient treated with pembrolizumab expressed PD-L1. Patients received a median number of 16 [IQR, 13-18] cycles, 6 showed a partial response (60%), 1 a stable disease (10%). Median PFS was 57 [24-57] weeks. Most of the patients stopped treatment due to disease progression (n=4; 80%), only one for a pulmonary interstitial pneumonia.

      Conclusion:
      Our findings suggest that the use of immune-checkpoint–inhibitors in LCNEC could be explored in a larger cohort of patients. This treatment could be considered in the scenario of a disease with limited therapeutic strategy.

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      P1.07-013 - Treatment Related Side Effects of Oral Topotecan in Small Cell Lung Cancer (ID 5000)

      14:30 - 15:45  |  Author(s): F. Popovic, M. Jakopovic, M. Samarzija, B. Čučević, S. Kukulj, M. Roglić, S. Pleština

      • Abstract

      Background:
      Lung cancer is the most common tumor in men and the second most common tumor in woman according to the latest data available from the Croatian National Cancer Registry. Approximately 20% of all lung cancers are categorized as small cell lung cancer (SCLC). Topotecan is recommended as second-line chemotherapy in treatment of SCLC. Topotecan can be administrated orally with the same effectiveness as parenteral.

      Methods:
      The aim of this study was to determine toxicity of oral topotecan in second line of chemotherapy and to establish the frequency of drug related admissions.

      Results:
      A total of 177 courses of therapy were administered to the 64 patients, 17 woman and 47 men, with SCLC patients ranging from 42 to 77 years with the mean age of 59.3. All the patients were treated in University Hospital Centre Zagreb from January 2012 to October 2015. Included patients had ECOG performance status of 0 or 1. Topotecan was administrated every 21 day, at the dose of 2.3 mg/m[2]/day, during 5 days. Average number of courses received was 2.8. Of all included patients 17 of them (26.5%) were admitted to hospital because of adverse events related to topotecan administration. The majority of patient hospitalizations (11 patients, 16.9%) was due to febrile neutropenia. Other reasons for hospitalization were severe diarrhea in 4 patients (6.2%), pneumonia in 1 patient (1.5%) and severe electrolyte imbalance in 1 patient (1.5%). Of 17 admissions to hospital 10 (58.9%) of them were after application of first chemotherapy cycle, 3 (17.6%) after second cycle and 4 (23.5%) after third cycle. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. Anemia grade 3 or 4 occurred in 13 patients (20.3%). Grade 3 or 4 thrombocytpenia occurred in 7 patients (10.9%). Grade 3 or 4 neutropenia occurred in 16 patients (25%). Of other, non-hematologic adverse effects the most serious was grade 3 or 4 diarrhea that occurred in 5 patients (7.8%).

      Conclusion:
      although admission of oral topotecan is well tolerated it is related with high rate of hospitalizations due to myelotoxicity and gastrointestinal toxicity during therapy.

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      P1.07-014 - Impact of Chemotherapy for Small Cell Lung Cancer in the Third Line and beyond, a SEER-MEDICARE Analysis (ID 4758)

      14:30 - 15:45  |  Author(s): S. Kim, C. Ragin, Z. Chen, M. Behera, R.N. Pillai, C. Steuer, C.P. Belani, F.R. Khuri, S.S. Ramalingam, T.K. Owonikoko

      • Abstract
      • Slides

      Background:
      While there is no approved third line chemotherapy option for small cell lung cancer (SCLC), empiric use of chemotherapy is common in this setting in the absence of supporting prospective data. In order to assess the potential benefit and predictors of chemotherapy use beyond the second line setting in SCLC, we analyzed the SEER-MEDICARE database.

      Methods:
      We employed data of SCLC patients diagnosed between 1985 and 2005. Univariate (UVA) association of line of chemotherapies with covariates was examined with Wilcoxon rank-sum test, chi-square or Fisher’s exact test. Multivariable (MVA) logistic regression analysis for line of therapy was conducted using the following covariates: year of diagnosis, age, gender, race, Medicare status, urban/rural location, and radiation. Survival functions were estimated by the Kaplan-Meier method and the log-rank test was used to assess for difference in overall survival (OS) stratified by line of therapy. UVA and MVA survival analyses were carried out using the Cox proportional hazards model. To further balance confounders between patients receiving different lines of therapy, propensity scores were estimated using a MVA logistic regression model to predict the receipt of 3[rd] line chemotherapy based on relevant covariates. Propensity score analysis was further conducted by including the estimated propensity score as a covariate in a Cox proportional hazards model. All analyses were done using SAS 9.3 with two-sided tests and a significant level of 0.05.

      Results:
      There were 47,351 patients with SCLC of which 23,535 (49.7 %) received chemotherapy and 10,887 (23%) received platinum-based chemotherapy. Of the platinum-treated patients, 1424 (13.1%) received additional salvage therapy of either topotecan alone (n=801) or topotecan and additional treatments as 3[rd] line and beyond (n=623). The median OS was 11, 13, 15 and 17 months respectively for patients treated with one, two, three or > 3 lines of chemotherapy respectively. Propensity score analysis showed additional lines of therapy beyond the second line was associated with a reduced risk of death (HR: 0.786; 0.729 - 0.847, p<0.001 and 0.617; 0.564 - 0.675; p<0.001 for 3[rd] line and > 3 lines of therapy respectively). Age (p=0.043) and year of diagnosis (P<0.001) were significantly associated with treatment beyond 2[nd] line topotecan on MVA analysis.

      Conclusion:
      Salvage chemotherapy is not commonly used following failure of platinum containing chemotherapy in SCLC patients. However, chemotherapy beyond the second line was associated with an incremental survival benefit in US MEDICARE-eligible SCLC patients.

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      P1.07-015 - STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC (ID 4269)

      14:30 - 15:45  |  Author(s): P. Woll, P. Gaunt, N. Steele, S. Ahmed, C. Mulatero, R. Shah, S.J. Danson, E. Hodgkinson, K. James, B. Watkins, P. Fletcher, L.J. Billingham

      • Abstract

      Background:
      STOMP (ISRCTN 73164486, CRUK/10/037, EudraCT 2010-021165-76) is a randomised, double-blind, placebo-controlled phase II trial to evaluate activity and safety of the PARP inhibitor olaparib (AstraZeneca) as maintenance treatment for patients with chemo-responsive small cell lung cancer (SCLC). Two schedules of olaparib oral tablets were investigated: 300mg twice daily (bd) or 200mg three times daily (tds).

      Methods:
      Eligible patients had pathologically confirmed SCLC with response to first line chemotherapy or chemo-radiotherapy. Patients were stratified by metastasis-status and prior radiotherapy and randomised in a 2:2:1:1 ratio to: olaparib tds, olaparib bd, placebo tds or placebo bd. Placebo arms were pooled for analyses. Primary outcome was progression-free survival (PFS). There is 80% power to detect a difference of 3 months in PFS (from 4.8 months) between treatments based on a one-sided 5% significance level. Key secondary outcome measures were overall survival (OS), adverse events (AEs) and quality of life.

      Results:
      Between November 2013 and December 2015, 220 UK patients were randomised. Arms were well balanced for stratification factors of prior radiotherapy (89% Yes) and metastasis status (66% M1) as well as sex (46% M) and age (median=64, range 42-89). Median follow-up for 31 event-free patients was 14 months (range 0–24). Median PFS was 2.6 (90%CI 1.8, 3.7), 3.6 (90%CI 3.1, 6.0) and 3.6 (90%CI 3.1, 4.7) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in PFS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.87; 90% CI 0.64, 1.18; stratified logrank p=0.29) or the tds arm (0.89; 90% CI 0.67, 1.20; p=0.43). Median OS was 8.9 (90%CI 7.0, 11.9), 9.9 (90%CI 7.6, 12.9) and 9.0 (90%CI 6.6, 11.8) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in OS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.97; 90% CI 0.69, 1.37; stratified logrank p=0.73) or the tds arm (1.05; 90% CI 0.76, 1.46; p=0.73). The most common AEs on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. 68 patients discontinued treatment citing AEs (17 placebo, 26 olaparib bd, 25 olaparib tds).

      Conclusion:
      There is no evidence that either the bd or tds regimen for olaparib improves PFS or OS in an unselected population. The AE profile for olaparib in SCLC is similar to that observed in other studies.

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      P1.07-016 - Trends, Practice Patterns and Underuse of Surgery in the Treatment of Early Stage Small Cell Lung Cancer (ID 4070)

      14:30 - 15:45  |  Author(s): E. Wakeam, T. Varghese Jr, N.B. Leighl, M. Giuliani, S.R. Finlayson, G. Darling

      • Abstract
      • Slides

      Background:
      Current National Comprehensive Cancer Network guidelines recommend pathologic mediastinal staging and surgical resection for all patients with clinically node negative T1 and T2 small cell lung cancer (SCLC), but the extent to which surgery is used for early stage SCLC is unknown.Our obejctive was to assess trends and practice patterns in the use of surgery for SCLC.

      Methods:
      Clinical stage T1 or T2N0M0 SCLC cases were identified in the National Cancer Database (NCDB), 2004 – 2013. Demographics and clinical characteristics of patients undergoing resection were analyzed. Hierarchical logistic regression was used to identify individual and hospital-level predictors of receipt of surgical therapy. Trends in the rates of surgical resection for eligible patients were analyzed over the study period.

      Results:
      9,740 patients were identified with a diagnosis of clinical T1 or T2 N0M0 SCLC. Of these, 2,210 underwent surgery (22.7%), with 1,421 (64.3%) of these patients undergoing lobectomy, 739 (33.4%) sublobar resections and 50 (2.3%) pneumonectomies. After adjustment for clinical, demographic and facility characteristics, Medicaid patients were less likely to receive surgery (OR0.65 95% CI 0.48 – 0.89, p=0.006), as were those with T2 tumors (OR0.25 CI0.22 – 0.29, p<0.0001). Academic facilities were more likely to resect eligible patients (OR 1.90 CI1.45 – 2.49, p<0.0001). Between 2004 and 2013, rates of resection more than doubled from 9.1% to 21.7%. Overall, 68.7% of patients were not offered surgery despite having no identifiable contraindication. In patients not receiving surgery, only 7% underwent pathologic mediastinal staging.Figure 1



      Conclusion:
      Although rates of resection are increasing, surgery is rarely used nationally in the treatment of potentially eligible SCLC patients. About two thirds of potentially eligible patients fail to undergo potentially curative surgery. Further study is required to address the lack of concordance between guidelines and practice.

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      P1.07-017 - Indications for Adjuvant Mediastinal Radiation in Surgically Resected Small Cell Lung Cancer (ID 4073)

      14:30 - 15:45  |  Author(s): E. Wakeam, M. Giuliani, N.B. Leighl, T. Varghese Jr, S.R. Finlayson, G. Darling

      • Abstract
      • Slides

      Background:
      Adjuvant mediastinal radiation (AMR) is an adjunctive therapy for patients with surgically resected small cell lung cancer (SCLC). However, little data guides its use. We sought to examine whether there was a survival benefit associated with AMR for resected SCLC patients and to define sub-populations who should be selected for AMR.

      Methods:
      Patients undergoing resection (lobectomy, pneumonectomy and sublobar resection) for SCLC were identified in the National Cancer Database, 2004 – 2013. Kaplan-Meier survival curves and Cox proportional hazards were used to evaluate the impact of receipt of AMR on survival. Hazard ratios were adjusted for patient comorbidity and demographic information, as well as tumor stage, grade, histology, margin status and receipt of adjuvant chemotherapy.

      Results:
      3,113 patients were identified. Those receiving AMR were younger, more likely to have greater pathologic T- and N- stage, more likely to undergo sublobar resection and have a positive margin. Kaplan-Meier curves showed better median survival for patients with N1-3 disease who received AMR. After adjustment, Cox models showed lower risk of death for N1, N2/3 and sublobar resection with AMR (HR0.79 CI0.65 – 0.96, p=0.02; HR 0.60 CI0.48 – 0.75, p<0.0001). In the overall cohort, AMR was not associated with better survival in node-negative patients. AMR was, however, associated with improved survival for patients receiving sublobar resection (HR0.72 CI0.58 – 0.92, p=0.006).Figure 1



      Conclusion:
      AMR has significant benefit for node-positive patients after resection for SCLC, especially those with pN2 or pN3. Patients undergoing sublobar resection may benefit from AMR.

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      P1.07-018 - Incidence of Brain Recurrence and Survival Outcomes in High-Grade Neuroendocrine Carcinomas of the Lung: Implications for Clinical Practice (ID 3879)

      14:30 - 15:45  |  Author(s): G. Mountzios, B. Ricciuti, R. Chiari, M. Baretti, L. Falcinelli, D. Giannarelli, A. Sidoni, L. Crinò, G. Bellezza, A. Rebonato, P. Ferolla, L. Toschi, G. Metro

      • Abstract
      • Slides

      Background:
      Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage.

      Methods:
      Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated.

      Results:
      Overall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively), (Figure 1). Histologic subtype (LCNEC vs SCLC) was an independent prognosticator in multivariate analysis. In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 moFigure 1



      Conclusion:
      Patients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.

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      P1.07-019 - Large Cell Neuroendocrine Carcinoma of the Lung: Prognostic Factors of Survival and Recurrence after R0 Surgical Resection (ID 4928)

      14:30 - 15:45  |  Author(s): M. Cattoni, E. Vallieres, L.M. Brown, A.A. Sarkeshik, S. Margaritora, A. Siciliani, P.L. Filosso, F. Guerrera, A. Imperatori, N. Rotolo, F. Farjah, G. Wandell, K. Costas, C. Mann, M. Hubka, S. Kaplan, A.S. Farivar, R.W. Aye, B.E. Louie

      • Abstract
      • Slides

      Background:
      Large cell neuroendocrine carcinomas (LCNEC) represent approximately 3% of all lung cancers. Due to this rarity, little knowledge exists about their outcome, prognosis or optimal treatment strategy. The objective of this study is to evaluate the outcomes of patients undergoing lung resection for LCNEC to identify the factors affecting survival and recurrence to help refine the optimal treatment strategy.

      Methods:
      We retrospectively reviewed 116 patients who underwent lung resection at 8 centers between 2000-2015. We excluded 18 patients: pNX(3), stage IV(5), R1-2(10). Univariate and multivariate analysis were performed to identify factors influencing disease-specific survival, overall survival and recurrence. The variables included age, gender, smoking habit, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, tumor location, tumor size, pT, pleura invasion, pN, pStage and neo/adjuvant treatments. Kaplan-Meier, Cox regression and ROC curve were used.

      Results:
      A total of 98 patients (M/F:60/38) were analyzed with a median age of 66 years (IQR=58-72). Prior to resection, 11 (11%) received induction therapy. Resections included pneumonectomy (8), bilobectomy (3), lobectomy (76) and sublobar (11) with an associated lymph node sampling (N=52, 55%) and lymphadenectomy (N=43, 45%). Adjuvant therapy was delivered in 28 (30%). Pathologic stages were I (N=40, 41%), II (N=33, 34%) and IIIA (N=25, 25%). Median follow-up was 62 (IQR=19-120) months. The 5-year disease-specific and overall survival rates were 51.6% and 42.7%. On univariate analysis, pT was associated with disease-specific and overall survival (p=0.011, p=0.028). Similarly pT was also associated on multivariate analysis with disease-specific and overall survival (p=0.044, p=0.034). The recurrence rate was 55% (2% local, 10% regional, 32% systemic, 11% not-specified). The median disease-free interval was 16 (IQR=6-80) months. Local-regional recurrence wasn’t associated with any factor on univariate analysis. Systemic recurrence was correlated with tumor size (p=0.002), pT (p=0.003) and pStage (p=0.024) on univariate analysis. Tumor size was an independent prognostic factor of systemic recurrence on multivariate analysis (p=0.001) with a threshold value of 3 cm (AUC=0.712). The 5-year disease-free survival for systemic recurrence in tumors < 3 cm or >3 cm was 75.4% and 37.8% (p=0.001). The 5-year disease-specific survival was 56.7% and 47.3% (p=0.088).

      Conclusion:
      Treatment of LCNEC with predominately surgical resection results in a respectable 5-year survival. However, a high proportion of systemic recurrence occurs. Tumors >3 cm have a higher rate of systemic recurrence and lower rate of survival suggesting that adjuvant chemotherapy may be indicated for completely resected LCNEC >3 cm.

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      P1.07-020 - Surgical Resected Small Cell Lung Cancers (SCLCs): A Monocentric Retrospective Analysis (ID 5006)

      14:30 - 15:45  |  Author(s): L. Bonanno, E. Di Liso, M. Schiavon, A. Pavan, M. Mantiero, D. Gregori, G. Comacchio, M. Fassan, I. Attili, N. Nannini, F. Calabrese, G. Natale, G. Pasello, M. Rugge, F. Rea, P. Conte

      • Abstract

      Background:
      Standard treatment for stage I-III SCLCs is chemoradiotherapy followed by prophylactic cranial irradiation, with 5-year survival rate of about 20%. Recent retrospective analyses reported benefit from surgery followed by adjuvant platinum-based chemotherapy but no randomized trials confirmed these results.

      Methods:
      A series of 365 SCLCs treated from 1996 to 2015 has been retrospectively evaluated. Among 141 evaluable patients, 61 underwent radical-intent surgery and 21 underwent chemoradiotherapy. Clinical, radiological and pathological data were reviewed and related with outcome. Mitotic count, necrosis, TP53, Bcl-2 and PD-L1 immunohistochemical expression were analyzed.

      Results:
      Median follow-up was 42 months. Among resected patients, 46 (75%) were male and median age was 68 (95% CI: 46.9-83.4) years. Seven patients (11%) underwent pneumonectomy, 43 (71%) received chemotherapy before (20%) or after (51%) surgery. Adjuvant radiotherapy was administered in 19 (31%) cases. Pathological review of resected SCLCs was performed. Median mitotic count was 59/10 hpf and extensive necrosis was found in 80% of samples. P53 (>30%), Bcl-2 (H-index >150) and PD-L1 (>5%) expression was reported in 58%, 58% and 62% of samples respectively. None of these factors significantly affected survival. A significant correlation between necrosis and mitosis (p 0.00002), and pN2 and Bcl-2 (p 0.03) was found. Median overall survival (OS) and relapse-free survival (RFS) were 62.3 (95% CI: 32.4-82.1) and 12.8 (95% CI: 6.57-47.27) months, respectively. Mortality of surgery was 0%, morbidity was 23%. Surgical margins were found positive in 8 (13%) cases. Median OS for pN0-1 patients was 65.7 (95% CI: 44.5-108) months versus 30.3 (95%CI: 12-NA) months for patients with pN2 disease (p 0.04). Multivariate analysis confirmed pN2 stage (p 0.04) and surgical margins (p 0.03) as significant prognostic factors. Among non-resected patients, the median age was 69.4 (95% CI: 54.7-84) years. Median OS and RFS were 13.4 (95% CI: 7-26.9) and 7 (95% CI: 5.9-19) months. To confirm our results, we compared outcome of patients with pN2 disease according to surgical resection. Median OS of surgically resected SCLCs was 30.3 (95% CI: 7.03-36.9), while it was 14.7 (95% CI: 12-NA) months among patients treated with chemoradiotherapy, but the comparison was not statistically significant.

      Conclusion:
      Radical-intent surgery was feasible and associated with considerable long-term survival. Mediastinal nodal involvement and non-radical surgery were the main elements able to affect OS. The expression of PDL1 was not prognostic in stage I-III SCLCs. Further prospective studies are warranted to optimize multimodal approach and selection of patients.

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      P1.07-021 - Impact on Survival of High Dose Consolidative Thoracic Radiotherapy in Extensive Stage Small Cell Lung Cancer (ID 5142)

      14:30 - 15:45  |  Author(s): J. Jové, A. Mañes, Y. Luis, G. Perez, R. Ballester, B. Gutierrez, V. Tuset, M. Caro, A. Melero, J. Molero, I. Planas, E. Luguera, A. Alvarez, S. Villà, A. Arellano

      • Abstract

      Background:
      Consolidative thoracic radiotherapy for metastatic small cell lung cancer patients who have responded to chemotherapy is controversial. Some publications suggest improved local control which could influence survival. Slotman et al. have recently published a randomized study that showed that thoracic radiotherapy improves long term survival for patients with extensive stage small cell lung cancer (ES-SCLC) who have responded to chemotherapy. Slotman also demonstrated in 2007 that prophylactic cranial irradiation in metastatic small-cell lung cancer with response to initial chemotherapy, reduces the incidence of symptomatic brain metastases and prolongs disease-free and overall survival.

      Methods:
      In our Radiation Oncology Department we have reviewed those patients with ES-SCLC (disseminated disease excluding brain metastases) who have achieved an objective response after chemotherapy, received prophylactic cranial irradiation and, after that, some of them treated with consolidative thoracic radiotherapy (CRT). Between 1995 and 2015 we have treated 68 patients, 59 men and 9 women (median age 63 years, range 42-79), with the characteristics mentioned above. Prophylactic cranial irradiation was administered at median doses of 24 Gy (range 24-36 Gy). Thoracic radiotherapy consolidation was delivered to 23 patients (33.8 %), with a median total dose of 46 Gy (range 20-54 Gy). We compared this group with the 45 patients (66.2%) who did not receive CRT.

      Results:
      Among those patients treated with CRT, 17 patients (74%) had residual disease after chemotherapy, 4 patients (17.4%) had chest progression and 2 patients (8.7%) achieved complete response. No grade 3 toxicity has been reported. Median overall survival (OS) is 18 months in patients who received CRT, compared to 10 months in those patients who have not CRT. OS after one year was 78.3% in the group of patients with CRT and 41.3% when CRT was not performed. OS after two years was 34.8% with CRT and 6.9% without CRT.

      Conclusion:
      We have found a benefit (p=0.002) in the group of patients who received CRT, compared with patients who did not, obtaining significant differences in median survival and overall survival, taking into account that a bias selection could have affected the results. In comparison with Slotman study, we have found an improved survival with higher doses of CRT, without additional severe toxicity.

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      P1.07-022 - The Role of Surgery in Combination Treatment of Patients with Small Cell Lung Cancer (ID 3870)

      14:30 - 15:45  |  Author(s): A.A. Aksarin, M.D. Ter-Ovanesov, S.M. Kopeika, A.A. Mordovskiy

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) as the most aggressive tumor deserves a special attention. The aim of this research was to define the place of surgery of patients with SCLC in order to improve the results of treatment.

      Methods:
      Clinical material for research consists of 46 patients in stage IA-IIIA with SCLC, which were radically operated in Ugra (region Russia) between 1999 and 2013. Among patients predominate males 38 (82,6%), versus females – eight (17,4%).

      Results:
      All patients underwent radical operations R0. All resection types were included (pneumonectomy, bilobectomy, and lobectomy). By 32 patients (69,6%) systematic nodal dissection (SND) was carried out, by 5 (10,9%) - mediastinal lymph node sampling (MLS) and by 9 patients mediastinal node dissection was not carried out. By SCLC combination treatment was used more often – 32 (69,6%). By that only in 8 cases additional adjuvant of thoracic radiotherapy was used. In 14 cases only surgical resection was used (30,4%). 5-year overall survival (OS) rate was 47,1%. Median survival rate was 58 months. Five-year OS rate by surgery combined with adjuvant chemotherapy was 52,1%, as compared to only surgical treatment – 35,6%. At I stage satisfactory results were achieved: 5-year OS rate was 69% (р<0,05), – that corresponds with results of treatment of patients with non-small cell lung cancer with similar stage of process. Median survival rate was not achieved. At II stage 5-year OS rate was 31%. Median survival rate was 46 months. At III stage unsatisfactory results were obtained. 5-year OS rate was 21%. Median survival rate was only 11 months.

      Conclusion:
      SCLC at I and II stages is the indication to radical treatment, mandatory including surgical resection with SND and adjuvant chemotherapy. The main method of treatment at III stage is chemotherapy or chemoradiotherapy.

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      P1.07-023 - NGS May Discriminate Extreme Long-Term versus Short-Term Survival in Patients with Stage IV Small-Cell Lung Cancer (SCLC) (ID 5660)

      14:30 - 15:45  |  Author(s): Z. Lohinai, B. Dome, G.J. Weiss

      • Abstract

      Background:
      Molecular underpinnings that may prognosticate survival and could increase our understanding of tumor progression are far less understood processes in highly aggressive malignancies such as SCLC. We aimed to describe the clinocopathological characteristics and biomarker profiling of short versus long-term SCLC survivors using the latest, most clinically actionable genomic and immunohistochemical (IHC) alterations.

      Methods:
      Consecutive 876 metastatic SCLC patients receiving standard of care therapy were evaluated between 2000 and 2013 at the National Koranyi Institute of Pulmonology. Long-term (LT) (overall survival (OS) > 24 months) and short-term (ST) survivors (OS range 2-9 weeks) with histologically confirmed stage IV SCLC were included in this retrospective analysis. DNA and RNA were isolated from FFPE tissues. A comprehensive next-generation sequencing test (NGS) was performed to analyze gene mutations, copy number variations (CNV), mRNA expression, and protein expression by IHC (PCDx, Paradigm). Multiplex sequencing analysis had coverage >5,000x. We then evaluated the associations amongst these various biomarkers and clinicopathological characteristics.

      Results:
      Four LT and 11 ST were identified for NGS. There were five mutually exclusive gene mutations, previously not described in SCLC (EP300: c.650A>G p.N217S; c.4561G>A p.E152K; ERBB4: c.949G>A p.E317K; BRCA1: c.4981G>A p.E1661N; and EGFR (ERBB1): c.2225T>C p.V742A). Mismatch repair (MMR) deficiency, CNV and PD-L1 in tumor-infiltrating lymphocytes (TIL)/tumor cells were not found in any of the samples. TOP1 was highly elevated in both groups, supporting campothecins as effective drugs in SCLC. Certain mRNA genes appeared to be linked in a similar or overlapping pathway. HENT1 (SLC29A1) with 50-79% protein concordance and survivin (BIRC5) mRNAs were high in most of the ST vs. LT. All LT survivors, but none of the ST survivors, received consolidation thoracic radiation therapy (RT) along with standard of care chemotherapy. SSTR2 mRNA expressions were higher in LT survivors (vs. ST survivors) treated with first-line platinum-etoposide. Molecular testing revealed that ST survivors treated with cyclophosphamide, epirubicin, and vincristine were not predicted to be sensitive to doxorubicin or epirubicin. LT survivors proved to be sensitive to irinotecan/topotecan and lanreotide/octreotide but not to platinum (BRCA1 and/or survivin mRNA was not present).

      Conclusion:
      Consolidation RT and certain linked pathways may discriminate between LT and ST survivors in SCLC. NGS profiling of extreme survivors may improve classification of SCLC and possibly identify clinically-relevant new targets.

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      P1.07-024 - EGFR Mutations in Small Cell Lung Cancer (SCLC): Genetic Heterogeneity and Prognostic Impact (ID 4154)

      14:30 - 15:45  |  Author(s): H. Tang, J. Zhang, X. Hu, Y. Xu, B. Dong, J. Wang, Y. Kong, H. Ma, Z. Liao, J. Zhang, L.A. Byers, D.L. Gibbons, B.S. Glisson, I. Wistuba, J. Heymach, D.R. Gomez, A. Futreal, M. Chen

      • Abstract
      • Slides

      Background:
      EGFR mutations in SCLC were first reported in cases of lung adenocarcinoma which transformed to SCLC after TKI treatment and such mutation was speculated to be a TKI resistance mechanism. Recently case reports and high throughput sequencing in a small number of samples suggested that EGFR mutations do exist in de novo SCLC. But the genetic and clinical characteristics have not been studied in large number of samples. This study aims to conduct a large scale survey of the EGFR mutations among Chinese SCLC patients, and to analyze the genetic and clinical characteristics of such mutations.

      Methods:
      Mutation status in exon 18-21 of EGFR was assessed by dideoxy-sequencing in 565 SCLC tumors treated in Zhejiang Cancer Hospital, Hangzhou, China from 2009 to 2014 and correlated with clinical parameters. Chi-square test were used to show the correlation of clinic variables with EGFR mutation. Survival analysis was performed using the Kaplan-Meier method.

      Results:
      40 instances of EGFR mutation are detected in 565 clinical samples. The mutation rate is 7.1%. Besides classic mutations E19 deletion(n=3)and E21 L858R(n=3), the rest of the mutations detected are atypical including E18 (G719D/S, G696R, S695N/D, N700D, I715F, L688F, P694L), E19(K757N, A755V, V742I, E736K, N756Y, E749K, P753L, A755T), E20 (T790M, H773R, S768R/N, R776H/C, G796D, D807N, R803W/Q, Y813C, G810S, A763T, G779D, Q791R, C781Y, N771S), E21(L858V, G874R, K867E). Among the EGFR mutation positive patients, 27.5% (11/40) are non-smokers, higher than the EGFR negative group (16.4%, 86/525). But it is not statistically significant (p=0.129). And EGFR mutation is not correlated with sex (female vs male), age (≥65y vs <65y) or clinical stages (limited stage vs extensive stage). After matching the treatment history of the EGFR mutation positive and negative patients (excluding patients who were not treated ,only treated by traditional Chinese medicine or one cycle chemotherapy or biological therapy , treatment unkown ), univariate analysis shows that the EGFR mutation positive patients have better overall survival than the EGFR negative group, with medium OS of 24.433m±4.864m vs 14.00m±0.838m respectively (p=0.018). COX regression analysis suggests that limited stage (HR=2.610), <65 years (HR=1.476) and EGFR mutation (HR=0.587, p=0. 0.039) were independently predictive of better OS.

      Conclusion:
      Among the de novo SCLC patients diagnosed, there exists a group harboring EGFR mutations, most of which are non-classic mutations. After matching the treatment history of patients, analysis reveals that EGFR mutations are predictive of better OS.

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      P1.07-025 - MiR-495 Promotes Chemoresistance of SCLC through Epithelial-Mesenchymal Transition via Etk/BMX (ID 4077)

      14:30 - 15:45  |  Author(s): L. Guo, T. Wei, W. Zhu, S. Fang, J. Zhang

      • Abstract
      • Slides

      Background:
      MiR-495 is firstly found in the brain tissues and it can regulate neuronal plasticity by affecting the expression of brain-derived neurotropic factor. Studies have shown that the function of miR-495 is still controversial in different types of cancer. For example, it serves as a tumor suppressor in MLL-rearranged leukemia, while functions as an oncogenic miRNA in breast cancer. However, whether the miR-495 serves as a tumor suppressor or an oncogene in SCLC has not been reported.

      Methods:
      In this study, we investigated whether miR-495 regulates chemoresistance of SCLC through epithelial-mesenchymal transition (EMT) via Epithelial and endothelial tyrosine kinase (Etk/BMX) using two drug resistant cell lines. The expression of miR-495 and Etk/BMX in SCLC patients were examined in 86 SCLC tissues and 60 normal lung tissues by qRT-PCR and Immunohistochemical staining.

      Results:
      Loss- and gain-of-function experiments showed miR-495 regulated cells proliferation, tumor growth and drug resistance. MiR-495 suppression or Etk/BMX elevation in SCLC specimens correlated with poor pathologic stage and survival time. The expression of Etk/BMX was one of the directly targeted genes of miR-495. Ectopic expression of Etk/BMX obviously rescued miR-495 elevation induced inhibition of drug resistance. Etk/BMX over-expression led to higher EMT mesenchymal factors (Zeb-2, Twist, Vim) and lower epithelial molecule β-catenin, while suppression of Etk/BMX was opposite. Knockdown of Zeb-2 and Twist inhibited the chemoresistance of cells.

      Conclusion:
      Our study revealed that miR-495 promoted chemoresistance of SCLC through epithelial-mesenchymal transition via Etk/BMX. MiR-495 re-expression or Etk/BMX depletion is a promising strategy for interfering with chemoresistance in SCLC.

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      P1.07-026 - Activin A is Associated with Poor Prognosis and Promotes Metastatic Growth in Small Cell Lung Cancer (ID 5888)

      14:30 - 15:45  |  Author(s): A. Rozsas, E. Lang, M.A. Hoda, T. Klikovits, I. Kovacs, S. Torok, B. Hegedus, W. Berger, W. Klepetko, M. Grusch, B. Dome, V. Laszlo

      • Abstract

      Background:
      Small cell lung cancer (SCLC) is a devastating malignancy characterized by resistance to therapy and poor clinical outcome. Therefore, identification of novel therapeutic strategies and non-invasive biomarkers that facilitate early detection and predict prognosis is urgently needed. Expression of the growth factor activin A (ActA), a member of the TGF beta superfamily, is deregulated in a number of malignancies. However, to date there is no data on the role of ActA in SCLC.

      Methods:
      In a cohort of SCLC patients (n=79) and in sex- and age-matched controls (n=66), plasma levels of ActA were measured by ELISA. The diagnostic value of plasma ActA was evaluated by ROC curve analysis. The mRNA and protein expression levels of ActA were analyzed in SCLC cell lines by qRT-PCR and by ELISA, respectively, and one of the cell lines with low baseline ActA expression was transfected with ActA and a control vector. The effect of ActA overexpression on the in vivo growth of SCLC cells was investigated in an orthotopic xenograft model.

      Results:
      Increased plasma ActA levels were found in patients with SCLC (vs. controls) and ActA levels were elevated in a TNM stage-dependent manner. Moreover, high ActA levels were associated with significantly shorter overall survival and multivariate analysis revealed that plasma ActA concentration is an independent negative prognostic factor in this patient cohort. With an area under the curve of 0.81 (95% CI: 0.74-0-0.88), circulating ActA was identified as a useful biomarker for the diagnosis of SCLC. Expression of ActA in SCLC cell lines was detected in vitro. Furthermore, ActA overexpression increased the metastatic capacity of SCLC cells in our xenograft model.

      Conclusion:
      Our findings suggest that the measurement of circulating ActA can support the diagnosis and staging of SCLC and, moreover, that it can help to predict the clinical outcome. We also conclude that ActA has a role in the aggressive behavior of this tumor type and that its potential therapeutic relevance needs to be further investigated.

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      P1.07-027 - 13-Gene Signature of EMT Reveals Impact on Invasion and Metastasis of Neuroendocrine Carcinomas of the Lung: A Preliminary Study (ID 5466)

      14:30 - 15:45  |  Author(s): T.G. Prieto, V.K. De Sá, E.R. Olivieri, E.C. Da Silva, R.M. Reis, D.M. Carraro, V.L. Capelozzi

      • Abstract
      • Slides

      Background:
      Metastasis are responsible for the death of 90% of patients with lung cancer, indicating the need to know the multiple signaling pathways involved. Neuroendocrine lung carcinomas (NELC) encompass a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and atypical carcinoid (AC), to the high-grade large cell neuroendocrine carcinoma (LCNEC) and the small cell lung carcinoma (SCLC). Low-grade NELC are indolent, while high-grade NELC invade and metastasize rapidly. Biomarkers of NELC aggressiveness remain to be determined. Epithelial to mesenchymal transition (EMT) genes profile emerge promise as indicator of invasion and metastasis. Our aim was to evaluate: (1) EMT gene expression in NELC; (2) its relationship with the histologic subtypes and (3) its impact on behavior of the tumors.

      Methods:
      Patients with SCLC (n = 10), LCNEC (n=5), AC (n=2) and TC (n=7) were included, EMT gene expression was quantified with a quantitative real-time (RT)- PCR carried out on StepOnePlus™ Real-Time PCR System (Applied Biosystems), with RT2 Profiler PCR Array System for EMT (Qiagen, Dusseldorf, Germany). Associations of the gene signature and clinicopathological features, as well as prognostic factors were evaluated.

      Results:
      A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) that was related to EMT was up-regulated in tumor-tissue from all NELC patients, mainly in those with high-grade NELC. An increased expression of DSP, TCF3 and TGFβ3 was found in SCLC compared to AC, TC and LCNEC, and associated with lymph nodes metastasis with statistical significance respectively for DSP (p=0.03 and 0.02), TCF3 (p=0.02) and marginal significance for TCF3 and TGFβ3 (p=0.08 and p=0.08). TCF3 was also associated with tobacco history (p=0.04). A significant correlation was found between enolase and IL1RN (p=0.03), chromogranin and TGFβ2 (p=0.04), synaptophysin and TGFβ1 and TGFβ2 respectively (p=0.04 and p=0.02).

      Conclusion:
      The EMT analysis identified genes involved in cell proliferation, motility, invasion and metastasis of NELC. We further inferred DSP, TCF3 and TGFβ3 as target against lung cancer metastasis and invasion, thus arising as promising therapeutic agent.

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      P1.07-028 - Dual Role of the Focal Adhesion Kinase in Small-Cell Lung Cancer (ID 5890)

      14:30 - 15:45  |  Author(s): F. Aboubakar Nana, M. Lecocq, M. Ladjemi, B. Detry, S. Dupasquier, P.P. Massion, Y. Sibille, Y. Sibille, C. Pilette, C. Pilette, S. Ocak, S. Ocak

      • Abstract
      • Slides

      Background:
      Small cell-lung cancer (SCLC) is a devastating illness with five-year overall survival as low as 5%. The molecular steps leading to SCLC development and progression are still poorly understood and this has translated into the absence of targeted therapies. Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase which regulates integrin and growth factor signaling pathways involved in cell proliferation, survival, migration, and invasion. FAK is overexpressed and/or activated in many cancers, including SCLC. We hypothesized that FAK overexpression/activation in SCLC contributes to its aggressive behavior and that FAK may represent a therapeutic target in SCLC.

      Methods:
      Two SCLC cell lines growing in suspension (NCI-H82, NCI-H146), and adherent SCLC cell lines (NCI-H196, NCI-H446) were treated with PF-228. NCI-H446 and H82 cells were stably transfected with FAK shRNA and/or FRNK using lentivirus vector. Cell proliferation was evaluated by WST-1 assay; cell cycle by flow cytometry with propidium iodide and bromodeoxyuridine; apoptosis by caspase 3 staining in flow cytometry and by cleaved PARPp85 Western blotting (WB); motility by wound healing assay; and invasion by Boyden chambers. FAK expression/activity was evaluated by WB.

      Results:
      While PF-228 did not modify total FAK expression, it decreased FAK phosphorylation (Y397). Inhibition of FAK activity by PF-228 decreased cell proliferation, DNA synthesis, induced cell cycle arrest in G2/M phases, and increased apoptosis in dose-dependently. PF-228 also decreased motility in the adherent H196-H446 cells. To confirm the specificity of the antitumoral effects of PF-228, we stably transfected SCLC cells with FAK shRNA and FRNK and then analyzed the phenotypic changes induced by these approaches. Knockdown of total FAK protein by transfection of FAK shRNA inhibited FAK activity, but did not have any effect on cell proliferation, DNA synthesis, and cell cycle. However, reintroduction of FRNK in cells stably transfected with FAK shRNA inhibited cell proliferation and DNA synthesis. Expression of FRNK decreased cell proliferation and DNA synthesis in SCLC cells.

      Conclusion:
      Inhibition of FAK activity by PF-228 in SCLC cell lines demonstrates that FAK activity is required for cell proliferation, cycle progression, survival, and motility, suggesting that FAK inhibition may represent a suitable therapeutic target for SCLC. Inhibition of FAK by a genomic approach suggests that FAK has a dual role in SCLC biology, namely (i) a pro-tumoral effect related to the kinase domain, which induces downstream signals (ii) an anti-tumoral effect mediated by the non-kinase C-terminal domain (FRNK domain), which keeps inactive other pro-tumoral effectors

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      P1.07-029 - In Vitro Effects of Pegylated Arginase in Small Cell Lung Cancer (ID 4163)

      14:30 - 15:45  |  Author(s): S. Xu, S.K. Lam, P.N.M. Cheng, J.C.M. Ho

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases. SCLC is notoriously difficult to treat with high relapse rate and the current standard treatment remains chemotherapy. Arginine is an important amino acid in normal human cells that can be replenished through urea cycle, but some tumors are arginine-auxotrophic due to deficient argininosuccinate synthetase (ASS1) and/or ornithine transcarbamylase (OTC). BCT-100 is a pegylated arginase, which converts arginine to citrulline, has demonstrated anticancer activity in human melanoma, hepatocellular carcinoma and acute myeloid leukemia. We aim to determine the in vitro effects of BCT-100 in SCLC.

      Methods:
      A panel of 7 SCLC cell lines was obtained from ATCC. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and protein expression by Western blot. Knockdown of OTC was performed using siRNA. Flow cytometry was applied to detect mitochondrial membrane depolarization (MMD).

      Results:
      The IC~50~ values of BCT-100 in H69, DMS79, H187, H209, H526, H841 and SW1271 cells were 462.9±112.2, >1000, 24.9±6.4, 8.6±0.8, 10.1±0.7, >1000 and 49.2±7.4 mU/mL respectively. Overexpression of ASS1 in H69 and DMS79 cells, and OTC in H841 cells were associated with resistance to BCT-100. Knocking down of OTC increased sensitivity of BCT-100 in H841 cells partially via apoptosis. H526 cells (BCT-100-sensitive) was selected for mechanistic study. MMD was observed in BCT-100 treatment accompanied by cytochrome c and SMAC release from mitochondria to cytosol. N-acetylcysteine (NAC) could significantly reverse apoptosis induced by BCT-100. Besides, cyclin A2, cyclin B1 and CDK7 were downregulated in a time-dependent manner. The protein expression of p-AKT and p-mTOR was increased after exposure while RAS/RAF/ERK cell signaling pathway was inhibited with BCT-100 treatment.

      Conclusion:
      SCLC cell lines with low ASS1 and OTC expression were sensitive to arginine depletion with BCT-100, mediated through oxidative stress, cell cycle arrest and apoptotic pathway.

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      P1.07-030 - Gene Signature of EMT in Neuroendocrine Lung Carcinoma: A Comparative Analysis with Adenocarcinoma and Squamous Cell Carcinoma (ID 5366)

      14:30 - 15:45  |  Author(s): T.G. Prieto, V.K. De Sá, E.R. Olivieri, E.C. Da Silva, R.M. Reis, D.M. Carraro, V.L. Capelozzi

      • Abstract
      • Slides

      Background:
      Recurrence and metastasis are responsible for 90% of the death of patients with lung cancer. Adenocarcinomas (ADc) primarily invade blood vessels with distant metastasis, whereas squamous cell carcinoma (SqCC) involves the mediastinal lymph nodes. Neuroendocrine carcinomas of low-grade (typical and atypical carcinoid) are indolent, while high-grade NE carcinoma (large cell NE and small cell carcinomas) metastasize rapidly. Biomarkers of invasiveness in lung carcinomas still cannot be definitely determined. Epithelial to mesenchymal transition (EMT) genes profile emerge promise as indicator of invasion and metastasis. Our aim was to compare EMT gene expression in NELC, ADc and SqCC and its impact on behavior of these tumors.

      Methods:
      EMT gene expression was quantified with a quantitative real-time (RT)- PCR carried out on StepOnePlus™ Real-Time PCR System (Applied Biosystems) with RT2 Profiler PCR Array System for EMT (Qiagen, Dusseldorf, Germany).

      Results:
      Younger patients expressed higher amount of AHNAK, IL1RN, MSN, TCF3 and VIM than older (p<0.05), whereas SNAI3 and TGFβ2 were more expressed in smokers (p<0.05). ADc and SqCC presented significant higher expression of COL3A1, DSP and MSN in tumor compared to normal tissue (p<0.05). 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3 and VIM) was up-regulated in tumor-tissue from all NELC patients. In ADc and NELC, AHNAK, IL1RN, TCF3 and VIM was significantly different (p<0.05). ADc and SqCC compared with high-grade NELC also presented differences in COL3A1 (p<0.01). Interestingly, only NELC expressed PDGFRB, SNAI1, SNAI3, TCF3, TGFβ1, TGFβ2, TGFβ3. Advanced tumors, usually with metastasis, showed higher expression of AHNAK, DSP, IL1RN, MSN and VIM (p<0.05), as well as association with poor outcome (p <0.01).

      Conclusion:
      Different expression of EMT gene signature in endocrine and non-endocrine lung carcinomas, its relationship with histologic types, advanced stage, lymph node metastasis and death suggest a possible role of these markers in this malignancy, but more importantly provide a potential biomolecular marker to predict outcome. The correlation between NELC, ADc, SqCC and specific EMT genes involved in cell proliferation and motility provides a possible role of these genes on the development and aggressiveness in these tumors. Moreover, the specific genes expressed only in NELC emerges as promise biomarker of behavior. Further studies are needed to validate EMT gene expression to predict prognosis and tumoral aggressiveness.

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      P1.07-031 - Clinical Evaluation of Folate Receptor-Positive Circulating Tumor Cells Detection in Patients with Small Cell Lung Cancer (ID 5480)

      14:30 - 15:45  |  Author(s): C. Su, J. Zhao, X. Li, T. Jiang, C. Zhao, W. Zhao, S. Ren, C. Zhou

      • Abstract

      Background:
      Small cell lung cancer (SCLC) is distinguished by extremely high numbers of circulating tumor cells (CTCs) in comparison to other malignancies, however, the role of CTCs in evaluating chemotherapy effect of SCLC is to be further clarified. The purpose of this study was to investigate the predictive and prognostic role of folate receptor–positive CTCs in unresectable SCLC.

      Methods:
      In this single-center prospective study, blood samples for folate receptor–positive CTCs analysis were obtained from 80 patients with chemotherapy-naive unresectable SCLC at baseline, after two cycles of chemotherapy, and on disease progression. All patients received chemotherapy with EC or EP regimen for at least two cycles. CTCs number at baseline, after chemotherapy and changes with chemotherapy were evaluated as predictive factors for chemotherapy effect, along with clinical characteristics.

      Results:
      Of all 80 patients, CTCs was detected at baseline as positive (CTCs>8.7 FU/3mL) in 67 patients, with the percentage of 83.8%, which was not associated with age, sex, smoking status or disease stage. In 72 evaluable patients, the disease control rate was 83.9% (52/62) and 50% (5/10) in CTCs positive and negative patients respectively (P=0.004). In CTCs positive patients, those harboring low levels of folate receptor (8.7
      Conclusion:
      CTCs number at baseline could be used as a useful prognostic biomarker for SCLC. Reduction in CTCs number with chemotherapy could predict better chemotherapy effect of SCLC.

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      P1.07-032 - Most Common Genomic Alterations in SCLC (ID 5112)

      14:30 - 15:45  |  Author(s): I. Bonta, R. Bechara, C. Parks, D. Miller, D. Bonta, P.L. Thompson

      • Abstract

      Background:
      Lung cancer is the leading cause of cancer death in US. The American Cancer Society’s estimates for lung cancer in the United States for 2016 are: approx 224,390 new cases of lung cancer and approx 158,080 deaths. Approximately 10-15% of lung cancers are classified as small cell (SCLC). These cancers portend a poor prognosis. Genomic sequencing of non-small cell lung cancer led to developing of new therapeutic modalities, i.e. targeted therapy with superior results to conventional cytotoxic chemotherapy. At this time, there is no approved targeted therapy for SCLC. In order to develop targeted therapies we need to identify and characterize molecular targets (alterations). This study aims to report our experience with genomic sequencing of SCLC

      Methods:
      We performed a retrospective analysis of a dataset of 54 cases of SCLC, who underwent genomic sequencing. Patients were treated at 5 tertiary referral centers, between October 2012 and June 2016. The recorded data included: age at diagnosis, date of the genomic sequencing, genomic alteration (affected genes and the type of molecular alteration identified). For genomic profiling we used a platform commercially available (FoundationOne).

      Results:
      We obtained 54 samples from 54 patients. Age range is 42 to 75 years, mean 60 and median 61 years old. All cases had a histologic diagnosis of SCLC. The genomic analysis found 88 affected genes with 230 alterations. The most common affected genes: Tp53 alteration, 45 cases (83%) and Rb1 33 cases (61%). There were an average of 4.3 mutations per patient; with a median of 4 mutations per patient, with a minimum of 0 and a maximum of 13. Figure 1



      Conclusion:
      Sustained investigations and sequencing of larger numbers of SCLC are aiming to identify potential actionable mutations in these tumors. The ultimate goal is to determine new therapies and optimal treatment strategy based on the genomic profile.

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      P1.07-033 - Trastuzumab Emtansine (T-DM1) Suppresses the Growth of HER2-Positive Small-Cell Lung Cancer in Preclinical Models (ID 3883)

      14:30 - 15:45  |  Author(s): O. Morimura, T. Minami, T. Kijima, S. Koyama, T. Otsuka, Y. Kinehara, A. Osa, M. Higashiguchi, K. Miyake, I. Nagatomo, H. Hirata, K. Iwahori, T. Takimoto, Y. Takeda, H. Kida, A. Kumanogoh

      • Abstract
      • Slides

      Background:
      To overcome chemoresistance is indispensable to bring about better prognosis in small-cell lung cancer (SCLC). We have reported that HER2 is upregulated when HER2-positive SCLC cells acquire chemoresistance. Moreover, HER2-upregulated cisplatin- or etoposide-resistant SCLC cells were sensitive to trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). However, irinotecan-resistant SCLC cells, e.g. SBC-3/SN-38, were refractory to trastuzumab despite high HER2 expression. To address this issue, we studied the antitumor efficacy of trastuzumab emtansine (T-DM1) on trastuzumab-resistant HER2-positive SCLC.

      Methods:
      SBC-3/SN-38 (HER2-positive) or OS2RA (HER2-negative) SCLC cells were inoculated subcutaneously in the flank of six-week-old male nude mice. Tumor size was measured with a caliper two or three times per week. When tumor volume reached about 150-200 mm[3], mice were randomly assigned to three treatment groups. Each group was treated with intravenous injection of T-DM1 15 mg/kg, intraperitoneal injection of trastuzumab 30 mg/kg, or saline as control. To confirm the HER2-specific delivery of T-DM1, in vivo imaging was performed. Namely, several tumor-bearing mice were intravenously administered with fluorescence-labeled T-DM1. Fluorescence images of mice were captured with IVIS® Lumina II system (PerkinElmer).

      Results:
      Treatment with T-DM1 significantly suppressed the growth of SBC-3/SN-38 xenografts compared with trastuzumab and saline groups. Histological analysis revealed that T-DM1 remarkably induced apoptosis and inhibited proliferation. Fluorescence-labeled T-DM1 definitely accumulated to the xenografts in a HER2-selective fashion.

      Conclusion:
      T-DM1 treatment could be an attractive therapeutic option in trastuzumab-resistant HER2-positive SCLC where trastuzumab cannot induce enough ADCC activity. Delivery of a cytotoxic agent DM1 to the inside of cells via HER2-mediated internalization is expected and crucial to exert antitumor effect in such ADCC-lacking SCLC cells. Figure 1



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      P1.07-034 - Somatostatin Receptors Expression in Small Cell Lung Cancer Patients (ID 5242)

      14:30 - 15:45  |  Author(s): E. Boutsikou, G. Gerasimou, D. Spyratos, E. Eleptheriadou, A. Gotzamani, K. Zarogoulidis

      • Abstract
      • Slides

      Background:
      Somatostatin receptors have been described on the membrane of neoplastic cells and their expression has also been demonstrated on small cell lung cancer (SCLC). In this study we examined if the expression of somatostatin receptors at the time of disease progression correlated with survival and time to progression (TTP) of SCLC patients.

      Methods:
      10 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy at diagnosis and disease progression. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPECT technique .The scintigraphic results were expressed in comparison with soft tissue intake (normal prices <1.5).

      Results:
      111In-OCT was positive in all 10 SCLC patients at the time of diagnosis and progression of the disease. No statistical correlation was found between somatostatin receptors expression at the progression- mainly subtype 2( SSTR 2)- and survival (p=0.43), nor TTP(p=0.25) .Also the difference in somatostatin receptors expression during diagnosis and progression had no statistical correlation with survival and TTP.

      Conclusion:
      The clinical utility of receptor status characterization obtained with 111In-OCT scintigraphy is rather confined. Our study shows that 111In-OCT scintigraphy, although is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases, cannot be used as a prognostic or predictive factor in SCLC patients.

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      P1.07-035 - Circulating Cell-Free Tumor DNA (cfDNA) Testing in Small Cell Lung Cancer (ID 6193)

      14:30 - 15:45  |  Author(s): D. Morgensztern, S. Devarakonda, A. Masood, S.N. Waqar, A.C. Carmack, K.C. Banks, R.B. Lanman, R. Govindan

      • Abstract

      Background:
      The diagnosis of small cell lung cancer (SCLC) is often made using fine needle aspiration or small biopsy of tumor specimens that are typically insufficient for next generation sequencing (NGS) analysis. Guardant360 (G360), a blood-based liquid biopsy that analyzes circulating free tumor DNA, may allow the detection of potentially targetable gene abnormalities without the need for repeated tissue biopsies.

      Methods:
      Peripheral blood samples from patients with SCLC were collected in two 10 mL tubes. Cell-free DNA was extracted and analyzed by digital sequencing for the detection of single nucleotide variants (SNVs), small Insertions and Deletions (INDELs), Copy Number Alterations (CNAs), and gene fusions. The Tumor Alterations Relevant for Genomics-Driven Therapy (TARGET) curated database (http://www.broadinstitute.org/cancer/cga/target) was queried for potentially actionable alterations.

      Results:
      240 samples from 227 de-identified patients were collected between June 2014 and June 2016. 7 patients had more than one sample analyzed. During this time period, the number of genes in the panel increased from 54 (10 samples) to 68 (87 samples) and finally to 70 (143 samples). The median time from sample collection to reporting was 13 days (range 8-28 days). Alterations in at least one gene were found in 222 (92.5%) of samples and 210 (92.5%) patients. SNVs in TP53 and RB1 were seen in 72.4% (152/210) and 25.7% (35/136) of patients with detectable alterations respectively. The most common potentially actionable alterations were amplifications of FGFR1 (11.8%) and ERBB2 (7.1%). MYC amplification, which was not considered an actionable alteration by TARGET but has been associated with sensitivity to Aurora kinase inhibitors in pre-clinical studies, was observed in 15.8% of patients. Eight patients had EGFR activating mutations (exon 21 L858R mutation or exon 19 deletion), of which 2 patients also had EGFR T790M mutation, likely representing transformation from NSCLC following targeted therapy with EGFR Tyrosine kinase inhibitors. KIF5B-ALK and AFAP1-RET fusions were seen in 1 patient each.

      Conclusion:
      G360 is a rapid non-invasive NGS platform which may be particularly useful in patients with advanced stage SCLC where tissue samples may be suboptimal for NGS. Due to the limited treatment options in this patient population, the detection of potentially actionable genes through G360 may provide valuable information to guide treatment decisions.

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      P1.07-036 - Large Cell Neuroendocrine Carcinoma of the Lung: The Mayo Clinic Experience (ID 4925)

      14:30 - 15:45  |  Author(s): K. Maneenil, M. Liu, A. Adjei, J. Molina, P. Yang

      • Abstract
      • Slides

      Background:
      Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC). LCNEC is considered aggressive, and the optimal treatment strategy and chemotherapy regimen remain undefined.

      Methods:
      We retrospectively evaluated a LCNEC patient cohort established from 1997 to 2015 at Mayo Clinic (Minnesota). A diagnosis of LCNEC was made when all WHO classification criteria were present in the tumor section examined. Clinical characteristics, treatment and outcomes were analyzed. Available radiology assessment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

      Results:
      The study included 55 LCNEC patients. Median age at diagnosis was 63 years (range: 38-88); two thirds were men; and majority were smokers (94%). Clinical staging was I, II, III or IV in 52.8%, 9.1%, 14.5%, and 23.6% of cases, respectively. Forty-six percent of stage IV patients presented with brain metastases at time of diagnosis (n=6/13) and 18% (n=7/38) developed brain recurrence in the follow up period. Thirty-nine (71%) patients had surgery and 9 (16%) patients received adjuvant platinum-based chemotherapy. Sixty-five percent of patients with complete resection experienced disease recurrence with 80% recurring within 2 years of resection. Treatment data for first-line palliative chemotherapy were available on 23 patients: 10 received platinum/etoposide and 13 received other regimens. In 19 patients with available imaging; the overall response rate was 52.6% (95% CI, 31.7-72.7) and there was no difference in ORR between platinum/etoposide (ORR=55.6%) or platinum plus other agents (paclitaxel or pemetrexed; ORR=55.6%). The median survival time was 26.3 months (95%CI; 18.6-33.9); the 1-, 2-, 3- and 5-year overall survival rates (OS) were 75%, 53%, 36%, and 30%, respectively. Patients who received platinum/etoposide demonstrated longer median time to progression (TTP), and median OS than those who received ‘other’ regimens (14.7 months vs. 7.1 months; p value 0.07, and 28.2 months vs. 21.1 months; p value 0.22, respectively); the differences did not reach conventional statistical significance, likely due to the small sample size. Rigorous pathologic confirmation and genomic analysis are ongoing.

      Conclusion:
      LCNEC is associated with a poor prognosis and high recurrence rates after surgery. Advanced LCNEC patients are at high risk for brain metastases, therefore, routine brain imaging surveillance during follow-up may be beneficial. The chemotherapeutic responsiveness of LCNEC patients was intermediate between that of NSCLC and SCLC patients. Future prospective, multicenter, clinical trials are needed to determine the best chemotherapy regimen for these rare tumors.

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      P1.07-037 - Clinicopathological Significance of Cancer Stem-Like Cell Markers in High-Grade Neuroendocrine Carcinoma of the Lung (ID 4993)

      14:30 - 15:45  |  Author(s): M. Morise, T. Hishida, A. Takahashi, J. Yoshida, Y. Ohe, K. Nagai, G. Ishii

      • Abstract

      Background:
      Over the past decade, cancer stem cells or cancer stem-like cells (CSLCs) have been identified in various tumors. However, few studies have examined the significance of CSLC marker expression in high-grade neuroendocrine carcinoma (HGNEC). This study aimed to evaluate the clinicopathological significance of CSLC markers in high-grade neuroendocrine carcinoma (HGNEC) of the lung, including small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC).

      Methods:
      We retrospectively studied patients who underwent surgical resection of SCLC (n = 60) and LCNEC (n = 45) to analyze their clinicopathological profiles and the immunohistochemical expression of putative CSLC markers (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1). Staining scores for these markers in tumor cells were calculated by multiplying the percentage of positive tumor cells per lesion by the staining intensity level (0, 1, and 2); a score of ≥ 10 represented positive expression.

      Results:
      There was a difference between SCLC and LCNEC with respect to both SOX2 (55 vs. 27 %, p = 0.003) and CD166 (27 vs. 47 %, p = 0.034) expression. ALDH1 expression was equally observed in SCLC and LCNEC (67 vs. 73 %, p = 0.46), and patients with ALDH1-positive HGNEC had significantly worse recurrence-free survival (RFS) and overall survival (OS) rates than those with ALDH1-negative HGNEC (5-year RFS: 39 vs. 67 %, p = 0.009; 5-year OS: 50 vs. 79 %, p = 0.021). A multivariate analysis revealed that positive ALDH1 expression was an independent unfavorable prognostic factor with respect to both RFS and OS.

      Conclusion:
      The differences in the expression profiles of CSLC markers might reflect morphological differences between SCLC and LCNEC. Positive ALDH1 expression in lung HGNEC was associated with an unfavorable patient prognosis, which suggested that ALDH1-positive tumor cells might be future therapeutic targets for the treatment of lung HGNEC.

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      P1.07-038 - Typical Morphological Features Revealed Unfavorable Survival Benefits in High-Grade Neuroendocrine Carcinomas (ID 5718)

      14:30 - 15:45  |  Author(s): H. Zhai, J. Zhang, L. Yan, C. Zhang, J. Su, S. Dong, Q. Nie, R. Liao, B. Jiang, X. Yang, Y.-. Wu, W. Zhong

      • Abstract
      • Slides

      Background:
      The 2015 WHO classification of lung cancer has proposed an revision about high-grade neuroendocrine carcinomas(HGNEC). Neuroendocrine(NE) markers are necessary for differentiations in cases lacing in typically morphological features, but their roles in survival benefits remain unclear.

      Methods:
      A total of 700 consecutive patients diagnosed with pNET were re-diagnosed during 2008 to 2015 and 632 were HGNECs. NE markers, such as Syn(synaptophysin), CgA(chromogranin A) and CD56, were stained by immunohistochemistry(IHC) if morphological features were not enough for diagnoses.

      Results:
      Four were excluded due to clinical identification of transformation from adenocarcinomas to SCLC. Nine HGNECs were previously diagnosed with AC. TTF1 stained 77.4%(459/593) HGNEC patients, of which 50.6% in LCNEC, 80.9% in SCLC and 62.5% in poorly differentiated HGNEC(P<0.001). Syn staining(94.1%, 571/607) were not statistically significant in three groups(89.1% vs. 94.6% vs. 100.0%, respectively; P=0.30). The same situation was in CgA(52.6%, 319/607), with a frequency of positive staining as 46.9%, 53.6% and 25.0%(P=0.26), respectively in three diagnoses. The number of positive NE markers were generally balanced(P=0.62). Cases with zero to three positive NE markers indicated marginal significant differences of overall survival(OS)(P=0.05). Meanwhile, no differences of mOS existed in positive and negative staining of Syn(14.7 vs. 32.53 mons, P=0.14) or CgA(14.6 vs. 15.9 mons, P=0.82); but patients with typical morphological features for diagnose and thus without IHC staining Syn or CgA (mOS, 9.13mons) bore significantly poorest OS benefits than those with positive(Syn, HR=2.71, 95%CI=1.24-5.86, P=0.01; CgA, HR=2.72, 95%CI=1.25-5.92, P=0.01) or negative(Syn, HR=3.44, 95%CI=1.39-8.52, P<0.01; CgA, HR=2.76, 95%CI=1.26-6.05, P=0.01) staining. The same condition occurred especially inⅠto Ⅲa patients(P<0.01). Figure 1



      Conclusion:
      The number of positive NE markers were necessary for precise diagnoses but not significant for survival benefits. Typical morphological features of NE tumor cells were unfavorable factors for OS. Further studies are imperative to identify its crucial role in HGNEC patients.

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      P1.07-039 - Insulinoma-Associated 1 (INSM1) Immunohistochemical Expression in Lung Neuroendocrine Tumors (ID 5407)

      14:30 - 15:45  |  Author(s): R. Sakakibara, K. Inamura, H. Ninomiya, Y. Shigematsu, T. Kakita, D. Noma, Y. Hirata, Y. Matsuura, M. Nakao, M. Mun, M. Nishio, S. Okumura, Y. Ishikawa

      • Abstract

      Background:
      Insulinoma-associated 1 (INSM1) is a transcription factor, and expressed during early embryonal development. In vitro and in vivo, INSM1 has been reported to regulate the neuroendocrine differentiation pathway represented by achaete-scute complex homolog-like1 (ASCL1) and neuroendocrine molecules (CGA, SYP, CD56) in lung cancer. We examined association between INSM1 protein expression and clinicopathological characteristics in lung neuroendocrine tumors.

      Methods:
      Using 139 consecutive surgically resected cases of lung neuroendocrine tumor (78 small cell lung carcinomas [SCLCs], 42 large cell neuroendocrine carcinomas [LCNECs], and 19 carcinoids), we evaluated INSM1 and ASCL1 immunohistochemical expression, and examined the association of INSM1 and ASCL1 expression with clinicopathological features.

      Results:
      For the 78 SCLCs, male/female ratio was 3.9:1, age ranged 46-84 with a median of 67 years, average cumulative smoking was 50.6 (pack-years), and 60/78 (77%) were positive for any one of neuroendocrine molecules. For the 42 LCNECs, male/female ratio was 5:1, age ranged 42-84 years with a median of 70, and average smoking was 47.9. For the 19 carcinoids, male/female ratio was 0.73:1, age ranged 38-85 years with a median of 67, and average smoking was 21.9. All of SCLCs positive for neuroendocrine molecules (n=60) were positive for INSM1 (60/60) and 72% positive for ASCL1 (43/60). In the SCLCs negative for all neuroendocrine molecules (n=18), 72% were positive for INSM1 (13/18) and all of them were negative for ASCL1 (0/18). For LCNECs, 57% were positive for INSM1 (24/42) and 50% were positive for ASCL1 (21/42). All of the carcinoids were positive for INSM1 (19/19) and 53% of them were positive for ASCL1 (10/19). Taken together, INSM1 and ASCL1 were detectable in lung neuroendocrine tumors by immunohistochemistry in 83% (116/139) and 53% (74/139), respectively.

      Conclusion:
      Our study suggests INSM1 is a sensitive and useful neuroendocrine marker, even for SCLC without apparent expression of neuroendocrine markers.

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      P1.07-040 - Prognostic Factors in Extensive Disease (ED) Small Cell Lung Cancer (SCLC): An ELCWP Phase III Randomised Trial (ID 4738)

      14:30 - 15:45  |  Author(s): T. Berghmans, J. Lafitte, A. Meert, A. Scherpereel, M. Paesmans, N. Leclercq, J. Sculier

      • Abstract
      • Slides

      Background:
      Main prognostic factors for survival in SCLC patients are performance status, disease extent, age or gender, as previously reported by the European Lung Cancer Working Party (ELCWP) (Paesmans et al, Eur Respir J 2011). Based on a previous meta-analysis (Mascaux et al, Lung Cancer 2000) showing a survival advantage for regimens including cisplatin (CDDP) or etoposide (VP16), the ELCWP designed a phase III trial to determine if addition of CDDP to VP16 would improve survival in comparison with VP16 combination without CDDP in a population of ED SCLC. The aim of this work was to search for prognostic factors for survival.

      Methods:
      Untreated patients with ED (limited (LD) not amenable to radiotherapy or stage IV disease) SCLC, Karnofsky performance status (PS) ≥60, adequate haematological, hepatic, renal and cardiac functions, were centrally randomised to receive either CDDP-VP16 (CE) or ifosfamide-VP16-epirubicin (IVE). According to statistical considerations, 315 deaths had to occur before analysis. Univariate and multivariate tests were performed for prognostic factors analyses.

      Results:
      346 eligible patients were randomised (176 in CE and 170 in IVE arms) between 2000 and 2013. At the time of analysis, 329 deaths occurred. No statistically significant imbalance was observed regarding age, gender, PS, disease extent (LD vs stage IV), neutrophil count and weight loss. No statistically significant difference was observed between CE and IVE groups according to main evaluation criteria: best response rate (60% vs 59%, p=0.88), progression-free survival (median 5.1 vs 5.3 months; p=1) and overall survival times with medians of 9.6 months and 10 months and 2-year rates of 5 % and 9 % (p=0.16), respectively. The following variables were statistically significantly associated with survival in univariate analysis: age (continuous evaluation) (HR=1.02, p=0.002), gender (male as reference) (HR=0.69, p=0.008), PS (PS ≤ 70 as reference) (HR=0.60, p=0.0001), weight loss (≤5% as reference) (HR=1.28, p=0.05) and neutrophil count (≤7500/mm3 as reference) (HR=1.46, p=0.003). In addition, variables with a p-value < 0.2 in univariate analysis were also included in the multivariate analysis: disease extent (LD as reference) (HR=1.38, p=0.10), WBC count (≤10000/mm3 as reference) (HR=1.23, p=0.08) and treatment arm (CE as reference) (HR=0.84, p=0.16). Two variables retained their statistical significance in multivariate analysis: gender (HR=0.69, 95% CI 049-0.97; p=0.03) and PS (HR=0.53, 95% CI 0.49-0.97; p<0.0001).

      Conclusion:
      Adding CDDP to VP16 failed improving survival in ED SCLC. In this population, gender and performance status confirmed their prognostic value for survival.

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      P1.07-041 - Validation of Prognostic Scores in Small Cell Lung Cancer (ID 6205)

      14:30 - 15:45  |  Author(s): R. Hagmann, A. Zippelius, S.I. Rothschild

      • Abstract
      • Slides

      Background:
      Treatment decisions in small-cell lung cancer (SCLC) are made based on the extent of the disease. However, the outcome differs among patients at the same stage. A simple tool to predict outcome in SCLC patients would be helpful for decision-making. In recent years, several prognostic scores have been proposed. However, most of them have never been validated in independent patient population.

      Methods:
      From January 2000 to December 2010, 92 SCLC patients were treated at our institution. Data acquisition from consecutive patients was done through patients’ medical records, and blood results recorded at the time of diagnosis. Univariate and multiple cox regression analyses of survival were performed to assess the prognostic value of relevant clinical and laboratory factors for SCLC. Furthermore, we investigated the relationship between seven published prognostic scores for SCLC and overall survival (OS).

      Results:
      We recently published clinical data of our study population (Hagmann R. J Cancer 2015). In a univariate analysis, we evaluated 29 parameters. Staging (p<0.001), number of metastastic sites (p<0.001), liver metastasis (p<0.001), bone metastasis (p<0.001), adrenal gland metastasis (p=0.028) and response to initial therapy (p<0.001) were significantly related to OS. From the established laboratory markers hypoalbuminemia (<35 g/l; p=0.044), hyponatraemia (<131 mmol/l; p=0.041), and elevated alkaline phosphatase (AP) (≥ 129 U/l; p<0.001) significantly predicted OS. Multivariate analysis confirmed staging (HR 2.7; p=0.022) and elevated AP (HR 3.3; p=0.004) as independent prognostic factors. The Manchester Score incorporating LDH, tumor stage, serum sodium, Karnofsky performance status, AP and serum bicarbonate (Cerny T. Int J Cancer 1987) was the only published scoring system significantly associated with OS. Patients in good, intermediate and poor prognosis groups had a median OS of 12.9, 6.6 and 5.8 months, respectively (p=0.008).

      Conclusion:
      We confirmed the prognostic role of the Manchester Score in an independent patient population whereas the reliability of more complex and recent scoring systems could not be validated. We therefore recommend using simple clinical and laboratory factors instead of complex scores to estimate prognosis of SCLC patients.

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      P1.07-042 - Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Predict Prognosis in Early-Stage Resected Small-Cell Lung Cancer Patients (ID 5657)

      14:30 - 15:45  |  Author(s): V. Hollosi, J. Moldvay, M. Bendek, G. Ostoros, B. Hegedus, B. Dome, G.J. Weiss, Z. Lohinai

      • Abstract
      • Slides

      Background:
      Surgical resection is rarely possible in small-cell lung cancer (SCLC), a highly aggressive malignancy with limited treatment options. However, although in the past decades, for selected early-stage cases, a curative intent surgery is often performed, there is no biomarker to help the selection of patients eligible for surgery. Because previous studies - predominantly from East Asia - showed that high neutrophil to lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) correlate with poor prognosis in several types of tumors including SCLC, the aim of our study was to investigate the prognostic value of NLR and PLR in Caucasian patients with resected SCLC.

      Methods:
      Consecutive patients with histologically confirmed and surgically resected SCLC evaluated between 2000 and 2013 at the National Koranyi Institute of Pulmonology were analyzed in this retrospective analysis. Patients were divided into "high" and "low" groups according to their NLR and PLR at diagnosis. The cut-off NLR and PLR values were 3 and 110, respectively. Next, we evaluated the associations of preoperative NLR or PLR with vascular involvement, tumor necrosis, peritumoral inflammation, tumor grade, clinicopathological characteristics (including age, gender, stage) and overall survival (OS) in univariate and multivariate analyses.

      Results:
      There were a total of 65 patients (39 men and 26 women) with a median age of 57.7 years (range, 40-79). The pathological stages were 1, 2 and 3A in 23, 23 and 14 cases by AJCC 7[th] edition (in five patients no pTNM was available). PLR was high (HPLR) in 41 (63%) and low (LPNR) in 24 (37%) patients. NLR was high (HNLR) in 35 (66%) and low (LLNR) in 17 (33%) patients. PLR significantly correlated with pathologic lymph node status (p<0.001) and NLR (p=0.007). HPLR was associated with shorter OS (vs. LPLR, HR, 2.2; 95% CI, 1.13–4.29; p=0.02). There was a non-significant trend towards longer OS in patients with LNLR (vs. HNLR, p=0.078). There were no significant associations between NLR or PLR and age, gender, stage, vascular involvement, tumor necrosis, peritumoral inflammation and tumor grade.

      Conclusion:
      This is the first study in Caucasian patients with resected SCLC which shows that LPLR (<110) before surgical resection may be a favorable prognostic factor for longer OS. We also conclude that preoperative HPLR may predict lymph node involvement. PLR but not NLR may help in selecting patients for surgery in the future. Further prospective studies are needed to confirm these observations.

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      P1.07-043 - Patterns of Failure and the Prognostic Factors of the Patients with LD SCLC according to the TNM Staging; TOG-TROD Study   (ID 6100)

      14:30 - 15:45  |  Author(s): Ş.A. Ergen, H.F. Dinçbaş, E. Metcalfe, S. Akyurek, G. Yavaş, Ş. Ülger, B.Ş. Özdemir, B. Yücel, D.Ç. Öksüz, M. Şenocak, H. Bozcuk

      • Abstract
      • Slides

      Background:
      The prognostic factors and patterns of relapse were retrospectively analyzed according to the TNM staging in Turkish patients with limited SCLC on behalf of Turkish Oncology Group(TOG)-Turkish Radiation Oncology Association(TROD).

      Methods:
      The data of 266 patients with limited disease SCLC from 13 multiple oncology centers who have at least 1 year follow-up were analyzed. The patients were restaged according to TNM staging by means of their initial thorax-CT or PET-CT . Brain MRI was performed for all of the patients before treatment. Median age was 59(21-86) years old and 85% of the patients were male. PET-CT was used in 62.4 % of the patients for staging. Concomitant chemoradiotherapy with Cisplatinum-Etoposide was given in 38.3% of the patients. Median thoracic radiotherapy dose was 56Gy(30-66.8Gy). PCI was performed to the 180 patients (67.7%) , The effect of age, gender,clinical stage, T, N stage and prophylactic cranial irradiation(PCI) on OS and DFS rates were analyzed in both univariate and multivariate analysis with Log-rank and cox regression tests.

      Results:
      Median follow-up was 19 months(6-113 ) for the patients who are alive. Thirty-six percent of the patients had LR and approximately half of the patients developed DM. The most common metastases were seen in brain, liver and bone respectively. 2 and 5 years OS and DFS were 45.3%-20.6% and 32.2%-17.1% retrospectively. On univariate analysis, OS was significantly better in the patients with T1, N0-1 tumors and clinical stage I-II than the others and patients who did not developed brain and DM and thoracic radiotherapy dose >60Gy(p<0.05). DFS was superior in patients with N0-1 tumor, stage I-II disease, who received PCI and thoracic radiotherapy dose >60Gy(p<0.05). On multivariate analysis, PCI was found to be an independent factor affecting DFS (p=0.042). DM, thoracic radiotherapy dose were significant prognostic factors for OS (p=0.048, <0.0001 respectively). 64 patients developed brain metastases with a median 16 months(6-113months). Brain metastases were find to be significantly less in the patients with N0 , stage I-II disease and who were treated by PCI.

      Conclusion:
      Limited disease definition includes wide spectrum of patients, therefore TNM staging should be useful in order to predict the prognosis of the patients. In our series, DFS and OS was superior for the patients with T1 and N0-NI tumors than the others . Besides, the patients with T1 and N0 tumors developed fewer brain metastases, therefore PCI might be omitted for some of the patients with early staged tumor.

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      P1.07-044 - Educational Level and Management in Small-Cell Lung Cancer (SCLC): A Population-Based Study (ID 4568)

      14:30 - 15:45  |  Author(s): S. Tendler, M. Holmqvist, G. Wagenius, R. Lewensohn, K. Viktorsson, L. De Petris

      • Abstract
      • Slides

      Background:
      In a previous study we reported that educational level is a prognostic factor in SCLC, with females and LD patients with a higher education having a longer survival. In this study we examined possible associations between educational level, lead times and treatment strategies in the same cohort.

      Methods:
      The study was based on information in LcBaSe, a lung cancer research database generated by record linkages between the Swedish National Lung Cancer Register and several other population-based registers. Educational level was categorized according to number of years of schooling;low(≤ 9 years), middle (10-12 years), high (≥13 years). Stage was classified as limited disease (LD) and extensive disease (ED). Lead times were defined as A) from first radiological sign of a tumor to definite diagnosis and B) from date of referral from primary care to diagnosis. Treatment groups were divided as; chemotherapy (CT), CT+Radiation Therapy (CT+RT), Palliative RT or no oncological therapy.

      Results:
      The study population encompassed 4278 patients with a SCLC diagnosis between 2002-2011. Median age was 69 years. 988 (23.1 %) patients were diagnosed with LD (low E: 22.9 %, middle E: 23.6%, high E: 26.7 %) and 3187 (74.5 %) with ED (low E: 74.8, middle E: 74.0 %, high E: 73.3%) .One fifth of patients had a poor performance score (PS 3-4). The median lead time A was 14 days (IQR 5-32 days) and for lead time B 9 days (IQR 3-21 days). There were no differences in lead times between the educational groups. The proportion of patients receiving CT+RT was approximately 80 % in LD (Low E: 78.5% Middle E: 79.2% High E: 82.4 %) and 5 % in ED (Low E: 4.2%, Middle E: 5.3% High E: 6.8%). The percentage of patients receiving CT was 18 % in LD (Low E: 19.7% Middle E: 18.7 % High E: 15.3%) and 82 % in ED (Low E: 81.2 %, Middle E: 83.9 % High E: 81.4 %).

      Conclusion:
      There were no significant differences between educational groups in lead times or management. We conclude that the prognostic impact of educational status in Swedish SCLC patients does not appear to reflect inequalities in access to the healthcare.

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      P1.07-045 - Characteristics of Exceptional Long Term Survivors in Extensive Stage Small Cell Lung Cancer (ID 5527)

      14:30 - 15:45  |  Author(s): K. Maneenil, J. Molina, J. She, R. Gupta, M.C. Aubry, E.S. Yi, P. Yang

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) remains a frustrating disease to all parties involved. Most patients present with extensive stage disease (ED), with a median survival of 8 to 13 months (Expected). The aim of this study is to present data on survivors who lived beyond 3 years after a diagnosis of ED-SCLC (Exceptional) in order to uncover favorable factors for better patient management and clinical outcomes.

      Methods:
      We retrospectively evaluated the SCLC patient cohort diagnosed and followed from 1997 to 2015 at Mayo Clinic (Minnesota), and searched for Exceptional survivors with matched Expected survivors who had passed away within 12 months of diagnosis on age and year of diagnosis. Patient characteristics, treatments, and outcomes were compared between the two groups.

      Results:
      To date, we identified 36 Exceptional and 144 Expected ED-SCLC patients. Women and an Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) 0-1 were higher in Exceptional than in Expected group (61.8% vs 36.1%, p<0.01; 97.2% vs 77.6%, p<0.01; respectively). Smoking history, comorbidities (COPD, prior cancers or paraneoplastic syndrome), and T or N stage did not differ significantly. The top two metastatic sites in Exceptional group were brain (26.7%) and distant lymph nodes (20.0%), and in Expected were liver (28.3%) and bone (22.5%). Use of chemotherapy and the mean cycle number were higher in the Exceptional than the Expected group (100.0% vs 80.0%, p<0.01; 5.0 vs 3.6, p<0.01; respectively), with the main regimen being platinum/etoposide. However, carboplatin was used more frequently than cisplatin in Expected group (all patients, p=0.02; ECOG 0-1 patients, p=0.05). The overall response rate of chemotherapy was significantly higher in exceptional group (91.4% vs 56.7%, p<0.01). Thoracic radiotherapy and prophylactic cranial irradiation (PCI) in Exceptional were also higher than in Expected group (58.3% vs 17.4%; p<0.01, 19.4% vs 6.9%; p=0.03). Multivariate analysis is underway. In Exceptional group, median overall survival was 5.4 years (95% CI 3.7-6.8); 9 (25%) patients were still alive. Twelve (33%) patients had disease recurrence or progression with the median progression free survival 1.2 (95% CI 0.7-2.0) years. The most common recurrent site was brain. Three patients had secondary malignancy, 2 being a non-small cell lung cancer.

      Conclusion:
      Although the chance of curing ED-SCLC is small, long-term survival can be achieved. This study supports the importance of good performance status and the achievement of a response to cisplatin-based chemotherapy on long-term survival. Addition of thoracic radiotherapy and PCI are beneficial in prolong life of ED-SCLC patients.

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      P1.07-046 - Uptake of Recommended Treatment in Small Cell Lung Cancer: Trend over the Last 15 Years and Risk Factors (ID 6326)

      14:30 - 15:45  |  Author(s): T. Anggondowati, K.M. Islam, A.K. Ganti

      • Abstract

      Background:
      Despite the dismal outcomes of small-cell lung cancer (SCLC), the fact that SCLC patients are generally responsive to treatment emphasizes the importance of adherence to recommended treatment. This study analyzed the trend in treatment provision in SCLC over the last 15 years and its associated factors.

      Methods:
      A total of 207,375 adult patients diagnosed with SCLC between 1998 and 2012 in the United States were identified from the National Cancer Data Base. In this study, recommended treatment was defined as surgery and/or chemoradiation for the limited stage (LS-SCLC), regardless of sequence; and chemotherapy for the extensive stage (ES-SCLC). We excluded patients who did not receive treatment due to a contraindication. Logistic regression was used to analyze the risk of not receiving recommended treatment, adjusted for socio-demographics, facility type, and clinical factors. Kaplan-Meier estimator was used to estimate patients’ survival.

      Results:
      Between 1998 and 2012, the proportion of patients receiving recommended treatment increased among LS-SCLC patients (63% to 73.4%), but was unchanged in ES-SCLC (75.7% to 76.6%). Nevertheless, a significant proportion of patients did not receive recommended treatments. Older age, low income, use of non-private insurance or no insurance, higher comorbidity score, and diagnosis and/or treatment at a community cancer program were independent predictors of inadequate treatment for both LS-SCLC and ES-SCLC, while Black race was a predictor only in LS-SCLC. For instance, compared to patients with private insurance, the odd ratios of uninsured patients not receiving recommended treatment or no treatment was 1.7 (95% CI 1.543-1.932) in LS-SCLC and 1.9 (95% CI 1.751-2.060) in ES-SCLC patients. Both LS-SCLC and ES-SCLC patients aged 65-74 years had 1.5 (95% CI for LS-SCLC: 1.402-1.587; 95% CI for ES-SCLC: 1.454-1.613) times higher odds of not receiving recommended treatment or no treatment, compared to younger patients. In both groups, patients who received recommended treatment had better survival than those who did not receive recommended treatment or any treatment (median survival time of 18.4 vs. 6 months in LS-SCLC; 8.3 vs. 1.2 months in ES-SCLC).

      Conclusion:
      This study demonstrated an increase in the uptake of recommended treatment in LS-SCLC, but relatively no change in ES-SCLC. Reasons for not receiving recommended treatment warrant further investigation. The survival benefit among patients with recommended treatment highlights the need to alleviate any system-based barriers that may impact more patients receiving recommended treatment.

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      P1.07-047 - Refusal of Chemoradiotherapy and Chemotherapy among SCLC Patients: Analysis of US National Facility-Based Data (ID 5360)

      14:30 - 15:45  |  Author(s): P.E. Deviany, K.M. Islam, A.K. Ganti

      • Abstract

      Background:
      Less than 7% of small cell lung cancer (SCLC) patients survive five years after diagnosis. Although receipt of recommended treatment is a key to survival, factors associated with treatment refusal have not been well studied in SCLC. Our study examined factors associated with treatment refusal by SCLC patients and effect of refusal on survival.

      Methods:
      We analyzed data of 114,004 SCLC patients diagnosed between 2003 and 2012 from the National Cancer Data Base. Analyses were conducted separately for refusal of chemoradiotherapy among limited stage (LS) and refusal of chemotherapy among extensive stage (ES) patients. We used multivariable logistic regression to investigate factors associated with treatment refusal and calculated median survival using Kaplan-Meier method.

      Results:
      There was a female preponderance among LS (56%), whereas 52% of ES patients were male (p <.001). Majority of the LS patients received chemoradiotherapy (67%), and ES patients received chemotherapy only (44%) as their first-course treatment. Refusal of chemoradiotherapy among LS patients was 2%, and refusal of chemotherapy among ES patients was 5%. On multivariable analysis, patient diagnosed at age >70 years were more likely to refuse treatment compared to those age 50-70 years; the adjusted odds ratio (AOR) was 3.39 (95% CI: 2.68-4.28) for refusal of chemoradiotherapy among LS patients and 2.54 (95% CI: 2.28-2.84) for refusal of chemotherapy among ES patients. Females were more likely to refuse recommended treatment than males, the AOR was 1.34 (95% CI: 1.09-1.65) for refusal of chemoradiotherapy and 1.29 (95% CI: 1.17-1.42) for refusal of chemotherapy. Compared to those with private insurance, uninsured patients were more likely to refuse chemoradiotherapy (AOR= 2.70, 95% CI: 1.49-4.91) and chemotherapy (AOR=2.26, 95% CI: 1.76-2.91). Patients with comorbid conditions were more likely to refuse recommended treatment compared to those without comorbidity; the AOR was 1.66 (95% CI: 1.33-2.07) for refusal of chemoradiotherapy and 1.37 (95% CI: 1.23-1.53) for refusal of chemotherapy. Median survival of LS patients who received and refused chemoradiotherapy was 18 and 3 months respectively (p <.001). Among ES patients, median survival was 8 months for those who received chemotherapy and 1 month for those who refused (p <.001).

      Conclusion:
      Although treatment refusal was uncommon, older age at diagnosis, female, uninsured status, and comorbid conditions were associated with higher treatment refusal. These factors should be specially addressed in patient-provider communication and patient-education. Interventions targeting these issues will increase acceptance of recommended treatment and ultimately will improve patient outcomes.

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      P1.07-048 - Clinical Impact of the Relationship between Post-Progression Survival and Overall Survival in Extensive Disease Small Cell Lung Cancer Patients (ID 4303)

      14:30 - 15:45  |  Author(s): H. Imai, K. Mori, N. Watase, S. Fujimoto, K. Kaira, M. Yamada, K. Minato

      • Abstract

      Background:
      The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small-cell lung cancer (SCLC). Therefore, by using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) or post-progression survival (PPS) and OS after first-line chemotherapies in patients with extensive disease SCLC (ED-SCLC) treated with carboplatin plus etoposide.

      Methods:
      Between July 1998 and December 2014, we analyzed 63 cases of patients with ED-SCLC who were treated with carboplatin and etoposide as first-line chemotherapy. The relationships of PFS and PPS with OS were analyzed at the individual level.

      Results:
      Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.90, p < 0.05, R[2 ]= 0.71) and PFS was moderately correlated with OS (r = 0.72, p < 0.05, R[2] = 0.62). Type of relapse (refractory/sensitive) and the number of regimens administered after disease progression after the first-line chemotherapy were both significantly associated with PPS (p < 0.05).

      Conclusion:
      PPS has a stronger relationship with OS than does PFS in ED-SCLC patients who have received first-line chemotherapy. In addition, type of relapse (refractory/sensitive) after first-line treatment and the number of additional regimens after first-line treatment are significant independent prognostic factors for PPS. These results suggest that treatments administered after first-line chemotherapy affect the OS of ED-SCLC patients treated with carboplatin plus etoposide.

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      P1.07-049 - Limited Stage Small Cell Lung Cancer: Patterns of Care and Outcomes of a Single Institution over 15 Years (ID 4416)

      14:30 - 15:45  |  Author(s): E. Hwang, J. Williams, R. Venchiarutti, C. Lewis, W. Wong

      • Abstract
      • Slides

      Background:
      The past two decades have seen an increase in survival of patients with limited stage small cell lung cancer (SCLC). This retrospective audit analysed patterns of care, toxicity and survival for all patients with limited stage SCLC diagnosed and treated at Prince of Wales hospital over 15 years. Our results were compared with the literature to assess this single institution’s performance and outcomes, and explore what factors may most be influencing these results.

      Methods:
      We identified 120 patients diagnosed with SCLC at Prince of Wales Hospital between 2000 and 2014 from the departmental electronic patient information system (Mosaiq). Eligibility criteria were: age >18 years, histopathologically confirmed diagnosis of SCLC, limited stage according to the two-stage Veterans’ Affairs Lung Study Group staging criteria (2016), and treatment with either curative or palliative intent. Median progression free survival (PFS), cancer specific survival (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test (IBM SPSS version 23.0).

      Results:
      Thirty-two patients fulfilled the eligibility criteria. The median age of patients was 66.5 years; 19 (59%) patients were female and 50% had an Eastern Cooperative Oncology Group (ECOG) score of 0. Median PFS, CSS and OS were 12.6, 22.1 and 18.0 months respectively, comparable with published literature. Ten patients (31%) received prophylactic cranial irradiation (PCI) as a component of their therapy. Of the 10 patients who received PCI, none had brain recurrence, while 36.4% of the non-PCI group developed brain metastases. Patients receiving PCI demonstrated a trend toward improved PFS compared to patients not receiving PCI (18.3 months versus 10.5 months, p=0.057). This trend was also seen in OS in this group (25.4 months versus 15.5 months, p=0.072). The median time from date of diagnosis to start of chemotherapy was 21 days, and there was correlation between time to chemotherapy and OS (p=0.037) and PFS (p=0.045). Twenty-six of the 32 patients underwent a combination of chemotherapy and radiotherapy. Seventeen patients (65%) received concurrent chemoradiotherapy, and 9 (35%) received sequential chemoradiotherapy, with no significant difference in survival or toxicity between these two regimens.

      Conclusion:
      Survival outcomes from this single institution are comparable with current literature. The use of PCI in appropriate patients can prevent cerebral metastases, improve PFS and ultimately OS. The time to initiation of chemotherapy may also have a significant impact on outcomes.

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      P1.07-050 - Patterns of Relapse in Small Cell Lung Cancer (SCLC): A Retrospective Analysis of Outcomes from a Single Canadian Center (ID 5387)

      14:30 - 15:45  |  Author(s): A.M. Al Farsi, A. Swaminath, P.M. Ellis

      • Abstract
      • Slides

      Background:
      We conducted a retrospective review of small cell lung cancer patients (SCLC) to explore patterns of relapse and utility of Prophylactic Cranial Irradiation (PCI).

      Methods:
      A retrospective chart review was carried on patients diagnosed with SCLC from January 1[st] 2011 until December 31[st] 2014 and treated at Juravinski Cancer Center. The primary outcome was to determine pattern of first relapse. Secondary outcomes were physician assessed response rate, overall survival (OS), utilization of PCI, time to systemic relapse (TTR) and time to central nervous system (CNS) relapse.

      Results:
      A total of 275 patients were identified, of whom 46 (16.7%) received no chemotherapy (median OS 2.2 months (m)) and were not included in further analyses. The median age of 229 treated patients was 66 (SD 9.3) yrs. There were 115 men, 114 women, 84 (37%) had limited stage (LS) and 145 (63%) extensive stage (ES) disease, performance status (PS) was 0-1 in 133 (58%), PS2 in 66 (28%) and PS3-4 in 32 (13%). Brain metastases were present in 36 (16%) patients at diagnosis. Almost all patients received cisplatin (53%) or carboplatin (43%) plus etoposide chemotherapy. Most patients received 4 (23%), or more (52%) cycles of chemotherapy. Physician assessed RR was 68% (PR 61%, CR 7%) and 16% of patients progressed during first-line therapy. Thoracic radiation (TRT) was given to 112 (49%) of patients (LS 87%, ES 27%). Patients with brain metastases at diagnosis, or progressing during first-line chemotherapy were not considered eligible for PCI. Among 156 eligible patients, 80 (51%) received PCI (LS 64%, ES 39%). Forty-one patients (26.3%) declined PCI. The median overall survival for all patients was 11.1m (LS 21.7m, ES 8.9m). Relapse occurred in 167 (73%) of patients: CNS alone 8.7%, CNS plus systemic relapse (13.1%), thoracic (28%), extra-thoracic (9%), thoracic/extra-thoracic (14%). Median time to any relapse was 9.2m (LS 14.3m, ES 7.5m), while median time to CNS relapse was 6.9m (PCI given 6.2m, PCI not given 4.4m). Among 50 patients with CNS relapse, 16 received PCI (LS 9, ES 7) and 34 did not (LS 8, ES 26). Among 64 patients with thoracic relapse, 31 received TRT (LS 19, ES 12) and 33 did not (LS 5, ES 28).

      Conclusion:
      Only 50% of eligible SCLC patients receive PCI. CNS relapse occurs frequently and more commonly in patients who do not receive PCI. Implementation of PCI in routine clinical practice appears to influence patterns of recurrence.

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      P1.07-051 - Incidence and Clinical Characteristics of Pulmonary Large-Cell Neuroendocrine Carcinoma: An Overview of Our Own Data (ID 6188)

      14:30 - 15:45  |  Author(s): G. Drpa, K. Krasnic, M. Serdarevic, F. Popovic, B. Budimir, S. Kukulj

      • Abstract
      • Slides

      Background:
      Pulmonary neuroendocrine tumors are a heterogenous group of neoplasms. They are clasified into four histological types: typical carcinoid, atypical carcinoid, small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). They represent about 20% of all lung cancers. The most frequent one is small-cell lung cancer with incidence about 15%. In contrast, large-cell neuroendocrine carcinoma is an orphan disease with estimated incidence between 2.1% and 3.5%. Because of many diagnostic difficulties, LCNEC is considered to be of a higher frequency. It is lung neuroendocrine tumor, but it is also a type of non small-cell lung cancer (NSCLC). So its features overlap with both of these groups. However, the clinical behavior of LCNEC is very similar to SCLC and so new term high-grade neuroendocrine carcinoma (HGNEC) is in use.

      Methods:
      We retrospectively analysed patients diagnosed with cancer at our department between January 1, 2012 and December 31, 2014, with special focus on pulmonary neuroendocrine tumors. We examined incidence of different histologic types of pulmonary neuroendocrine tumors and sorted out patients with diagnosis of large-cell neuroendocrine carcinoma. We also analysed clinical characteristics of patients with LCNEC.

      Results:
      During the three-years period 1242 pulmonary patients were admitted to our department. Among them there were 726 newely diagnosed cancer patients. Various types of lung cancer were found in 652 patients. There were 104 patients with pulmonary neuroendocrine tumors, what makes about 16%. Thirteen of them (2%) were „pure“ LCNEC , 16 (2,5%) mixed LCNEC with small-cell component, 68 SCLC (10%), 4 atypical carcinoid, 2 typical carcinoid and 1 typical carcinoid in patient with adenocarcinoma. Generally in our patients high-grade neuroendocrine tumors make about 15%, and low-grade neuroendocrine tumors (carcinoides) make only 1% of all lung cancers. Most patients diagnosed with LCNEC were men over 50 years, heavy smokers, which is consistent with published data, but one patient was a 40-year-old woman.

      Conclusion:
      Pulmonary neuroendocrine tumors are group of neoplasms classified into four categories based on their patohistology. Three of them (carcinoides and LCNEC) are rare tumors. LCNEC is type of neuroendocrine tumor with most diagnostic and therapeutic difficulties. Clinical features of our patients are similar to previously published, while incidence is slightly lower.

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      P1.07-052 - Pulmonary Neuroendocrine Tumors: Single Institution Experience in Brazil (ID 5816)

      14:30 - 15:45  |  Author(s): R.M. Rosenthal, M.T.R. Tsukazan, Á. Vigo, F.D. Cabral, A. Vieira, G.M. Schwarcke, J. Rios, J.A.L.F. Pinto, V. Duval Da Silva

      • Abstract

      Background:
      The primary lung neuroendocrine tumors (NET) are uncommon. They have a wide spectrum of clinical behavior, currently being classified into four types: tumor typical carcinoid (low grade malignancy), atypical carcinoid (intermediate malignancy grade), neuroendocrine large cells carcinoma and small cells. Neuroendocrine lung tumors represent a large and heterogenic group with different management and survival rates. Little information regarding neuroendocrine tumors is available for Latin American countries.

      Methods:
      Retrospective service database review of patients with NET treated at Hospital São Lucas in Porto Alegre, Brazil between 1991-2015. Inclusion criteria were age 18 or older with histologically or immunochemistry confirmed neuroendocrine tumor. For analysis purposes we divided between, typical carcinoid, atypical carcinoid and poorly differentiated (large and small cells).

      Results:
      From January of 1991 to December of 2015, of 946 lung cancer resections 49 patients with NET were resected. Most the patients were female (57,1%), mean age 55 years (28- 84 years). Typical carcinoid represented 63,3% of patients, followed by atypical carcinoid (22,4%) and poorly differentiated neuroendocrine tumors (14,3%). Mean age was 51,4 for typical carcinoid, 56 for atypical carcinoid and 63 for undifferentiated NET. Lobectomy was the surgical approach for 85,7%,, pneumonectomy was required for 4,1% and segmentectomy for 10,2% of patients. Minimally invasive (VATS) was done in 4,1%. Figure 1



      Conclusion:
      According to the European Consensus, pulmonary carcinoids account for 1–2% of all invasive lung malignancies. We found 85,7% of our lung resections were carcinoids and a higher mean age 51,4 for patients with typical and 56 for atypical carcinoids compared to the literature.

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      P1.07-053 - Apatinib for Chemotherapy-Refractory Extensive Stage SCLC: Results from a Single-Center Retrospective Study (ID 6417)

      14:30 - 15:45  |  Author(s): W. Hong, H. Li, X. Jin, X. Shi

      • Abstract

      Background:
      It has no standard treatment strategy for patients with extensive stage small cell lung cancer (SCLC) who experienced progression with three or more lines of chemotherapy. Apatinib, a new tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), has been shown confirming antitumor activity and manageable toxicities in breast and gastric cancers. Until now, couples of clinical trials investigating the efficacy of apatinib on non-small cell lung cancer are ongoing. However, the effects of apatinib on small cell lung cancer are still unclear. We retrospectively assessed the efficacy and safety of apatinib in patients with extensive-stage small cell lung cancers after the failure of second or third-line chemotherapy.

      Methods:
      The study group comprised 13 patients who received oral apatinib, at a dose of 500 mg daily, for progression after the failure of second or third-line chemotherapy for extensive-stage small cell lung cancer. Treatment was continued until disease progression. For the patients who had grade 3 or 4 toxicities, the dose of apatinib was decreased to 250mg daily. The patients stopped the treatment if they still had the unacceptable toxicity after dose downregulation. We analyzed safety and response (RECIST 1.1) for the available patients monthly.

      Results:
      Between Aug 30, 2015 and May 1, 2016, 13 patients were enrolled. In 13 patients, there were 11 patients available for efficacy and safety evaluation. 5/11 (45.5%) patients experienced dose reduction during treatment. Followed up to July 20, 2016, the median during time of afatinib treatment was 2.8 months (95% confidence interval (CI), 1.67-5.04). According to RECIST criteria, the disease control rate was 81.8%, 9/11 (partial response 18.2%, 2/11 and stable disease 63.6%, 7/11). The most frequent treatment-related adverse events were secondary hypertension (45.5%, 5/11), oral mucositis (27.3%, 3/11), hand-foot syndrome (27.3%, 3/11) and fatigue (27.3%, 3/11). Main grade 3 or 4 toxicities were hypertension (27.3%, 3/11), oral mucositis (9.1%, 1/11) and fatigue (9.1%, 1/11).

      Conclusion:
      Apatinib exhibits modest activity and acceptable toxicity for the heavily pretreated patients with extensive-stage small cell lung cancer.

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      P1.07-054 - Second Primary Small Cell Carcinoma of Lung in Previously Treated Carcinoma Breast (ID 6385)

      14:30 - 15:45  |  Author(s): P.R. Mohapatra, P. Mishra, M.K. Panigrahi, G. Pradhan, S. Bhuniya, S. Patra, M. Kar

      • Abstract

      Background:
      Breast cancer is the major cause of cancer among women worldwide. Some of the patients are treated with surgery followed by adjuvant chemotherapy and radiation therapy. It is presumed that the radiation of surrounding tissues during breast radiotherapy may cause cancer in other areas of body.

      Methods:
      A 40 year old woman presented with chest pain and breathing difficulties for four months. She was diagnosed as infiltrating duct cell carcinoma of right breast and undergone modified radical mastectomy. Her 1 of 20 lymph nodes showed tumour metastases with perinodal extension. Triple marker (oestrogen receptor, progesterone receptor, her 2 neu receptor) was negative. She was given four cycles of CEF regimen cyclophosphamide,epirubicin,5-FU) and four cycles of paclitaxel. She had also received 25 fraction of radiotherapy completed over one year before. There was no other co-morbid conditions, family history was not significant. She had average body built and nutrition. On general examination mild pallor was only positive finding, no peripheral lymphadenopathy or clubbing. Contrast enhanced computed tomogram of chest revealed bilateral lung nodular infiltrates more predominantly in left lower lobe, mediastinal lymphadenopathy with left lower lobe collapse. Ultrasound abdomen detected no significant abnormality. Bronchoscopy showed multiple nodules present over carina, infiltration in right lower lobe segmental opening, left main bronchus lumen narrowed due to diffuse infiltrative growth. The endobrochial biopsies were taken from this area.

      Results:
      Endobronchial biopsy revealed tumour cells were strongly and diffusely positive for synaptophysin and negative for chromogranin and TTF1 . The diagnosis of small cell carcinoma lung was made. MRI of brain showed ring enhancing lesions in right cerebellar hemisphere suggestive of metastases. Staging of the tumour came to T4N2M1a according to 8th edition of IASLC TNM classification for lung cancer. Her performance status improved to ECOG 2. She was given cisplatin and etoposide in addition to brain radiation therapy.

      Conclusion:
      The second primary malignancy refers to a different type of cancer in a person who has survived an earlier cancer. There are series of non- small cell lung cancer (NSCLC) reported as second primary after breast cancer. To our knowledge, this is the first case presented as small cell lung cancer as second malignancies in lung in a fully treated breast cancer patient. This may be related risk of second malignancies associated with radiotherapy exposure to lung applied for breast cancer or due to adjuvant treatment as in this case.

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      P1.07-055 - Introducing the US National Cancer Institute’s Small Cell Lung Cancer Consortium (ID 6065)

      14:30 - 15:45  |  Author(s): P. Ujhazy, E. Szabo, S. Forry

      • Abstract
      • Slides

      Background:
      Small cell lung cancer (SCLC) remains a major clinical challenge, however recent discoveries and early positive signals in clinical trials are promising more optimistic outcomes for patients with this disease. The United States National Cancer Institute (NCI) launched in December 2015 a series of solicitations for grant applications with the goal to establish a SCLC consortium. The Consortium will address five strategic priority areas established by an international group of experts and the NCI. These areas are: 1. Better research tools for the Study of SCLC, 2. Comprehensive genomic profiling of SCLC, 3. New diagnostic and prevention approaches for SCLC, 4. Therapeutic development efforts, and 5. Mechanisms underlying both high rate of initial response and rapid emergence of drug and radiation resistance. The initiative for early detection and prevention of SCLC is now open for potential applicants through 2017 (PAR-16-51); applications for therapy and mechanism of resistance projects can be submitted through 2018 (PAR-16-49).

      Methods:
      Section not applicable

      Results:
      (Note: The first round of application was reviewed right before the IASLC abstract submission deadline, funding decisions will be made in early November 2016, so by the time of the November 11 deadline for the poster submission we will be able to include the first funded projects in the consortium in the abstract and in the poster.)

      Conclusion:
      Section not applicable

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    P1.08 - Poster Session with Presenters Present (ID 460)

    • Type: Poster Presenters Present
    • Track: Surgery
    • Presentations: 84
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      P1.08-001 - Log Odds as a Novel Prognostic Indicator Superior to the Number-Based and Ratio-Based Category for Non-Small Cell Lung Cancer (ID 3913)

      14:30 - 15:45  |  Author(s): D.A. Dziedzic, P. Rudzinski, T. Orlowski

      • Abstract
      • Slides

      Background:
      The paper aimed to compare the efficacy of log odds (LODDS) compared to a classification based on the number of positive lymph nodes (pN) and lymph node ratio (LNR).

      Methods:
      Material was collected retrospectively from an online survey-based database of the Polish Lung Cancer Group and included a group of 17369 patients who received radical surgical treatment (R0) due to lung cancer. The follow-up period was between 11.4 and 66.0 months (median 30.1 months).

      Results:
      In the whole group the median survival for N0, N1 and N2 was 76.1, 41.7 and 24.2 months, respectively. The median survival for individual LODDS categories (-6,-4], (-4,-3], (-3,-2], (-2,-1], (-1,0], (0,1] and (1,2] was 76.5, 76.3, 71.7, 45.4, 25.0, 19.1 and 17.7 months, respectively. The median survival for LNR in individual categories (0), (0,0.25], (0.25,05], (0.5,075] and (0.75,1.0] was 75.6, 40.3, 24.1, 18.8 and 16.4 months, respectively. When comparing LODDS and LNR significant heterogeneity can be seen that is especially visible in categories (0), (0,0.25] LNR, where 4 LODDS categories were distinguished. A multi-variant analysis demonstrated that each LODDS category is an independent prognostic factor: (-4,-3] (HR = 0.982; 95% CI 0.867-1.112; P = 0.775), (-3,-2] (HR = 1.114; 95% CI 0.984-1.262; P = 0.089), (-2,-1] (HR = 1.241; 95% CI 1.080-1.425; P = 0.002), (-1,0] (HR = 1.617; 95% CI 1.385-1.887; P < 0.0001), (0,1] (HR = 1.918; 95% CI 1.579-2.329; P < 0.0001) and (1,2] (HR = 2.016; 95% CI 1.579-2.573; P < 0.0001).

      Conclusion:
      Based on LODDS it is possible to discriminate patients with regard to lung cancer stage more effectively compared to pN and LNR classification, and it is also a better classification system. Therefore, a new system of lung cancer classification based on LODDS should be considered.

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      P1.08-002 - The Prognostic Significance of Pleural Lavage Cytology before and after Lung Resection (ID 3905)

      14:30 - 15:45  |  Author(s): Y. Yurugi, Y. Kidokoro, T. Ono, Y. Kubouchi, M. Wakahara, K. Miwa, K. Araki, Y. Taniguchi, H. Nakamura

      • Abstract
      • Slides

      Background:
      The status of intraoperative pleural lavage cytology (PLC) has been reported to be a predictive factor of recurrence in resected non-small cell lung cancer (NSCLC). However, prognostic significance of PLC remains unclear and it has not been included in the TNM classification. Furthermore, the appropriate timing to perform PLC, before lung resection (pre-PLC) or after lung resection (post-PLC), is not evident.

      Methods:
      Of 627 consecutive patients with NSCLC who underwent complete resection (segmentectomy or more) in Tottori University Hospital from January 2004 to December 2013, 615 patients who were performed both pre-PLC and post-PLC were enrolled in present study. Patients were divided into four groups, negative pre-PLC / negative post-PLC (Group A), positive pre-PLC / negative post-PLC (Group B), negative pre-PLC / positive post-PLC (Group C), and positive pre-PLC / positive post-PLC (Group D). Then differences in recurrence free survival (RFS) and disease specific survival (DSS) among each groups were analyzed by log-rank test. Moreover, PLC status as a prognostic factor for RFS and DSS were analyzed using univariate and multivariate Cox regression models.

      Results:
      There were 573 patients in Group A, 11 in Group B, 14 in Group C, and 17 in Group D, respectively. Survival analysis revealed significant differences in not only RFS but also DSS between Group A and Group B (log-rank test, p<0.001), Group A and Group C (p<0.001), Group A and Group D (p<0.001), respectively. However, there was no significant differences among Group B, C, and D (p=0.861). Multivariate analysis identified advanced age (75≤), male sex, larger tumour size (3cm<), lymphnode metastasis, lymphatic invasion, and positive PLC status (Hazard Ratio: 3.735, 95% confidence interval: 2.312 to 6.063, p<0.001) as statistically independent prognostic factors for DSS.

      Conclusion:
      In conclusion, positivity of both pre-PLC and post-PLC were significant worse prognostic factor for DSS of patients with completely resected NSCLC. Therefore, surgeons should consider performing PLC both before and after lung resection to estimate patients’ prognosis correctly. Moreover, further accumulation of knowledge about PLC are needed to reflect PLC status in the TNM classification.

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      P1.08-003 - Survival of Lung Cancer Patients was Depended on Tumor Characteristics, Blood Cell Circuit, Cell Ratio Factors, Hemostasis System (ID 3715)

      14:30 - 15:45  |  Author(s): O. Kshivets

      • Abstract
      • Slides

      Background:
      This study aimed to determine homeostasis and tumor factors for 5-year survival (5YS) of non-small cell lung cancer (LC) patients (LCP) (T1-4N0-2M0) after complete en block (R0) lobectomies/pneumonectomies (LP).

      Methods:
      We analyzed data of 676 consecutive LCP (age=57.5±8.3 years; tumor size=4.4±2.4 cm) radically operated and monitored in 1985-2016 (m=585, f=91; lobectomies=431, pneumonectomies=245, mediastinal lymph node dissection=676; combined LP with resection of trachea, carina, atrium, aorta, VCS, vena azygos, pericardium, liver, diaphragm, ribs, esophagus=188; only surgery-S=532, adjuvant chemoimmunoradiotherapy-AT=144: CAV/gemzar + cisplatin + thymalin/taktivin + radiotherapy 45-50Gy; T1=239, T2=249, T3=131, T4=57; N0=428, N1=130, N2=118, M0=676; G1=168, G2=202, G3=306; squamous=381, adenocarcinoma=249, large cell=46; early LC=134, invasive LC=542. Multivariate Cox modeling, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.

      Results:
      Overall life span (LS) was 2109.1±1692.4 days (median=1936 days) and cumulative 5-year survival (5YS) reached 69.7%, 10 years – 61.4%, 20 years – 42.9%. 419 LCP lived more than 5 years without cancer, 111 – 10 years, 14 – 20 years. 195 LCP died because of LC (LS=560±372.1 days). AT significantly improved 5YS (64.4% vs. 34.1%) (P=0.00002 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0-N12, histology, G, blood cell circuit, cell ratio factors (ratio between blood cells subpopulations and cancer cells-CC), prothrombin index, heparin tolerance, recalcification time, glucose, AT (P=0.000-0.041). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT N0-N12 (rank=1), PT early-invasive LC (rank=2), eosinophils/CC (3), prothrombin index (4), thrombocytes/CC (5), glucose (6), lymphocytes/CC (7), erythrocytes/CC (8), healthy cells/CC (9), segmented neutrophils/CC (10), stick neutrophils/CC (11), monocytes/CC (12), leucocytes/CC (13). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).

      Conclusion:
      5YS of LCP after radical procedures significantly depended on: tumor characteristics, blood cell circuit, cell ratio factors, hemostasis system and AT.

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      P1.08-004 - Prediction of Surgical Outcome by Modeling Based on Risk Factors of Morbidity Following Pulmonary Resection for Lung Cancer in the Elderly (ID 5394)

      14:30 - 15:45  |  Author(s): Y. Wang, N. Wu, J. Chen, Q. Zheng, S. Yan, S. Li, Y. Liu, Y. Yang

      • Abstract
      • Slides

      Background:
      Surgical treatment for elderly patients with lung cancer presents more challenges compared with general population. The aim of the study was to predict surgical outcome following pulmonary resection in the elderly with lung cancer by developing a clinical model.

      Methods:
      Clinical records of 525 patients aged over 70 years who underwent pulmonary resection for lung cancer in a single center were reviewed. Patients were divided into three ordered categories of surgical outcome according to the Clavien–Dindo classification. Using a development cohort of 401 patients, an ordinal logistic regression was performed to develop a prediction model for surgical outcome. The model was internally validated by bootstrap method and externally validated by another cohort of 124 patients. Two previous models were tested as benchmarks of our model.

      Results:
      The model was developed based on five risk factors of morbidity: ASA classification (p<0.001), pulmonary disease (p=0.001), tumor size (p=0.011), tumor location (p=0.015) and surgical approach (p=0.036). C-statistics of the model was similar to bootstrapping one. Hosmer-Lemeshow test showed a good goodness-of-fit. In external validation the performance of our model was superior to the two previous models. Figure 1

      Prediction Performance of the Present and Previous Models
      Models c-statistic (95%CI) Hosmer-Lemeshow test
      The present model 0.75 (0.69-0.80) 0.674
      After bootstrapping 0.75 (0.68-0.80) 0.671
      External validation 0.70 (0.64-0.75) 0.382
      Kates M, et al (2009) 0.63 (0.57-0.69) 0.115
      Poullis M, et al (2013) 0.61 (0.54-0.67) 0.091




      Conclusion:
      Our model displayed an acceptable ability to predict surgical outcome in elderly patients undergoing pulmonary resection for lung cancer.

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      P1.08-005 - Stratification of pStage I Lung Adenocarcinoma by the Scoring System Based on Prognostic Factors (ID 5168)

      14:30 - 15:45  |  Author(s): N. Kawakita, H. Toba, T. Sawada, M. Tsuboi, K. Kajiura, Y. Kawakami, M. Yoshiada, H. Takizawa, K. Kondo, A. Tangoku

      • Abstract
      • Slides

      Background:
      In Stage I lung cancer, tumor size and PL factors are only reflected by the TNM staging system. However, other clinicopathological factors have the potential to influence recurrence and prognosis, especially in pStage I lung adenocarcinoma. This study aimed to evaluate prognostic factors, and to thereby stratify pStage I lung adenocarcinoma patients.

      Methods:
      A total of 203 patients who underwent curative resection for Stage I invasive adenocarcinoma, from 2006 to 2013, were retrospectively reviewed. [18]F-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was performed in 194 patients and the maximum standardized uptake value (SUVmax) of the tumor was calculated. Invasive adenocarcinoma was classified into 3 predominant subtypes (lepidic, papillary and others) according to the IASLC/ATS/ERS classification. The associations between various clinicopathological factors and recurrence were evaluated, and disease-free survival (DFS) was analyzed.

      Results:
      Twenty-eight patients had recurrent disease during the follow-up period (mean; 59.3±25 months). Univariable analysis showed male gender, smoking history >20 pack-years, BMI≦20, CEA>5ng/ml, T classification, tumor size>20mm, predominant histologic subtype (lepidic, papillary, others), pleural invasion, vascular invasion, and SUVmax>3.0 to be significantly associated with worse DFS. On multivariable analysis, tumor size>20mm (P=0.006), papillary predominant (P=0.023), other predominant (P=0.008), and SUVmax>3.0 (P=0.008) were extracted as independent prognostic factors associated with worse DFS. Predictive variables were scored as follows; tumor size>20mm (1 point), papillary predominant (1 point), other predominant (2 points) and SUVmax >3.0 (1 point). Patients were classified into 3 risk groups (low-risk; 0-2, intermediate-risk; 3, high-risk; 4) according to their aggregate scores. The 5-year DFS rate was 91% in the low-risk group, 55% in the intermediate group and 36% in the high-risk group. The 5-year DFS rates during the same period in our institute were 88% in pStage IA, 69.5% in pStage IB, 53% in pStage II, and 38% in pStage IIIA patients. Therefore, the DFS rate in the intermediate-risk group was comparable to that of pStage II, and the DFS rate in the high-risk group was comparable to that of pStage IIIA.

      Conclusion:
      In Stage I lung adenocarcinoma, tumor size, SUVmax and histologic subtypes were suggested to be prognostic factors. This scoring system may predict the groups, such as patients with pStage II and IIIA, requiring platinum based post-operative chemotherapy.

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      P1.08-006 - Prognostic Impact of Incompletely Lobulated Fissures in Non-Small-Cell Lung Cancer (ID 4231)

      14:30 - 15:45  |  Author(s): J. Okamoto, H. Kubokura, J. Usuda

      • Abstract
      • Slides

      Background:
      The division of the incompletely lobulated fissures is often performed during the surgical resection of non-small-cell lung cancer (NSCLC). However, the influence of lobulation on tumor recurrence was unclear in these patients. Therefore, we assessed the prognostic impact of lobulation in patients with NSCLC.

      Methods:
      A retrospective study of patients with NSCLC who underwent lobectomy and bi-lobectomy was conducted between April 2008 and May 2016. Patients who underwent division of the interlobar fissure using stapling devices were compared with those who did not undergo division of the interlobar fissure.

      Results:
      A total of 126 patients with NSCLC (from p-stage IA to IIIA) who underwent surgery with (n = 103) or without (n = 23) division of the interlobar fissure were included in this analysis. No significant between-group differences were observed with respect to most variables, except for operation side (p = 0.0483), operation time (p = 0.0469), and post-operative lung comorbidity (p = 0.0031).Survival analysis revealed a significant between-group difference in disease-specific survival (DSS; p = 0.0340); however, no significant differences were observed with respect to disease-free survival (p = 0.1372) and overall survival (p = 0.0666).Cox regression univariate analysis revealed a significant association between DSS and the number of staplers used to divide the interlobar fissure (p = 0.0486).

      Conclusion:
      In this study, the extent and status of the incompletely lobulated fissures was a significant risk factor for DSS in patients with resected NSCLC.

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      P1.08-007 - The Significant Improvement of Lung Function after Preoperative Rehabilitation in Patients with Thoracic Tumors and Abnormal Spirometry (ID 3902)

      14:30 - 15:45  |  Author(s): O. Glogowska, S. Szmit, M. Glogowski

      • Abstract
      • Slides

      Background:
      The evaluation of degree of improvement of exercise tolerance and rest lung function parameters after preoperative pulmonary rehabilitation in patients with thoracic tumors and baseline borderline abnormal spirometry results.

      Methods:
      Clinical inclusion criteria were: diagnosis of thoracic tumors and reduced values of FEV1 and FVC predicting postoperative complications. We observed 29 patients (16 women, 13 men) in mean age of 68 (range 57-68) years. Spirometry, six minute walking test distance (6MWT) and maximum metabolic equivalent during exercise on treadmill (MET) were chosen for evaluation of lung function and physical performance during rehabilitation. The tests were performed twice during screening phase to eliminate the factors of learning, and were repeated after first and second week of rehabilitation. Pulmonary rehabilitation included two weeks of training on the treadmill with individually selected speed, physiotherapy exercises and breathing training with using of Triflo.

      Results:
      The significant differences were observed after pulmonary rehabilitation: 1). FEV 1 (L): 1.41 vs 1.58 (p=0.000027) 2). FEV1 (%N): 60.49 vs 71.49 (p=0.000021) 3). FVC (L): 2.34 vs 2.64 (p=0. 000520) 4). FVC (%N): 79 vs 95 (p=0.000269) 5). 6MWT Distance (m): 350 vs 400 (p=0.000007) 6). MET: 2.66 vs 2.905 (p=0.000007)

      Conclusion:
      A two-week pulmonary rehabilitation leads to significantly improvement of lung function and physical performance in patients with thoracic tumors and borderline abnormal spirometry results which may provide significantly better outcome of patients in short- and longtime follow-up.

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      P1.08-008 - Impact of Perioperative Redox Balance on Long-Term Outcome in Patients Undergoing Lung Resection (ID 3954)

      14:30 - 15:45  |  Author(s): O. Araki, T. Inoue, Y. Karube, S. Maeda, S. Kobayashi, M. Chida

      • Abstract
      • Slides

      Background:
      Surgical stress provokes a cytokine storm and systemic inflammatory response syndrome, and can also affect redox balance during the postoperative course. However, whether inflammatory status, especially redox balance, during the perioperative period has effects on long-term outcome following surgery for lung cancer remains unclear. The aim of this study was to determine whether redox balance during the perioperative period is associated with long-term survival of patients after undergoing lung resection.

      Methods:
      Consecutive patients who underwent an anatomical lung resection greater than a segmentectomy for non-small cell lung cancer from January to June 2013 at our institution were investigated. The Ethical Committee of Dokkyo Medical University Hospital approved this study (#24043) and all participating patients provided informed consent. Serum was collected during the operation, and on post-operative day (POD) 3 and 7, and the levels of reactive oxygen metabolites (d-ROM) and biological antioxidant potential (BAP) were measured using FREE carpe diem (Wismerll). We analyzed overall survival, relapse, and cause of death.

      Results:
      Twenty-two patients (males 18, females; 69±7 years old) were enrolled, of whom 12 underwent open surgery and 6 VATS. Histology findings showed 12 adenocarcinomas, 6 squamous cell carcinomas, and 4 others. Comorbidities in the patients were chronic obstructive pulmonary disease in 8 and idiopathic pulmonary fibrosis in 5. d-ROM values on POD 3 and 7 were significantly increased as compared to those obtained during the operation (perioperative 288±65, POD 3 439±49, POD 7 479±49; p<0.001), whereas BAP did not change after surgery. Overall survival was 71.4% after 3 years. A receiver operating characteristic curve revealed a dROM cut-off value of 327 during the operation. Patients with a dROM value of 327 or less showed significantly superior 3-year survival as compared to those with a greater value (87.5% vs. 20.0%, p<0.001).

      Conclusion:
      Surgical stress caused an increase in dROM during the postoperative course. The dROM value obtained during the operation was correlated with long-term survival of patients after undergoing resection for lung cancer.

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      P1.08-009 - Does Body Mass Index (BMI) Affect Outcomes Post Lung Resection Surgery? (ID 5082)

      14:30 - 15:45  |  Author(s): E. Logan, S. Avtaar Singh, T. Fujiwara, K. Graham, A. Kirk, M. Klimatsidas

      • Abstract
      • Slides

      Background:
      Increased BMI increases the surgical risk, atelectasis and postoperative complications in patients considered obese (BMI≥30). Several published studies have shown a protective effect of increased BMI. The introduction of Enhanced Recovery Programmes (ERP) in surgical units has greatly benefited obese patients in other surgical specialties but its impact in patients undergoing thoracic surgery is uncertain. We looked at the outcomes of patients at our unit since its implementation.

      Methods:
      A retrospective cohort study was performed on all patients undergoing first time lobectomies for primary lung cancer between January 2015-June 2016. Patients with BMI<18 were excluded from the study. Student’s T-test, Mann-Whitney-U Test and Chi-Squared analysis was used for statistical analysis of demographics and outcomes.

      Results:
      Figure 1 Preoperatively, the FEV1 and DLCO were both significantly higher in patients with BMI≥30. There were no statistically significant postoperative differences between the two groups.



      Conclusion:
      Patients with a BMI≥30 can do just as well as patients with BMI<30 in an ERP for patients with lung cancer undergoing lobectomy.

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      P1.08-010 - Octogenarians Perform Equally to Younger Patients in Lung Cancer Surgery (ID 4653)

      14:30 - 15:45  |  Author(s): F. Kocher, C. Ng, H. Maier, M. Sacher, G. Laimer, M. Fiegl, P. Lucciarini, T. Schmid, F. Augustin

      • Abstract

      Background:
      Due to prolonged life expectancy, more patients aged 80 years or older will be diagnosed with lung cancer and eventually undergo anatomic lung resection. This study was performed to evaluate outcome in surgically treated octogenarians compared to younger patients.

      Methods:
      The institutional database of all consecutive patients treated between 2009 and 2015 was analysed. The age cut-off was set at 80 years. Perioperative and follow-up data were compared between the two groups.

      Results:
      A total of 453 patients were treated by a VATS approach at our center for proven NSCLC. 28 (6.2%) patients were aged 80 or older. There was no difference in gender distribution, clinical T stage, preoperative FEV1/FVC and preoperative haemoglobin values. Clinical N stage was higher in the octogenarians (p=0.049). Median operative time was 175 minutes in the younger patients compared to 156 minutes in the octogenarians (p=0.104). Neither tumor diameter nor distribution of tumor histology showed any significant difference between the two groups. Postoperative haemoglobin values as a surrogate parameter for intraoperative complications were comparable between the groups. Median hospital stay was 10 days in both groups (p=0.634). There was no in-hospital mortality in the octogenarians. Disease free (72.1 vs. 58.4 months, p=0.673) and overall survival (81.7 vs. 83.8 months, p=0.456) did not show any significant difference between octogenarians and younger patients. Figure 1



      Conclusion:
      Lung resection can safely be performed in selected octogenarians with acceptable morbidity and low mortality rates. In our experience it is even as safe as in younger patients. Our data adds evidence that in such patients potentially curative treatment should not be withheld.

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      P1.08-011 - Feasibility of Surgical Resection for Lung Cancer Patients Aged over 85 Years (ID 5636)

      14:30 - 15:45  |  Author(s): T. Ouchi, A. Hattori, T. Takeshi Matsunaga, K. Takamochi, S. Oh, K. Suzuki

      • Abstract

      Background:
      Pulmonary resections for lung cancer in patients aged 80 years or over have been increasing in the aging society, which are accounted for approximately 10% in Japan. Due to the prolonged life expectancy in the elderly, it is inevitable to assess the feasibility of pulmonary resection for lung cancer especially in patients over 85 years in age.

      Methods:
      From 1995 to 2015, we underwent 3,099 pulmonary resections for lung cancers in our department. Among them, 213 (6.8%) were aged 80 years or older. They were divided into 2 groups based on the age, i.e., “Over80” who were aged from 80 to 84 and “Over85” who were aged 85 or elder. Clinicopathological factors were analyzed between these two groups, using the t-test or the Chi-squared test. Survivals were calculated by Kaplan-Meier estimation methods.

      Results:
      Of the cases, 174 (84%) showed Over80 and 39 (18%) showed Over85. The proportions for male, comorbidity rate, c-stage I disease in the Over85 group were not significantly different than those of the Over80 group (age; 20 (51%) vs. 105 (60%), p=0.189: comorbidity; 36 (92%) vs. 154 (89%), p=0.489: c-stage I; 36 (92%) vs. 143 (82%), p=0.119). The surgical candidates of the octogenarian included 167 (78%) radiological pure-solid lung cancer, however, there was not significant difference between the 2 groups (28 (72%) vs. 139 (80%), p=0.267). Lobectomy was equally performed in 28 (72%) on the Over85 and 126 (72%) of the Over80 (p=0.938), respectively. Perioperative morbidities were observed in 104 (48%) of the patients, though, significant difference was not found between the two study arms (84 (48%) vs. 20 (51%), p=0.734) and the 30-day mortality rates was observed just one patient for the Over80 group. The 5-year overall survival was 51.1% in the Over80 group, 62.6% in the Over85 group (p=0.275), respectively.

      Conclusion:
      In the octogenarians, a patient with radiological pure-solid lung cancer was more common as a surgical candidate for the definitive local management. Although proper patient selection and meticulous perioperative management were mandatory for surgical resection of the very elderly, our results support the finding that radical surgical intervention could be feasible even for the patients with high age over 85 years.

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      P1.08-012 - Characterizing Time to Care for Lung Cancer Surgical Patients (ID 6168)

      14:30 - 15:45  |  Author(s): B. Cadham, J. Olsen, R. Rajapakshe, M. Humer

      • Abstract

      Background:
      The Kelowna Thoracic Surgical Group (KTSG), centered in Kelowna, British Columbia (BC), Canada provides care to a geographic area of 807,538 km[2]. This is 85% of the province of BC and approximately 9 times the size of Austria. A significant portion of this population consists of remote and rural communities. Ensuring equal and prompt access to lung cancer diagnosis and treatment regardless of proximity to treatment center is important not only because of the time sensitivity of care, but also because of the overall healthcare burden of this highly prevalent and often lethal malignancy.

      Methods:
      A retrospective chart review was performed on all patients seen by the KTSG who came to definitive surgical treatment in Kelowna for a diagnosed or suspected lung cancer between January 2010 and December 2015. Dates were collected at three time-points along the care pathway: Referral, Consult, and Surgical Treatment. We calculated times from referral to consult (RC), consult to treatment (CT), and overall referral to treatment (RT). Demographic information was collected for each of the patients and the distances patients’ lived from the Surgical Centre were determined. The study has received approval from both University of British Columbia – BC Cancer Agency and Interior Health Authority research ethics boards.

      Results:
      There were 902 patients in the cohort; 446 local patients who lived within a radius of 100 km or less from Kelowna and 456 distant patients who resided further than 100 km from the city. For the entire group, the median RT was 50.5 days comprised of RC = 6 days, and CT = 42 days. For the local patient group, the median RT was 49 (Interquartile Range (IQR) = 33.75 to 69) days compared to a median of 52.5 (IQR = 36 to 52.5) days for the distant patients. The extreme overlap in the IQR shows no significant clinical difference in time to care between the local and distant patients.

      Conclusion:
      Time from referral to treatment for patients with suspected or confirmed lung cancer seen by the IHTSG is similar for both local and distant patients. The equitable times to care with the IHTSG suggests that the current model of patient-doctor communication provides a growing opportunity to mitigate the impact of distance on access to care.

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      P1.08-013 - Preoperative Managements for Pulmonary Complications Using Inhalations in Lung Cancer Patients with Chronic Obstructive Pulmonary Disease (ID 5566)

      14:30 - 15:45  |  Author(s): K. Takegahara, J. Usuda

      • Abstract
      • Slides

      Background:
      Chronic obstructive pulmonary disease (COPD) is related to the prognosis of patients with lung cancer, and one of risk factors of respiratory complications after surgical resections. This study aimed to investigate whether perioperative inhalations of long-acting beta-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) would decrease the postoperative complications in lung cancer patients with COPD.

      Methods:
      We retrospectively analyzed 108 patients with COPD who underwent pulmonary resections for primary lung cancer at our hospital between January 2013 and January 2016, in order to determine the association between the incidence of postoperative complications (e.g., prolonged air leakage and pneumonia) and the use of LABAs or LAMAs.

      Results:
      Among 108 patients with COPD patients, there were 86 men and 22 women, with a mean age of 69.3 years (range, 46–84). The mean Brinkman index was 1172.1(range, 50-3480). The mean FEV1.0/FVC was 61.4%(range, 26.8%-69.9%). The surgical procedures were partial resection in 11 patients, pulmonary segmentectomy in 3 patients, lobectomy in 92 patients, and pneumonectomy in 2 patients. The histological types showed adenocarcinoma in 53 patients, squamous cell carcinoma in 38 patients, adenosquamous carcinoma in 5 patients, large cell neuroendocrine carcinoma in 3 patients, large cell carcinoma in 4 patients, small cell carcinoma in one patient, and pleomorphic carcinoma in 4 patients. There were 29 postoperative complications in COPD (26.9%), prolonged air leak (more than 7 days) 14 cases, pneumonia 9 cases, arrhythmia 2 cases, chylothorax 2 cases, wound infection 2 cases. The frequency of postoperative pulmonary complications such as prolonged air leakage and pneumonia, was significant higher in COPD (23 cases, 21.3%) than in non COPD (15 cases,6.7%). Inhaled bronchodilators such as LAMA or LABA were prescribed to 34 cases in COPD, not to 74 cases. The pulmonary complications were significant lower in LAMA or LABA users (3 cases, 8.8%) than in no users (20 cases, 27.0%).

      Conclusion:
      For lung cancer patients with COPD, preoperative management using the inhalants with LABA or LAMA, and smoking cessation can reduce the frequency of the postoperative pulmonary complications after surgical lung resection. The inhalants with LAMA or LABA may be adapted for the management of not only perioperative care but also long-term survival of COPD patients after surgery.

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      P1.08-014 - Usefulness of Chest CT in Follow-Up of Patients with Completely Resected Lung Cancer (ID 5264)

      14:30 - 15:45  |  Author(s): J.L. Gross, J.B.F. Morelato, M.D. Guimarães, F.J. Haddad, J.P.O. Medici, M.V.B. Baranauskas, H.A. Carneiro, M.L.L. Medeiros

      • Abstract

      Background:
      There is no consensus about the best method to follow up patients after complete resection of lung cancer. This study was performed to identify how often follow-up chest-CT detected recurrence or a second primary lung cancer in asymptomatic patients.

      Methods:
      This is a retrospective study. Patients with diagnosis of non-small cell lung cancer submitted to complete surgical resection were included. They were followed-up with regular visits to the clinic and chest CTs. The visits to the clinic were every three months in the first two years, semiannually up to the fifth year, and annually thereafter. Patients were classified in symptomatic and asymptomatic according to the presence of clinical manifestations at each visit.

      Results:
      From 2003 to 2013, 134 patients were included. Median age was 63.5 years. Seventy three (54.5%) were male. Current or former-smokers were 70.1% of the patients. Adenocarcinoma was the most common histologic type, observed in 82 (61.2%) of the patients. Lobectomy/bilobectomy was performed in 99 (73.8%), segmentectomy in 31 (23.1%), and pneumonectomy in 4 (3%). Pathological stage was: IA(53%), IB(10.2%), IIA(11.7%), IIB(6,6%), IIIA(13.3%), IIIB(3.1%), and IV (2.1%). Forty six (44.3%) patients were submitted to adjuvant treatment. Median follow-up was 30.2 months. Recurrence was detected in 18 (13.4%) patients, being local (including mediastinal) in 10 (7.4%), and distant in 8 (5.9%). Local recurrences were mainly detected by chest CT in asymptomatic patients. Distant recurrence was detected mostly by clinical symptoms (Table 1). Second primary lung cancers were found by chest CT in 15 (11.2%) asymptomatic patients. Table 1 – Correlation between type of recurrence and presence of symptoms.

      Local recurrence Distant recurrence
      CT (Asymptomatic) 9 (90%) 2 (25%)
      CT (Symptomatic) 1 (10%) 6 (75%)
      Total 10 (100%) 8 (100%)
      p = 0.09

      Conclusion:
      Routine chest-CT detected most cases of local recurrence and second primary lung cancers in asymptomatic patients after curative resection of non-small cell lung cancer. Clinical examination and chest CT should be recommended for follow up after complete surgical resection.

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      P1.08-015 - Surgery of Stage I Non-Small Cell Lung Cancer in Patients Aged 80 Years or Older (ID 3921)

      14:30 - 15:45  |  Author(s): O. Kawamata

      • Abstract
      • Slides

      Background:
      Non-small cell lung cancer (NSCLC) is a typical disease of the elderly patients, and is becoming increasingly. Surgical resection is standard treatment for early-stage NSCLC. We evaluate the efficacy of lobectomy versus segmentectomy for stage I non- small cell lung cancer in elderly patients 80 years or older.

      Methods:
      54 cases with stage I of 82 patients aged 80 years or older who underwent surgery for non-small cell lung cancer at our hospital between 2004 and 2013 were studied. The patients’ medical records were reviewed with type of operation, histological diagnosis, postoperative morbidity, postoperative mortality and survival results.

      Results:
      There were 33 men and 21 women. The average ages were 83.4 years (range, 80-90 years). Adenocarcinoma was identified in 45 patients and squamous cell carcinoma was identified 9 patients. Lobectomy was performed in 25 patients for stage IA (n=10) and IB (n=15), segmentectomy was performed in 18 patients for stage IA (n=15) and IB (n=3) and wedge resection was performed in 11 patients for stage IA (n=10) and IB (n=1). Mean follow-up was 53 months. 4 cases of 54 patients died for lung cancer and 8 cases died for other causes within 5 years after lung resection. Overall survival rate at 5 years in all patients was 70.6%. One case of 25 patients who underwent lobectomy died for lung cancer (IA n=1, IB n=0). 3 cases died for other causes (IA n=1, IB n=2). Two cases of 18 patients who underwent segmentectomy died for lung cancer (IA n=0, IB n=2), 3 cases died for other causes (IA n=2, IB n=1). Overall survival rate at 5 years for lovectomy vs segmentectomy was 74.5% vs 68.1% (IA; 67.5% vs 86.7%, IB; 77.0% vs 0%). Morbidity rate in all patients was 22.2% (lobectomy; 20.0% vs segmentectomy; 27.8%), atrial fibrillation 5 patients (3 vs 2), heart failure 1 patient (0 vs 1), prolonged air leakage 3 patients (1 vs 2), atelectasis 2 patients (0 vs 2), delirium 1 patient (1 vs 0). Mortality rate was 0% in both groups.

      Conclusion:
      The lobectomy and segmentectomy were equal results in elderly patients 80 years or older for stage IA NSCLC. These data further support the use of lobectomy for resection of stage IB tumors.

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      P1.08-016 - BMI in Patients with Operated Lung Cancer in Comparison with the Scottish Health Survey 2014. Is There a Democracy in BMI? (ID 4388)

      14:30 - 15:45  |  Author(s): T. Fujiwara, S. Avtaar Singh, A. Kirk, M. Klimatsidas

      • Abstract
      • Slides

      Background:
      Lung cancer has the most common cancer related mortality in Scotland¹. Malnutrition is common in these patients and may affect survival². However many patients with operable lung cancer are overweight³. We looked at lung cancer resection rates at our unit and compared it to the Scottish Health Survey (SHS) 2014.

      Methods:
      A retrospective cohort study of all patients undergoing lobectomy and pneumonectomy for pathologically proven primary lung cancer from April 2012 to May 2016.

      Results:
      5833 patients have been operated in our centre during the period, 1882 had anatomical lung resections and 979 of these were eligible to enter our study. Mean age of male patients was 68±9.5 years and female patients was 66.7 ±9.0 years. The median length of stay for males and females were 8 (Q1=6, Q3=12) and 7 (Q1=6, Q3=10) days respectively. The Chi squared test for trend for males showed X²(1) =0.07, 2p=0.8, females showed X²(1) =0.00, 2p=1.0. There was no statistical difference for both males and females BMI distribution between the SHS and our cohort.

      BMI males females
      <18.5kg/m² 8 15
      18.5-24.9kg/m[2] 106 155
      25-29.9kg/m[2] 146 135
      30-39.9kg/m[2] 90 123
      >40kg/m[2] 1 13
      total *BMI not recorded (missing data) 351 89 441 98
      Figure 1



      Conclusion:
      Our study reveal that the rate of resection in our cohort was similar to the SHS. Further studies will be required to look into the relationship between surgical outcomes and BMI.

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      P1.08-017 - Does Mediastinal Lymph Node Dissection Affect Prognosis of Early Stage NSCLC? (ID 6087)

      14:30 - 15:45  |  Author(s): H. Kim, W.S. Chung, H. Kim

      • Abstract
      • Slides

      Background:
      Adequate staging is important in treatment of non-small cell lung cancer (NSCLC). Owing to innovation of imaging tools, the preoperative clinical staging is accurate while surgical staging is still a golden standard. For complete resection of NSCLC, a systematic nodal dissection is recommended in all cases. However, for peripheral T1 tumor, a more selective nodal dissection depending on the lobar location of the primary tumor (lobe-specific systematic nodal dissection) is acceptable. In this study, we try to evaluate more selective lymph node sampling is acceptable in early stage NSCLC; stage IA and IB.

      Methods:

      Stage IA (n=86) Stage IB (n=44)
      Lobe-Specific LN Dissection vs LN Sampling
      Lobe-Specific LN Dissection 30 17
      LN Sampling 56 27
      Adequate LN Dissection vs LN Sampling
      Adequate LN Dissection 32 17
      LN Sampling 54 27
      From January 2011 to December 2015, 186 patients underwent surgical treatment at out center. Among them 130 patients were stage IA and IB. We retrospectively reviewed medical records and classified patients into two groups by lymph node dissection (LND) method. When we perform LN smapling, the intraoperative frozen section diagnosis for dissected LNs is routine procedure in our center. Survival analysis to evaluate effect of LND on cancer recurrence was performed.

      Results:
      In survival analysis, the risk of recurrence between two groups was not significantly different. The patients who underwent lobe-specific LND did not show superior survival (p=0.598) It was same in the patient who underwent adequate LND mentioned in AJCC guidelines (p=0.714). The difference in risk of recurrence was not presented in stratified analysis by stage.

      Conclusion:
      In early stage lung cancer, the possibility of hidden LN metastasis is very low. Therefore, limited LN dissection such as LN sampling based on the result of intraoperative frozen section diagnosis can be acceptable in surgery for early stage NSCLC.

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      P1.08-018 - Positive N Stage is a Risk Factor for Survival in Five-Year Disease Free Survivors with Completely Resected Non-Small Cell Lung Cancer (ID 3935)

      14:30 - 15:45  |  Author(s): J.G. Lee, S. Lee, C.Y. Lee, D.J. Kim, K.Y. Chung

      • Abstract

      Background:
      Lung cancer has a poor prognosis and it has a small number of long term survival patients compared to other cancers. Therefore, there is a limitation in evaluating survival beyond 5 years after surgical treatment. The purpose of this study is to analyze risk factors of survival and late recurrence in these patients after 5 years disease free period.

      Methods:
      This is a retrospective analysis of patients who had at least 5 years disease free survival after surgical treatment for NSCLC at a single institute between January 1998 and December 2007. We excluded patients who received neo-adjuvant therapy, incomplete resection, or advanced stage (stage IIIb and IV).

      Results:
      463 (41.1%) out of 1126 patients were enrolled. 318 patients (68.7%) were male, and their mean age was 61.3 ± 9.7 years (range, 21.3 – 82.2). Pathologic N0 (337 patents, 72.8 %) and stage I (263 patents, 56.8 %) were dominant stage. Late recurrence occurred in 5.4 % (25 patients) after 5 years of surgery. In multivariate analysis, male, age (≤ 60 years), node positive, and late recurrence were independent risk factors for overall survival, while the node positive was the only independent risk factor for disease free survival on multivariate analysis (HR, 2.609; p=0.017; CI, 1.190 – 5.719).

      Table. Multivariate analysis of Overall Survival & Disease Free Survival
      Variables HR p 95% CI
      Overall Survival
      Sex
      Female 1
      Male 2.243 0.003 1.323-3.801
      Age
      age < 60 1
      60 ≤ age <70 2.647 <0.001 1.593-4.398
      70 ≤ age 4.607 <0.001 2.605-8.149
      p-N stage
      N0 1
      N1+N2 1.809 0.003 1.231-2.660
      Recurrence
      No 1
      Yes 5.377 <0.001 3.316-8.719
      Disease free survival
      p-N stage
      N0 1
      N1+N2 2.609 0.017 1.190-5.719


      Conclusion:
      This study confirmed that late recurrence occurred in patients with no recurrence for 5 years after surgical resection, and it had a negative effect on overall survival beyond 5 years after operation. Furthermore, N positive (N1 or N2) was an independent risk factor for both overall survival and disease free survival. Therefore, careful follow-up is needed for the detection of late recurrence even in patients with five years disease free survival, and especially for node-positive patients. More studies are needed to clarify this point.

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      P1.08-019 - Risk Factors and Survival of Occult N2 Lymph Node Metastasis in NSCLC Patients with Clinical N0-1 Diagnosed by Preoperative PET-CT (ID 5131)

      14:30 - 15:45  |  Author(s): K. Park, C. Bae, E. Lee

      • Abstract
      • Slides

      Background:
      Accurate staging of NSCLC for N2 lymph node metastasis is crucial for prognosis and optimal therapy. Suggestion of occult mediastinal lymph node metastasis could help physicians for decision making of staging and management. This study was aimed to know risk factors and survival for occult N2 lymph node metastasis in NSCLC patients with clinical N0 and N1 diagnosed by preoperative PET-CT.

      Methods:
      This study was evaluated NSCLC patients with clinical N0-1 who underwent R0 lung resection with complete lymphadenectomy. Clinicopathological factors such as tumor size, tumor location, tumor laterality, histology, and FDG uptake were analyzed to delineate risk factors. Overall survival was analyzed.

      Results:
      Between November 2005 to December 2014, the incidence of N2 lymph node metastasis was 13.3%(22 patients of 166). The risk factors for pN2 were central located tumor(p<0.001), larger tumor size on CT(p=0.038), and high SUV on PET(p=0.001). Patients having risk factor of central tumor had shorter survival, significantly(p<0.001).

      Conclusion:
      The central located tumor, larger tumor size on CT, and high SUV of primary tumor were predictable factors for N2 lymph node metastasis in clinical N0-1 NSCLC. Therefore, these factors may help determined whether to enforce cN0-1 patients to do mediastinal staging selectively.

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      P1.08-020 - The Effect of Two Interventions on Attainment of Surgical Quality Measures in Resected Non-Small Cell Lung Cancer (NSCLC) (ID 5694)

      14:30 - 15:45  |  Author(s): N.R. Faris, M.A. Ray, M.P. Smeltzer, C. Fehnel, C. Houston-Harris, P. Levy, C. Mutrie, B.A. Wolf, L. Deese, L. Wiggins, V. Sachdev, S. Signore, E.T. Robbins, R.U. Osarogiagbon

      • Abstract
      • Slides

      Background:
      Better pathologic staging improves early-stage NSCLC survival. We sought to measure the impact of complementary surgery (lymph node specimen collection kit) and pathology (a novel gross dissection method) interventions on attainment of guideline-recommended surgical staging quality.

      Methods:
      We analyzed curative-intent resections from 2004-2016 from 4 contiguous Dartmouth Hospital Referral Regions in 3 US states. Preoperatively-treated patients were excluded. Patients were categorized into groups based on whether a lymph node specimen collection kit was used during surgical resection, and whether a novel, anatomically-sound gross dissection method was used to retrieve intrapulmonary lymph nodes. Chi-squared tests were used to examine differences in demographic and disease characteristics and surgical quality parameters across implementation groups.

      Results:
      Of 2,094 patients, 1,492 received neither intervention; 152 received only the pathology intervention; 161 received only the surgery intervention; 289 had both (Table 1). Attainment of surgical quality guidelines significantly increased in ascending order of the pathology, kit, and combined interventions (Table 2). Figure 1 Figure 2





      Conclusion:
      The combined effect of two interventions to improve pathologic lymph node examination has a greater effect on attainment of a range of surgical quality parameters than either intervention alone.

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      P1.08-021 - Predictors of Post-Operative Mortality in Non-Small Cell Lung Cancer (NSCLC) in a High Mortality Region of the US (ID 4447)

      14:30 - 15:45  |  Author(s): M.P. Smeltzer, Y. Lee, E.T. Robbins, N.R. Faris, C. Mutrie, M.A. Ray, S. Signore, C. Fehnel, C. Houston-Harris, M.B. Meadows, R.U. Osarogiagbon

      • Abstract
      • Slides

      Background:
      Surgical resection is recommended for most patients with early-stage NSCLC. High postoperative mortality risk diminishes the benefit of curative-intent surgery. We examined factors associated with mortality within 120 days of curative-intent resection in a population-based cohort.

      Methods:
      We examined all NSCLC patients with curative-intent resections from 2009-2016 in all 11 hospitals in 4 US Dartmouth Referral Regions. We evaluated patient demographics, disease characteristics, pre-operative evaluation, treatment, and perioperative complications to identify risk factors for 30-, 60-, 90-, and 120-day mortality using logistic regression models.

      Results:
      The 2,258 patients’ median age was 67, 48% were female; 78% were White, 21% Black. The 30-, 60-, 90-, and 120-day post-operative mortality rates were 4%, 6%, 8%, and 9%. After adjusting for all other factors, American Society of Anesthesiologists score (ASA) (p=0.0405), prior lung cancer (p=0.0406), and Charlson comorbidity score (p=0.0163) were associated with 30-day mortality. Adjusted models for 120-day mortality indicate associations with age (p=0.0001), tumor size (p=0.0012), intra-operative blood loss (p=0.0150), hospital (p=0.0065), ASA (p=0.0035), prior lung cancer (p=0.0466), and Charlson score (p=0.0064) (Table 1). Patients >75 years old had 1.5 times the odds of 120-day mortality compared with those <49. A Charlson score >=3 (vs. 0) conferred 2.7 times the odds of 120-day mortality. On average, each 1 cm increase in tumor size increased the odds of 120-day mortality by 12%. Patients with all three risk factors (age >75, Charlson score >=3, tumor >4cm) had 26.5% 120-day mortality. Although 17.5% of pneumonectomy patients died within 120 days, extent or duration of surgery were not significant after adjusting for other factors.

      N (total=2258) 30-Day Mortality 120-Day Mortality
      % %
      Age
      < 49 101 3 7.9
      50-64 730 2.6 4.3
      65-74 937 4.7 9.9
      75+ 490 6.1 13.1
      p=0.1954 p=0.0001
      Tumor Size(mean) 2258 3.6 3.9
      p=0.1834 p=0.0012
      Surgery Type
      Lobectomy/Wedge 1696 3.5 7.8
      Pneumonectomy 143 9.1 17.5
      Bilobectomy 126 6.4 11.9
      Segmentectomy/Wedge 293 5.5 7.9
      p=0.4359 p=0.6029
      Previous Lung Cancer
      No 2166 4 8.3
      Yes 92 10.9 17.4
      p=0.0406 p=0.0466
      Charlson Comorbidity
      0 455 1.8 4.2
      1-2 1132 3.8 8.2
      ≥3 671 6.7 12.5
      p=0.0163 p=0.0064
      Blood loss(surgical)
      0-500cc 2048 4 7.8
      501-1000cc 136 6.6 16.9
      >1000cc 74 8.1 18.9
      p=0.4842 p=0.015


      Conclusion:
      Age, ASA, Charlson score, and tumor size are important risk factors for post-operative mortality. Inter-hospital disparity suggests an opportunity for institution-level corrective interventions. Patients with the combination of age >75, Charlson score >=3, and advanced T-category had a high rate of post-operative mortality.

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      P1.08-022 - Risk Stratification Model to Predict Survival Following Surgical Resection for Lung Cancer Using Pathological Variables (ID 4495)

      14:30 - 15:45  |  Author(s): T. Edwards, C. Tennyson, H. Balata, P. Foden, A. Chaturvedi, R. Shah, P. Crosbie, R. Booton, M. Evison

      • Abstract
      • Slides

      Background:
      The risk of lung cancer recurrence remains a significant problem following curative-intent treatment. Novel methods of calculating this risk may have potential benefits in defining adjuvant strategies and stratifying the intensity of surveillance programs. The aim of this study was to identify factors at surgical resection of NSCLC that influenced survival in attempt to develop a probability model to predict mortality.

      Methods:
      Pathological variables were recorded from 1311 patients undergoing surgical resection for NSCLC from 2011 to 2014 at a tertiary UK lung cancer centre. Pathological variables analysed included T-stage, N-stage, adequacy of intra-operative lymph node sampling, pleural invasion, lymphovascular invasion, extracapsular spread, histological sub-typing, extent of surgery, grade of differentiation and R status (residual disease). Survival data was obtained from national death registries and logistic regression was used to develop a probability model to predict mortality.

      Results:
      Table 1. Pathological predictors of survival 1 year post surgery for NSCLC Figure 1 Using the probabilities from the logistic regression model to predict one year mortality gives an AUC of 0.741. If a probability of 0.144 is used to predict whether a patient will die within one year of surgery, sensitivity is 70.0% (119/170), specificity is 67.3% (625/929), PPV is 28.1% (119/423) and NPV is 92.5% (625/676).



      Conclusion:
      Survival post-curative intent surgery for NSCLC is based on multiple pathological factors as described above. Further analysis of these factors will be performed in the future to determine a risk stratification model to predict patients with low versus high risk mortality post surgery. Whilst indications for adjuvant therapy are well documented, the optimal surveillance regime is not as clear. Given the heterogenous group of patients receiving surgery for NSCLC, a predictive model may be useful in determining optimal surveillance strategies.

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      P1.08-023 - Analysis of Prognostic Factors and Long-Term Results of Primary Pulmonary Pleomorphic Carcinoma (ID 6191)

      14:30 - 15:45  |  Author(s): D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari

      • Abstract

      Background:
      Pulmonary pleomorphic carcinoma (PPC) is a rare neoplasm and factors affecting survival after pulmonary resection, as well as its clinical and pathologic characteristics, are still unknown. For a better understanding we reviewed our large experience with these patients.

      Methods:
      Records of patients 134 patients (108 men, median age: 65 years) with diagnosis of PPC operated on between January 1999 and May 2015 were retrospectively analyzed from a prospective database; survival was calculated by using Kaplan-Meier method.

      Results:
      86 patients (64.1%) were smokers. Median tumor size was 4.8 cm (range, 0.6 to 23 cm). Initial histological diagnosis was NSCLC in 88 cases, adenocarcinoma in 21, pleomorphic tumor in 13, and no diagnosis in 12. 62 patients (46.0%) received a platinum based induction chemotherapy. Surgery included lobectomy in 87 patients (65%), pneumonectomy in 27 (20.1%), wedge resection in 12 (8.9%), and segmentectomy in 8 (6%). Four patients (3%) had an incomplete resection. Postoperative staging included 45 stage I (33.6%), 47 stage II (35.1%), and 42 stage III (31.3%). 64 patients (47.7%) received adjuvant treatment. Five-year overall survival and disease-free survival were 36.6% and 35.7%, respectively (median, 28 and 18 months, respectively). Recurrences occurred in 76 patients (56.7%) most of them at distant sites (47/76 [61.8%]). Factors associated with increased survival included no smoke habit (p=.02), no induction therapy (p=.04), right side disease (p=.01); pathological stage I (p=.001), no metastatic lymph nodes (p=.001), and adjuvant treatment (p=.003). At multivariate analysis, pN0, pstage I, and adjuvant treatment were independent prognostic factors (p=.002, 95%CI: 1.54-6.43; p=.003, 95%CI: 1.23-7.32, p=.001, 95%CI: 1.26-4.72, respectively).

      Conclusion:
      PPC are aggressive tumors usually presented as a large lesion in males. Preoperative diagnosis remains difficult. Prognosis is poor, and distant recurrence rate is high. Long-term survival can be achieved in early stage disease and by an appropriate adjuvant therapy.

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      P1.08-024 - Surgical Outcomes and Prognostic Factors in the Treatment of Adenosquamous Carcinoma of the Lung (ID 6200)

      14:30 - 15:45  |  Author(s): D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari

      • Abstract

      Background:
      Adenosquamous carcinoma (ASC) of the lung is a rare pulmonary disease with poor prognosis. We evaluated the prognostic factors and outcome of this tumour.

      Methods:
      Records of patients undergoing pulmonary resection for ASC between 1998 through 2015 were reviewed using a prospective database. 124 patients (91 men, median age, 67 years) with ASC were operated on.

      Results:
      Surgical procedures included 3 exploratory thoracotomies, 6 bilobectomies, 76 lobectomies, 19 pneumonectomies, 12 wedges resections, and 8 segmentectomies. 38 patients (30.6%) received induction therapy (IT). 30-day mortality rate was 4.0% (n=5). Morbidity occurred in 29 (23.4%) patients; six patients (4.8%) had major complications: 2 bronchopleural fistulae, 3 haemothoraces, and 1 chylothorax. 23 patients (18.6%) had early minor complications: 14 (11.2%) atrial fibrillation, and 9 (7.2%) pulmonary (5 prolonged air leaks, 2 atelectasis and 2 subcutaneous emphysema). Overall 5-year survival rate and disease-free survival was 27.4% and 36.0%, respectively. 47 (37.9%) patients relapsed: 14 had brain metastases, 10 bone, 8 lung, and 15 at other sites. Patients <65 years (p=0.01), with early pathological stage (p=0.0001), without nodal involvement (p=0.001) had the best prognosis. At multivariate analysis, age <65 years (p=0.009 [95% CI 2.53-8.29]), early pathological stage (p=0.04 [95% CI 1.66-7.88]), and no nodal involvement (p=0.03 [95% CI 2.01-6.42]) influenced survival.

      Conclusion:
      ASCs are uncommon and extremely aggressive tumours. Young patients (<65 years) with early stage tumour and no nodal involvement have the best prognosis.

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      P1.08-025 - Long-Term Survival of Lung Cancer in Chile (ID 6223)

      14:30 - 15:45  |  Author(s): R. Valenzuela, C. Suárez, M. Fica, F. Suárez, R. Aparicio, V. Linacre, J.L. Lobos, R. Villarroel

      • Abstract
      • Slides

      Background:
      Lung cancer is the leading cause of cancer death worldwide. The long-term survival is an important outcome of oncologic therapies. In early stages permits to evaluate the quality of surgical oncology services, meanwhile in advanced stages the quality of the multidisciplinary teams. Screening programs and early diagnosis are the most efficient way to achieve increase in overall survival. The results of Clínica Santa Maria in Lung Cancer patients are presented.

      Methods:
      All patients diagnosed with Non-small Lung Cancer, treated by the team of Thoracic Surgery in our private hospital, during the period January 2011 to July 2016 were entered prospectively, consecutively and daily to a web database. Demographic, clinical and pathological data, as well as monitoring all events were recorded. All our patients underwent to an exhaustive staging process. Statistical descriptive analysis of clinical and demographic variables and 5 year overall survival are shown.

      Results:
      313 patients were included, median age of 65 years old (32-89), 48,6% female. Adenocarcinoma was the most frequent histology (78,9%). Stage I 48,6%, ​​Stage II 9,27%, Stage III 14,8%, and Stage IV 26,5%. The median follow-up time was 50 months (1-289) with a mean survival time of 99 months. Overall 5-year survival was 63,7% (95%CI, 57-69%), and by stages: Stage I 91,4% (95%CI, 84,9-95,2%), Stage II 63,7% (95%CI, 39,5-80,3%), Stage III 44,3% (95%CI, 26,4-60,8%) and Stage IV 19,1% (95%CI, 10,1-30,3%). Adenocarcinomas was 64% (95%CI, 56,6-70,5%). Figure 1



      Conclusion:
      The epidemiological profile of our patients is similar to those published in most of the World Series. The diagnosis in early stages is high, further up than most publications, however, lower than those shown by Asamura, who reported 58,6%. We believe that the overall survival of this series results are superior to most international publications, due to the high percentage of patients in early stages, exhaustive staging and adequate multidisciplinary treatment.

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      P1.08-026 - LUNG CANCER - Early and Late Outcomes of Surgical Patients of a New District Hospital  (ID 6245)

      14:30 - 15:45  |  Author(s): P.A. Calvinho, J.P. Santos, C. Matos, M. Felizardo, S. Furtado

      • Abstract

      Background:
      To compare surgical patient outcomes of a new district hospital with the expected results described in the literature.

      Methods:
      From March 2012 to December 2015, 288 lung cancer patients were treated in our hospital, of which 58 were operated on. All patients were discussed at a multidisciplinary team. The mean age at diagnosis was 64.6+9.2y yrs, being 69% males. At the time of diagnosis, 45 had history of smoking, 28 filled the criteria of COPD, 2 had history of tuberculosis, 2 had type 2 diabetes, 37 had history of cardiovascular disease, 8 had history of other cancer and 3 had chronic renal disease. As for tumour types, the majority was adenocarcinoma (34), followed by squamous cell (18), carcinoid tumour (3), SCLC (1), adenosquamous (1) and poorly differentiated lung cancer (1). One patient had 2 synchronous tumours and two patients developed a new type of tumour during follow-up. As for staging, the majority of patients were in clinical stage IA (20) and the rest distributed as follows: IB - 13 pts, IIA - 4 pts, IIB - 4 pts, IIIA - 10 pts, IIIB - 1 pt and IV - 6 pts. At the time of pathological staging 1 was up-staged and 1 down-staged. In stage IV patients, 4 surgeries were performed with paliative intent and 2 with curative intent. In 17.2% patients was given neo-adjuvant chemotherapy, and 44.8% received adjvant chemotherapy. We performed 64 surgeries (41 lobectomies with lymphadenectomy (11 VATS); 6 bilobectomies; 3 pneumectomies; 6 wedge resections; 1 exploratory thoracotomy and 3 mediastinoscopies.

      Results:
      There was no perioperative mortality. Eight patients had major complications (6 - post-operative pneumonia). The mean follow-up time was 21+11 months with an overall mortality of 15.5%. Stage related mortality: for stages IA and IB the overall survival was 100% with mean follow-up time of 23 months, in stage IIA the overall survival was 83.4% with mean follow-up time of 28 months, in stage IIB the overall survival was 75% with mean follow-up time of 24 months, in stage IIIA the overall survival was 70% with mean follow-up time of 20 months and in stage IV the overall survival was 33.3% with mean follow-up time of 18 months.

      Conclusion:
      These outcomes overlap those reported in recent data from the literature. Although our Hospital is a low/medium volume centre for Lung Cancer we show with these data that with a dedicated multidisciplinary team it is possible to replicate the international results.

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      P1.08-027 - Evolution of Survival in a Regional Population-Based US Lung Cancer Resection Cohort (ID 6122)

      14:30 - 15:45  |  Author(s): R.U. Osarogiagbon, N.R. Faris, M.P. Smeltzer, M.A. Ray, C. Fehnel, C. Houston-Harris, P. Levy, C. Mutrie, B.A. Wolf, L. Deese, L. Wiggins, V. Sachdev, S. Signore, E.T. Robbins

      • Abstract

      Background:
      Quality variances in surgical resection and pathology examination practice translate into survival disparity in patients with early stage lung cancer after curative-intent resection. We evaluated the survival patients from two eras in a US regional cohort.

      Methods:
      All curative-intent lung cancer resections in 11 US hospitals in 4 contiguous Dartmouth Hospital Referral Regions were analyzed for stage-stratified survival before and after an ongoing regional quality improvement campaign started in 2009. Overall and stage-stratified survival of patients with surgery in the 2004-2009 (pre-era) v 2010-2015 (post-era) were compared using the log-rank test and Cox proportional hazards models.

      Results:
      Of the total cohort of 3246 patients, 40.6% were in the earlier era, 59.4% in the later era. Demographic characteristics were similar between cohorts (Table 1). Preoperative PET/CT, brain MRI scans, bronchoscopy, and adjuvant therapy were more frequently used in the later era. Patients in the early era had an unadjusted hazard ratio (HR) of 1.22 (p=0.0006). After controlling for stage, tumor size, neoadjuvant therapy, comorbidity score, grade, extent of surgery, patients in the pre-era had a HR of 1.49 (p<0.0001). Figure 1Figure 2





      Conclusion:
      Survival has improved since introduction of a regional quality improvement campaign in a high lung cancer mortality region of the US.

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      P1.08-028 - Nationwide Trends in Surgery for Lung Cancer in Finland from 2004 to 2014 (ID 4143)

      14:30 - 15:45  |  Author(s): J.M. Gunn, V. Kytö

      • Abstract
      • Slides

      Background:
      Surgical treatment for lung cancer has developed in recent decades and has enabled surgical treatment of patients with increasingly severe comorbidities. The aim of this study is to describe nationwide trends in lung surgery: incidence of surgical treatment, operative mortality, changes in surgical approaches, long term survival and predictors thereof in Finland between 2004 and 2014.

      Methods:
      Patients with any type of lung surgery and pre- or postoperative diagnosis of C34.* were identified from the national Care Register for Health Care which collects discharge data on all patients discharged from inpatient care as well as outpatients treated in specialized care. Patients were verified as lung cancer patients by linking data with diagnoses from the Finnish Cancer Registry. Mortality data were linked from Statistics Finland.

      Results:
      During the study period 3912 patients underwent lung surgery for cancer. Mean age was 66 years (SD 9.6), 62% were males. The number of operations increased over the years (p=0.02). Extent of surgery was pneumonectomy in 10%, lobectomy in 79.8% and sublobar resection in 10.2%. Women underwent sublobar resection more often than men (8.2% vs 13.5%, p<0.001). Overall 1 year survival was 85.5% and 5 -year survival was 51.4%. Age, stage of cancer, Charlson comorbidity index (CCI) and the proportion of lobectomy increased during the study period while survival remained stable.Predictors of mortality on multivariable regression were age, male gender, stage, CCI, pneumonectomy and adjuvant therapy.

      Conclusion:
      Despite a growing number of patients with increasing comorbidities treated surgically in a country with declining incidence of lung cancer and despite more advanced disease postoperative mortality for surgically resected lung cancer has remained stable. This suggests that modern surgical treatment could be offered more confidently to more patients with heavier disease burden.

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      P1.08-029 - Surgical Experience of Primary Salivary Gland Tumors of Lung: Experience from Tertiary Care Cancer Center in North India (ID 4992)

      14:30 - 15:45  |  Author(s): A. Jakhetiya, P.K. Garg, S.S. Deo, N.K. Shukla, D. Pandey, M. Ray, P. Malik, D. Jain, S. Kumar

      • Abstract
      • Slides

      Background:
      Primary salivary gland type tumors of lung (PSGTTL) are rare intra-thoracic malignant neoplasm. Their description in literature is largely limited to a few case series/case reports. We herewith present our surgical experience and review its clinical presentation, management options and survival outcomes.

      Methods:
      We performed a retrospective analysis of prospectively maintained computerized data-base of lung cancer patients at department of surgical oncology, Dr BRA-IRCH, AIIMS, Delhi. A total of nine patients underwent treatment for PSGTTL during the period from January 2012 to December 2015. Details concerning the clinical presentation, preoperative therapy, operative procedure, histopathological examination, postoperative complications and outcome were retrieved and analysed.

      Results:
      Median age of patients was 42 years (range 24-52 years) with male: female ratio of 7:2. Median duration of symptoms before presentation was 12 months (range 4-24 months). Most common symptoms were Hemoptysis (77%) and dyspnoea (66%). Fiber-optic bronchoscopy revealed endobronchial growth in all patients with six patients had growth in left main bronchus while one had growth in right main bronchus and two in right intermediate bronchus. Biopsy confirmed adenoid cystic carcinoma in 6 (66%) and muco-epidermoid carcinoma in 3 (33%) patients. Total seven patients underwent R‘0’ resection with pneumonectomy in five, bilobectomy in one, lower lobectomy in one patient. One patient developed pneumonia after left carinal pneumonectomy and succumbed to it. No major postoperative complication was encountered in remaining six patients. One patient refused surgery and one found unresectable in view of dense adhesions between lung and heart. Both patient received chemo-radiation and underwent bronchoscopic debulking and are in follow up. Median pathological tumor size was 3 cm. Median number of node harvested was 10 (range 4-18) however none showed metastasis. None of the operated patient developed relapse and overall eight patients are alive after a median follow up of 18 months.

      Conclusion:
      Primary salivary gland type tumors of lung (PSGTTL) are low grade malignancy and greater awareness of these tumors is necessary to avoid misdiagnosis and delay in treatment. Aggressive anatomical lung resection with preservation of functional lung parenchyma offers optimal outcome in such patients.

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      P1.08-030 - Female Lung Cancer and Our Five Year Experience (ID 4627)

      14:30 - 15:45  |  Author(s): F. Caushi, D. Xhemalaj, A. Hatibi, I. Skenduli, I. Bani, H. Hafizi, E. Shima, R. Kortoci

      • Abstract
      • Slides

      Background:
      Lung cancer is one of the leading causes of mortality in the world. The incidence of lung cancer in females is increasing, in contrast to that seen in males. However, according to a lot of publications, lung cancer is almost six times more frequent in men than in women. The literature shows clearly that lung cancer in women differs from that in men in several aspects and environmental factors and lifestyle plays an important role in the female lung carcinogenesis. The objectives of this study were to evaluate clinic-morphologic features of lung cancer in women and the role of the surgery in their treatment.

      Methods:
      This was a descriptive retrospective study, conducted for five years. We analyzed all patients hospitalized diagnosed and treated for lung cancer and using Pearson Chi-Square test.

      Results:
      The ratio men to women for patients diagnosed with lung cancer was 8 to1.The most common histotype was Adenocarcinoma 76%, Squamous cell carcinoma 11%, Small cell carcinoma 5%, others 8%.The average age was 57.5 with SD±12 years. 6% of females were in I stage, 22% of them were in II stage, 15% of them were in IIIA stage, 10% of them in IIIB stage and 47% in IV stage. Only 9% of our patients were smokers. Dyspnea was the main clinical sign, found in 67% of women. The standardized incidence of female lung cancer patients was 5/100.000. The surgery was performed in 20% of them meanwhile in men it was performed in 12.5% of cases.

      Conclusion:
      Most of women diagnosed with lung cancer were in advanced stages. Adenocarcinoma is the common histotype. This study shows that lung cancer in female is eight time less frequent in women than in men. Since the ratio men to women regarding to being operable is in the favor of women because they are diagnosed earlier comparing to men, women are more subject of surgery. Because the clinical signs of lung cancer are far from being specific, a substantial portion of lung cancer cases and deaths could be prevented by applying effective prevention measures, such as tobacco control and the use of early detection tests.

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      P1.08-031 - Non-Small Cell Lung Cancer in Patients Aged 40 Years or Younger: Clinical, Surgical, and Long-Term Outcomes (ID 6201)

      14:30 - 15:45  |  Author(s): D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari

      • Abstract

      Background:
      Non-small cell lung cancer (NSCLC) in young patients is uncommon and has clinical characteristics different from that in older patients. We report the outcomes of a single institutional experience in the treatment of young patients with NSCLC.

      Methods:
      Records of patients with NSCLC operated on between 1998 and 2013 were retrospectively analyzed from a prospective database.We identify two groups: G1 with patients resected with intention-to-treat, and G2 who underwent only diagnostic surgical procedures due to advanced NSCLC. There were 47 patients (27 in G1, 13 men; and 20 in G2, 10 men) with a median age of 37 years in G1 (range, 16-40) and 38 years in G2 (range, 24-40).Survival was calculated by using Kaplan-Meier method.

      Results:
      Induction treatment (IT) was administered in 17 patients in G1; no patient in G2 received IT. In G1, surgery included 3 wedges, 1 segmentectomy, 18 lobectomies, 5 pneumonectomies; in G2, surgery included 3 explorative thoracotomies, 8 nodal biopsies, and 6 pleural biopsies. Histological diagnosis was adenocarcinoma in all the patients. Median tumor size was 22 mm (range, 5-125) in G1. Postoperative staging in G1 included 11 stage I, 4 stage II, and 12 stage III; all patients in G2 were stage IV and none was alive at 5-year. Five-year overall survival and disease-free survival in G1 were 55% and 51%, respectively (median, 30 and 16 months, respectively). In G1 recurrence occurred in 12 patients most of them at extra-thoracic sites (9/12 [75%]). Factors associated with increased survival in G1 included IT (p=.0002) and right side disease (p=.01). At multivariate analysis in G1, IT [p=.03 (95% CI: 0.67-0.89)] influenced long-term survival.

      Conclusion:
      In our experience, all young patients had adenocarcinoma with a predominance of women. Patients receiving pulmonary resection for curative intent had the best prognosis and among these, those receiving IT had the best long-term survival.

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      P1.08-032 - Impact of the Oncogenic Status on the Mode of Recurrence in Resected Non-Small Cell Lung Cancer (ID 5392)

      14:30 - 15:45  |  Author(s): T. Mizuno, Y. Yatabe, S. Sakata, K. Seto, H. Dejima, H. Kuroda, N. Sakakura, Y. Sakao

      • Abstract
      • Slides

      Background:
      Surgical resection is employed in patients with resectable non-small cell lung cancer (NSCLC). Despite complete resection, recurrence is sometimes observed. Oncogenic mutations promote initiation and progression of lung cancer, and mutation status predicts treatment outcome of advanced NSCLC; however, their impact on the recurrence patterns remain poorly understood.

      Methods:
      We retrospectively studied 401 patients showing recurrence after complete resection of NSCLC. Clinicopathological factors were reviewed for time to recurrence (TTR), and recurrence patterns were compared according to oncogenic status and examined according to EGFR mutational subtype.

      Results:
      Among 401 patients, 185 with EGFR mutation, 46 with KRAS mutation, 15 with ALK rearrangement, and 155 with triple negative mutation (TN) were identified. Multivariate analysis following univariate analyses showed that younger age, well–moderately differentiated histology, earlier pathologic stage, and presence of EGFR or ALK mutation were favorable prognostic factors for TTR. Locoregional recurrence was observed in 53.3% of ALK-positive patients, being significantly common in these patients than in EGFR- and KRAS-positive patients. EGFR-positive patients mostly experienced pleural recurrence, the incidence of which was significantly higher in TN patients. Adrenal recurrence was observed in 7.2% of TN patients, but it was rarely identified in EGFR-positive patients. (Figure) Among EGFR-positive patients, the incidence of brain metastases was significantly higher in L858R cohort than in Del Ex19 cohort. Figure 1



      Conclusion:
      In resected NSCLC, younger age, well–moderately differentiated histology, earlier pathologic stage, and presence of EGFR or ALK mutation were favorable factors for TTR, and distinct recurrence patterns were revealed according to oncogenic mutation status and mutational EGFR subtype. Our results may provide suggestions for developing a strategy for follow-up and adjuvant therapies after resection.

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      P1.08-033 - Effect of EGFR Mutations on Survival in Patients following Surgical Resection of Lung Adenocarcinoma (ID 4938)

      14:30 - 15:45  |  Author(s): G.L. Laidlaw, R. Gao, K. Ayers, L. Backhus, M.F. Berry, J.B. Shrager

      • Abstract
      • Slides

      Background:
      While numerous trials have evaluated the effects of EGFR mutations on survival in patients undergoing treatment with tyrosine kinase inhibitors (TKIs), research on the influence of EGFR mutations in patients undergoing surgical resection as their primary intervention is limited and conflicting. We hypothesized that patients with resectable EGFR-mutant tumors have a better postoperative prognosis than those with wild-type (WT) tumors, as EGFR-mutant tumors often include an in-situ component that portends an improved prognosis. We further hypothesized that the two most common EGFR mutations may impact post-resection prognosis differentially.

      Methods:
      We carried out a single-center, retrospective study evaluating the influence of EGFR mutation status on progression-free (PFS) and overall survival (OS) after resection, adjusting for tumor stage and ethnicity. Kaplan-Meier plots and Cox proportional hazard models were used to generate crude and adjusted hazard ratios.

      Results:
      249 patients underwent lung adenocarcinoma resection and had mutational analysis and ≥1 year of follow-up at our institution between 2008-2015. These resections included 200 lobectomies, 12 segmentectomies, and 32 wedge resections. Ninety-three (37.3%) patients had EGFR-mutant tumors. Relative to WT tumors, EGFR-mutant tumors were more likely to exhibit well-differentiated (44.0% vs 29.0%, p=0.009) or lepidic (61.3% vs 36.5%, p <0.0001) histology, and trended towards presenting as pathologic stage IA/IB (p=0.082). EGFR mutation improved crude OS (HR 0.39, 95% CI 0.159-0.931, p=0.034), but this difference became nonsignificant when adjusted for tumor stage and ethnicity (OS HR 0.549, 95% CI 0.200-1.508, p=0.245). PFS did not differ between mutant and WT cohorts (adjusted HR 0.94, 95% CI 0.550-1.603, p=0.817). In comparing L858R and Exon 19, neither PFS (adjusted HR 0.91, 95% CI 0.350-2.379, p=0.851) nor OS (HR 0.88, HR 0.160-4.790, p=0.879) significantly differed. Lastly, sublobar resection did not interact with EGFR mutation presence to affect PFS (interaction p-value=0.735) or OS (interaction p-value=0.771).

      Conclusion:
      Patients with EGFR-mutant adenocarcinomas exhibit improved crude post-resection OS vs. those with WT tumors, but this difference disappears after adjustment for tumor stage and ethnicity. These findings appear attributable to EGFR-mutant tumors presenting at earlier stages. We hypothesize that this occurs because lepidic tumors spend a longer phase in stage I before developing a more aggressive phenotype. Our finding that EGFR mutation status does not interact with resection extent (sublobar vs. ≥ lobar) suggests that mutation status should not affect surgical planning prior to resection.

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      P1.08-034 - Prognostic Impact of EGFR Mutation in Patients with Surgically Resected Lung Adenocarcinoma; Analysis about Subtypes of EGFR Mutations (ID 6031)

      14:30 - 15:45  |  Author(s): Y. Kawaguchi, T. Okano, K.T. Imai, S. Maehara, J. Maeda, K. Yoshida, M. Hagiwara, M. Kakihana, N. Kajiwara, T. Ohira, N. Ikeda

      • Abstract

      Background:
      Epidermal growth factor receptor (EGFR) gene mutations have an important role for predicting the prognosis in advanced or recurrent lung cancer patients. However, the significance of EGFR mutation as a prognostic factor for survival after complete resection remains controversial. The aim of this study is to evaluate the impact of mutational status in patients with surgically resected lung adenocarcinoma.

      Methods:
      We retrospectively investigated the data of 414 patients (pts) with p-stage I-IIIA adenocarcinoma who underwent completely tumor resection in our hospital from 2009 to 2013. Overall survival (OS), disease-free survival (DFS) , and clinico-pathological factors affecting these factors were evaluated.

      Results:
      There were 202 males and 212 females (median age, 67 years). In total, 270 (65%), 66 (16%) and 78 pts (19%) had p-stageI, II and IIIA disease respectively. In all 210 pts (51%) with EGFR mutation were detected. Eighty-six pts (21%) had exon 19 deletion (19 del) and 113 pts (27%), exon 21 mutation (L858R). Among 414 pts, 131 pts (31%) had lung cancer recurrence. The median follow-up period was 38.6 months. p-stageI mutant/wild:145/125, II:24/42, and IIIA:41/37. The 3-year survival rates of p-I-II and IIIA mutant/wild were 96.8%/92.1% and 81.6%/61.8% respectively. The median survival time of p-stageIIIA mutant was 80.5 months, and those of others were not reached. The 3-year DFS of p-I-II and IIIA mutant/wild were 78.3%/69.2% and 27.1%/45.1%, respectively. There were no significant difference in OS and DFS at each p-stage despite the EGFR mutational status. Compared to the wild type, the p-IIIA mutant group had a poor DFS. conversely, compared to wild type, the p-I mutant group showed a favorable DFS. According to the subtypes of EGFR mutation, there were no significant differences among EGFR subtypes, but pts with 19del tended to have the worst DFS. In subgroup analysis of 131 pts with recurrence, 3-year survival rate of p-I-II and IIIA mutant/wild were 92.0%/75.8% and 80.8%/45.6% respectively. Pts with p-IIIA mutant showed significantly favorable OS than those of wild type (p=0.014) as well as with p-I-II wild type. Although OS was not significantly different among the subtypes of EGFR mutation, pts with 19del showed statistically better prognosis than shown by the wild type (p=0.038).

      Conclusion:
      EGFR status was an independent prognostic factor in pts with surgically resected lung adenocarcinoma. Particularly, EGFR exon 19 deletion might be the strongest predictive factor of poor DFS and good OS in resected lung adenocarcinoma.

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      P1.08-035 - Analysis of Post-Operative Recurrence in a Population with NSCLC Harboring an EGFR Mutation: A Single Institutional Retrospective Study (ID 6306)

      14:30 - 15:45  |  Author(s): H. Kosuke, I. Kentaro, W. Fumiaki, Y. Isao, M. Takao, S. Hideto, S. Yuta, S. Haruko, S. Tadashi, N. Yoichi, H. Osamu

      • Abstract
      • Slides

      Background:
      The post-operative recurrence in the patients resected EGFR mutated NSCLC was higher than wild-type, as previous reported. However, whether EGFR mutational status is prognostic factor or not had not been yet proven, and we assessed the background of the patients with surgically resected NSCLC harboring EGFR mutation and the post-operative clinical course.

      Methods:
      We reviewed all patients with EGFR mutated NSCLC who received surgical therapy for lung cancer between March 2007 and April 2016 at Matsusaka Municipal Hospital in order to assess post-operative recurrence and overall survival retrospectively. Survival curves of time to post-operative recurrence and overall survival were calculated using the Kaplan-Meier method and were compared using the log-rank test. Subgroup analyses were conducted to evaluate predictive factors for post-operative recurrence.

      Results:
      A total of 116 patients were enrolled. The median age was 72.5, ranging from 37-88 years of age. Of the total, 83 patients (71.6%) were female, and 90 patients had never smoked. All patients except one with squamous cell carcinoma were diagnosed pathologically with adenocarcinoma. Of the patients 41.9% were diagnosed with Ex19 deletion and 50.0% were diagnosed with Ex21 L858R. Median time to post-operative recurrence was 70.5 months for the entire population. Multivariate analysis revealed that age (p=0.008), subtype of EGFR mutation (p=0.034), and pathological stage (p=0.00033) were predictive factors for post-operative recurrence. Subgroup analysis revealed there was a significant difference in time to post-operative recurrence between patients over 75 y.o and those under 74 y.o even in the population who received a lobectomy. (p=0.031)

      Conclusion:
      Elderly patients, and those with the Ex21 L858R point mutation, had a tendency to relapse after surgical therapy among the EGFR mutated NSCLC population. The rate of post-operative recurrence in EGFR mutated patients tended to be higher compared to historical data. Because of differences with retrospective data and the small sample size, further investigations are warranted to confirm these results.

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      P1.08-036 - Thoracotomy and VATS-Surgery in Local Non-Small Cell Lung Cancer: Differences in Long-Term Health Related Quality of Life (ID 5298)

      14:30 - 15:45  |  Author(s): V. Rauma, S. Andersson, J. Räsänen, H. Sintonen, J. Salo, I. Ilonen

      • Abstract
      • Slides

      Background:
      Older and more fragile NSCLC patients are operated on through video-assisted thoracic surgery (VATS), compared to thoracotomy. In this study we compare the long-term health related quality of life (HRQoL) among early stage and locally advanced NSCLC patients between these two operative methods.

      Methods:
      687 NSCLC patients underwent lobectomy or segmentectomy in our clinic between January 2000 and January 2013, of these 430 were operated before July 2009 and 257 after this. HRQoL questionnaire 15D was sent to patients alive in June 2011 and February 2016 (min. 2 years from operation). After the exclusion of patients with clinically extensive disease (T4, N2 or M1), lacking data (n=5) or receiving neoadjuvant therapy, 345 (191+154) patients were included in the study.

      Results:
      289 (84%) patients answered, 155 from the first and 134 from the second period. Respectively, 42 and 68 respondents had had VATS. The two groups differed in the following features: thoracotomy group had on average more advanced clinical and pathological stage (26% vs 7% and 28% vs 16% stage II & III, respectively), younger age at operation (63.5 vs 66.8 years), and higher frequency of adjuvant therapy (18% vs 5%) (p<0.05 in each). The VATS group scored statistically (p<0.05) and clinically significantly lower on the dimensions Breathing (0.63 vs 0.70), Excretion (0.78 vs 0.85), Usual activities (0.75 vs 0.81), Mental function (0.83 vs 0.89), Depression (0.82 vs 0.88), Distress (0.82 vs 0.88), Vitality (0.76 vs 0.82), Sexual activity (0.72 vs 0.80) and on the 15D score representing overall HRQoL (0.81 vs 0.85) (Figure). Figure 1



      Conclusion:
      Even with less invasive surgical techniques, the older and more comorbid patients seem to have lower long-term HRQoL. This is contrary to previous results of short-term reports.

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      P1.08-037 - Thoracoscopic Segmentectomy of Pulmonary Nodules after Computed Tomography–Assisted Bronchoscopic Metallic Coil Marking (2nd Version) (ID 5603)

      14:30 - 15:45  |  Author(s): T. Miyoshi, H. Sumitomo, K. Uyama, N. Hino

      • Abstract
      • Slides

      Background:
      With advances in computed tomography (CT), small pulmonary lesions previously unseen on chest radiographs are being increasingly detected. Among lesions less than 10 mm in size, a considerable number of malignancies have been reported. To localize small and deeply situated pulmonary nodules during thoracoscopy with roentgenographic fluoroscopy, we developed a marking procedure that uses a metallic coil and a coin for thoracoscopic segmentectomy.

      Methods:
      Fifteen patients underwent video-assisted thoracoscopic surgery for removal of 16 pulmonary lesions between January 2011 and January 2016. There were 6 males and 9 females, with an average age of 68.3 years (range 54 to 78 years). Fluoroscopy-assisted thoracoscopic surgery after CT-assisted bronchoscopic metallic coil marking was performed using an ultrathin bronchoscope under bi-plain fluoroscopy viewing a coin on a patient’s chest wall. The coin was simulated a pulmonary lesion by the CT findings, and it was put on the patient's chest wall. During thoracoscopy, a C-arm-shaped roentgenographic fluoroscope was used to detect the radiopaque nodules. The nodule with coil markings was grasped with forceps and resected in segmentectomy under fluoroscopic and thoracoscopic guidance.

      Results:
      The marking procedure took 11 to 49 minutes from insertion to removal of the bronchoscope. There were no complications from the marking, and all 16 nodules were easily localized by means of thoracoscopy. The metallic coil showed the nodules on the fluoroscopic monitor, which aided in nodule manipulation. Nodules were completely resected under thoracoscopic guidance in segmentectomy. The pathologic diagnosis was primary adenocarcinoma in 10 nodules, pulmonary metastases in 3 nodules, an atypical adenomatous hyperplasia in 1 nodule, a hamartoma in 1 nodule and a nontuberculous mycobacteriosis in 1 nodule. One case of an adenocarcinoma in situ with an extensive two segments was performed a curative segmentectomy.

      Conclusion:
      In this study, CT-guided transbronchial metallic coil marking with an ultrathin bronchoscope with a coin on a patient’s chest wall under bi-plain fluoroscopy after CT-assisted stimulation was found to be feasible and safe. In our previous report, CT had been needed at least three times, but this method needed only twice CT scan. It might be a useful method not only for making a diagnosis but also for therapeutic resection in selected early lung cancers.

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      P1.08-038 - VATS Sub-Lobar Anatomical Pulmonary Resections: Indications and Outcomes in Thoracic Oncological Practice (ID 5815)

      14:30 - 15:45  |  Author(s): B. Thapa, K. Perera, R. Manser, S. Knight, T. John, S. Barnett

      • Abstract
      • Slides

      Background:
      In patients with limited pulmonary reserve, sub-lobar anatomic pulmonary resection (SLAPR) may have reduced perioperative morbidity and mortality and additionally may better preserve long-term pulmonary function compared to lobectomy. SLAPR may also mitigate the oncological deficiencies of wedge resection. However, the safety and oncological efficacy of video assisted thoracoscopic surgical (VATS) SLAPR has not been well described. We therefore audited our recent experience of VATS SLAPR to evaluate: indications, safety, and oncological outcomes.

      Methods:
      We retrospectively reviewed a prospectively maintained database to identify all consecutive patients who underwent planned VATS SLAPR with curative intent. Demographics, co-morbidities, indications and treatment outcomes were retrieved, with supplemental chart review where necessary.

      Results:
      Seventy seven VATS SLAPRs were performed between December 2010 and May 2016. Median age of patients was 67 (44-83) years and 57% (44/77) were male. The majority (47/77; 61%) of SLAPRs were undertaken for resection of NSCLC. Indications for SLAPR in NSCLC patients included: inadequate pulmonary reserve (DLCO <60% or predicted post-operative DLCO <40%) in 21/47 (44%), excessive (≥2 major) comorbidities in 18/47 (38%), advanced age (≥75 years) in 13/47 (27%) or a combination of these factors precluding lobectomy. In patients with metastatic 22(28%) and benign 8(10%) nodules, indications included proximity to vascular structures or inability to palpate lesion precluding simple wedge resections. Superior segmentectomy (22/77; 28%) and lingula sparing left upper lobectomy (17/77; 22%) were the commonest SLAPRs performed. Seventy one (92%) were completed via VATS. Emergency conversion occurred in one case. Morbidity rate was 30% (23/77) and 30 day mortality rate was 2.5% (2/77). Pre-operative DLCO was not associated with post-operative pulmonary complication (P=0.7) or length of hospital stay (P=0.20). In the NSCLC sub group, all patients were clinically stage I; R0 resection was achieved in 100%. Median of 12(4-27) nodes were excised with a nodal upstaging rate of 25% (12/47) and pathological stage was I in 65%. Median disease free survival (DFS) was 40 months and median overall survival (OS) was not reached. Loco regional recurrence rate was zero. Pre-operative DLCO dichotomised using median did not correlate with OS (P=0.8) or DFS (P=0.29).

      Conclusion:
      A variety of VATS SLAPRs may be performed safely with acceptable morbidity and mortality in high risk patients. Complete microscopic resection and adequate nodal dissection can be achieved. Although larger studies and longer follow is needed, our findings suggest that VATS SLAPR achieves comparable oncological outcomes in high risk patients to formal lobectomy.

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      P1.08-039 - Systematic Review and Updated Meta-Analysis of Uniportal versus Multiportal Video-Assisted Thoracoscopic Surgery for Lung Cancer (ID 4951)

      14:30 - 15:45  |  Author(s): M. Kowalewski, M. Dancewicz, M. Bella, T.J. Szczęsny, P. Bławat, M.A. Lewandowska, A. Chrzastek, J. Kowalewski

      • Abstract

      Background:
      Uniportal video-assisted thoracoscopic surgery (VATS) is a challenging surgical procedure that poses substantial technical difficulties compared to multiportal VATS but has been associated with favorable outcomes in studies reported to date.

      Methods:
      On-line databases were screened until June 2016. Meta-analysis aimed to compare clinical outcomes of uniportal and multiportal VATS lobectomy for patients with lung cancer. Endpoints assessed included perioperative mortality, operative time and blood loss; length of hospital stay; duration of postoperative drainage; rates of conversion to open thoracotomy; number of harvested lymph nodes and overall morbidity. Risk Ratios (RR)/Mean Difference (MD) and corresponding 95% Confidence Intervals (95%CIs) served as primary statistics.

      Results:
      Twelve studies were included (among them 1 randomized trial) that enrolled N=2,476 patients. There was no difference in the 30-day mortality: (N=2,476); RR (95%CIs) 0.32 (0.03-3.01); p=0.32; Event rates: 0.10% (1/1,021) vs 0.07% (1/1,455); no difference were demonstrated for conversion-to-thoracotomy: 0.91 (0.48-1.73); p=0.77; similarly there were no differences in regard to operative times: MD (95%CIs): 3.50 ([-12.35]-19.34) min; p=0.67 and blood loss: -2.15 ([-17.13]-12.83) ml; p=0.78. There was no statistically significant difference between number of harvested lymph nodes: 18.4±6.6 vs 19.4±8.5; MD (95%CIs): -0.34 ([-1.39]-0.70) node; p=0.52. Uniportal VATS was associated with significantly shorter duration of chest tube drainage: -0.61 ([-0.99]-[-0.23]) days; p=0.002 (Figure 1A); and length of hospital stay: -0.58 ([-0.77]-[-0.40]) days; p<0.001 (Figure 1B). Overall morbidity was significantly reduced with uniportal VATS as well: RR (95%CIs) 0.77 (0.63-0.95); p=0.01. Figure 1 Figure 1. Individual and summary point estimates. Uniportal vs multiportal VATS. Length of hospital stay (A) and duration of chest tube drainage (B).



      Conclusion:
      Uniportal VATS is at least as safe and effective as multiportal VATS for patients with lung cancer. Whether clear postoperative benefits with uniportal VATS further translate into reduction of clinical endpoints and potentially improved survival remains to be confirmed in adequately powered randomized trial.

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      P1.08-040 - Lymph Node Sampling in 3-Port Video Assisted Thoracoscopic Surgery (VATS) vs Uniportal VATS (ID 5083)

      14:30 - 15:45  |  Author(s): C.H. Yi, S. Avtaar Singh, P. Lang, A. Gardiner, A. Kirk, M. Klimatsidas

      • Abstract
      • Slides

      Background:
      VATS is fast overtaking thoracotomy as the approach to lobectomies due to faster recovery times. Uniportal VATS lobectomies are slowly becoming more popular throughout the world but the advantages of Uniportal VATS over the standard 3-port approach is unclear. The lung resection can often be performed via a Uniportal approach although concurrent lymphadenectomy/lymph node sampling, may be more challenging. We explored the adequacy of lymph node sampling at our unit as per the ESTS 2006 guidelines on intraoperative lymph node staging.

      Methods:
      All Primary Lung cancers (Non-small cell lung cancers) performed by 4 VATS surgeons from May 2015-July 2016 were included in the study. A single surgeon performed all the Uniportal VATS lobectomies. The standard 3-port approach was employed by 4 VATS surgeons. Patient demographic details and length of stay were obtained from our Cardiothoracic Database (CaTHi) alongside pathological findings.

      Results:
      Figure 1 The patients in the standard cohort had a higher ThoracoScore indicating increased risk of surgery. There was no statistically significant demographic difference between the two groups. The rate of lymph node dissection was similar in both groups.



      Conclusion:
      Despite the perceived limited access, uniportal VATS has shown to be as good as standard 3 port VATS for lymph node sampling intraoperatively.

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      P1.08-041 - Disease Free and Overall Survival is Equal in Open and VATS Resection for Early Lung Cancer in a Multivariate Analysis (ID 4644)

      14:30 - 15:45  |  Author(s): C. Ng, F. Kocher, H. Maier, M. Sacher, G. Laimer, M. Fiegl, P. Lucciarini, T. Schmid, F. Augustin

      • Abstract

      Background:
      Video-assisted thoracic surgery (VATS) has become a valid alternative to open resection for lung cancer treatment. However, robust data on the oncologic equality are still missing. This study evaluates disease free and overall survival for patients with early stage (cN0) lung cancer treated either with open or VATS resection.

      Methods:
      A total of 359 patients with early stage (cN0) lung cancer with available survival data in our institutional database were treated between 2004 and 2015. VATS was introduced in 2009, since that time all clinically nodal negative patients were treated with an intended VATS approach.

      Results:
      There were 198 male patients; median age was 65 (range 38-85) years. 256 (71.3%) patients were treated with a minimally invasive approach. There were significantly more female patients (p=0.002) and lower pT-stages (p=0.002) in the VATS group. Nodal upstaging was found in 19.1% in the VATS group and 23.3% in the open group (p=0.486). 5-year disease free survival was 61.2% in the VATS group and 63.8% in the open group (p=0.492). 5-year overall survival was 84.3% in the VATS group and 73.3% in the open group (p=0.139), Figure 1. In a multivariate analysis including age, gender, pT-status, pN-status and surgical approach, none of the factors proofed to independently predict disease free survival. In overall survival, a positive pN status was found to be the only independent negative prognostic factor (HR: 2.2, 95% CI: 1.2-4.1). Figure 1



      Conclusion:
      Overall and disease free survival are not influenced by the type of surgical approach. Due to perioperative benefits with shorter length of hospital stay and less complications, a minimally invasive approach as the gold standard of surgical treatment for clinically nodal negative lung cancer patients should be advocated.

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      P1.08-042 - Overall Survival and Tumor Recurrence after VATS Lobectomy of N1 Positive NSCLC is Equal to Open Resection (ID 4721)

      14:30 - 15:45  |  Author(s): H. Maier, C. Ng, F. Kocher, M. Sacher, G. Laimer, P. Lucciarini, T. Schmid, F. Augustin

      • Abstract
      • Slides

      Background:
      Video-assisted thoracoscopic surgery (VATS) is an accepted alternative to open resection for early stage non-small cell lung cancer. This study was performed to analyze survival after primary VATS anatomic resection for nodal positive NSCLC compared to an open approach.

      Methods:
      The prospective institutional VATS database was searched for pN1 patients after primary surgery for NSCLC (62/504 patients between February 2009 and December 2015). Exclusion criteria were neoadjuvant treatment and conversion to thoracotomy. Demographics and survival were compared to a historic group of N1 positive patients, who underwent primary open surgery via a standard posterolateral thoracotomy for lung cancer between 2002 and 2007 (57 patients).

      Results:
      Age (65 vs 61.5 years), gender and stage distribution (UICC IIA vs >IIA) did not differ between the VATS and open group. Half of the patients in the VATS group had clinical stage N0 (31/62) confirmed by PET-CT. More people received adjuvant therapy after VATS lobectomy (50/62 vs 31/57, p=0.003). Median follow up was 22 months in the VATS group and 47 months in the open group (p<0.0001). Disease recurrence occurred in 16/62 and 22/57 patients after a median of 13 and 12 months, respectively, (p=0.1692). Overall survival did not differ between the two groups (Figure 1, log rank, p=0.4006). No survival difference was found between unforeseen and clinically evident nodal positive patients in the VATS group (p=0.9686). Figure 1



      Conclusion:
      VATS lobectomy in nodal positive lung cancer patients is oncologically equal to open resection with similar survival and recurrence rates. Half of the lymph node metastases have been missed by clinical staging. Interestingly, the higher rate of patients receiving adjuvant chemotherapy after VATS lobectomy did not result in significant better survival.

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      P1.08-043 - Perioperative and Mid-Term Outcomes after Single Port versus Multi-Ports Thoracoscopic Lobectomy for Lung Cancer: A Propensity Matching Study (ID 6366)

      14:30 - 15:45  |  Author(s): B.S. Son, D.H. Kim

      • Abstract
      • Slides

      Background:
      Recently, single incision thoracoscopic lobectomy for non-small cell lung cancer has been performed at several centers worldwide. But compared with conventional multi-ports thoracoscopic lobectomy, Reports for perioperative and oncologic outcomes after single incision thoracosopic lobectomy are limited. This study aimed to compare single incision thoracoscopic lobectomy against conventional multi-ports thoracoscopic lobectomy for non-small cell lung cancer.

      Methods:
      Between January 2009 and December 2016, 141 single-incision thoracoscopic lobectomies and 159 multi-ports thoracoscopic lobectomies were enrolled on patients with non-small cell lung cancer in our institute. Preoperative patient characteristics including gender, age, smoking history (P/Y), comorbidities, histologic type, tumor size, pathological stage, histology and forced expiratory volume in 1 s (FEV1) and pathologic stage were compared between two groups. Age and previous caner history were used for propensity matching because age and previous caner history were a statistically significant difference among parameters. After propensity score matching, 141 single incision thoracoscopic lobectomies and 141 multi-ports thoracoscopic lobectomies were selected and compared.

      Results:
      There were no differences significantly between single incision and multi-ports thoracoscopic lobectomy with regard to operation time (233.3 ± 70.8 vs. 222.7 ± 79.5, P=0.236), hospital stay (15.6 ± 31.8 vs. 21.3 ± 114.4, P=0.572), number of lymph node (23.6 ± 11.6 vs. 25.5 ± 12.9, P=0.209), the number of units transfused pack RBC (0.3±0.7 vs. 0.5±1.4, P=0.055), FFP (0.0 ± 0.3 vs. 0.1 ± 0.8, P=0.145) and PLT(0.1 ± 1.5 vs. 0.1 ± 1.1, P>0.05) during perioperative period. Overall survival rate and disease free survival also were no difference between two groups. Chest tube drainage for 24 hours after operation (410.2 ± 205.6ml vs. 571.0 ± 289.3ml, P<0.01) and intraoperative blood loss (314.6 ± 348.6ml vs. 555.0 ± 460.5ml, P<0.01) are better with single incision thoracoscopic lobectomy group.

      Conclusion:
      Single incision thoracoscopic lobectomy could achieve similar short-term surgical results and mid-term outcomes compared with multi-ports thorscoscopic lobectomy except

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      P1.08-044 - Comparison of Peri-Operative Outcomes after Robotic-Assisted Video-Thoracoscopic Lobectomies versus Segmentectomies (ID 5259)

      14:30 - 15:45  |  Author(s): M.F. Echavarria, A. Cheng, F. Velez, E. Ng, C. Moodie, J. Garrett, J. Fontaine, E.M. Toloza

      • Abstract
      • Slides

      Background:
      Lobectomy is the standard procedure for early stage lung cancer. The role of sub-lobar resection is currently under investigation. Published comparisons between VATS, R-VATS, and open lobectomy vs. segmentectomy have been reported. The goal of our study was to compare peri-operative outcomes after R-VATS lobectomy vs segmentectomy. Comparison between these two procedures using robotic instruments has not been published.

      Methods:
      We retrospectively analyzed prospectively collected data from 253 consecutive patients who underwent lobectomy(N=208) and segmentectomy(N=45) via R-VATS performed by one surgeon. Unpaired Student’s t-test and Chi-square test were used to determine statistical significance(p≤ 0.05) of intra- and post-operative outcomes between these 2 groups.

      Results:
      Figure 1Figure 2 No significant difference was found on intra-operative complications (18/208 vs. 4/43; p=0.70). However, the mean duration of R-VATS segmentectomy was longer than lobectomy(258min vs. 207.5min: p<0.01). Total post-operative complications didn't differ between the groups(24/43 vs. 84/208; p=0.071). Individual complications reviewed included cardiovascular, wound infections, and respiratory adverse outcomes. Only pneumothorax after chest tube removal(p=0.032) and effusion/empyema(p=0.011) requiring intervention were significant.





      Conclusion:
      R-VATS segmentectomy on average take longer and has more postoperative complications which can be explained by patients' underlying pulmonary disease. R-VATS segmentectomy may be considered as an alternative procedure to R-VATS lobectomy in order to conserve lung function.

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      P1.08-045 - Partial Lung Resection after Bronchoscopic Metallic Coil Marking Using Two Coins and C-Armed Shaped Fluoroscopic Guidance (ID 5837)

      14:30 - 15:45  |  Author(s): K. Uyama, T. Miyoshi, H. Sumitomo, N. Hino

      • Abstract
      • Slides

      Background:
      The opportunities detecting small pulmonary lesions are increasing because of the spread of CT screening, however, it is sometimes hard to localize the non-palpable tumors located in deep part of the lungs or showing grand- glass opacity lesions. Therefore, it is necessary to mark the location of these tumors before operation. We developed the simple and easy marking technique using two coins and a metallic coil, and examined its reliability, safety, and usefulness.

      Methods:
      23 patients with 24 small peripheral pulmonary lesions less than 20 mm in size underwent fluoroscopy-assisted thoracoscopic partial lung resection after bronchoscopic metallic coil marking using two coins and C-armed shaped fluoroscopic guidance. The average diameter of the lesions was 10.33mm, and the average distance from the pleural surface was 8.37mm. At first we conducted chest CT scan and confirmed the number of the CT slice in which the tumor exist. Two coins were put on the patient’s chest wall according with the slice number of the antecedent CT scan. A metallic coil was installed in the bronchus near the lesion where the shadows of two coins overlap using ultrathin bronchoscopy under C-armed shaped fluoroscopic guidance. Afterwards, we performed wide wedge resection of the nodules with coil marking under fluoroscopic and thoracoscopic guidance.

      Results:
      We could install coils in the objective bronchi in all cases. The marking procedure took 13 to 39 minutes from insertion to removal of the bronchoscope. There were no complications from the marking, and all 24 nodules were easily localized at the time of VATS resection. The pathologic diagnosis was primary adenocarcinoma in 9 nodules, pulmonary metastases in 8 nodules, a primary squamous carcinoma in 2 nodules, small cell carcinoma in 2 nodules, an atypical adenomatous hyperplasia in 1 nodule, and a nontuberculous mycobacteriosis in 1 nodule.

      Conclusion:
      The fluoroscopy-guided coil marking using ultrathin bronchoscope with two coins on a patient’s chest wall after CT-assisted stimulation was a safe, convenient, and reliable method for localization of small pulmonary lesions before VATS partial resection.

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      P1.08-046 - Survival Following Thoracoscopic Pulmonary Metastasectomy for Osteosarcoma (ID 5893)

      14:30 - 15:45  |  Author(s): T. Tojo, T. Kawaguchi, M. Yasukawa, N. Kawai, S. Taniguchi

      • Abstract

      Background:
      Osteosarcoma is the malignant primary bone tumors which often develop in young people, 5-year overall survival in patients with pulmonary metastasis is around 50%. The objective of this study was to report the overall survival in a group of patients with metastatic osteosarcoma treated with surgical removal of the lung metastases.

      Methods:
      A retrospectic review from our data base revealed 9 patients performing 18 pulmonary metastasectomies between August 2005 and May 2016. The mean age was 18 years (range, 15-24) and 5 patients were male. All patients were treated with chemotherapy and oncologic resection of the primary tumor and thoracoscopic surgical removal of the lung metastases. 4 patients had bilateral lung operations, and only one lung metastasis was resected in three cases and the median number of metastases resected was 1.94.

      Results:
      The median overall survival was 34.9 months (range, 10-129). At follow up, 4 patients were dead with a median follow-up of 21.9 months. 5 patients were alive, and 4 patients were disease-free survivors, and 2 of 4 patients had only one pulmonary metastasis at the first lung matstasectomy.

      Conclusion:
      In selected patients, thoracoscopically pulmonary metastasectomy for osteosarcoma is safe, and may confer a good survival. Recurrent metastasis after resection confers a good prognosis.

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      P1.08-047 - Decreasing Use of Epidural Analgesia with Increasing Minimally Invasive Lobectomy: Impact on Postoperative Morbidity (ID 4941)

      14:30 - 15:45  |  Author(s): M. Zeltsman, A. Poch, T. Eguchi, S. Bains, B.J. Park, D. Jones, P.S. Adusumilli

      • Abstract
      • Slides

      Background:
      The goal of this study is to assess the impact of the decreasing use of epidural analgesia (infusion ≥24 hours) on the incidence of postoperative morbidity following minimally invasive surgical (MIS; includes VATS and robotic-assisted) lobectomy in patients with non-small cell lung cancer (NSCLC).

      Methods:
      We reviewed 1206 patients who underwent MIS lobectomy for pathological stage I-III NSCLC in 2009-10 (n=506) and 2014-15 (n=700) at our institution. Clinical data was obtained from a prospectively maintained database and by review of individual patient medical records. Patients with induction therapy (n=225) or conversion from MIS to thoracotomy (n=99) were excluded. Postoperative morbidity (≤30 days) was graded based on the Common Terminology Criteria for Adverse Events (CTCAE). Statistical comparison was performed using Chi-squared analysis and Fisher’s exact test.

      Results:
      A total of 884 patients were included in this study (2009-10, n=401; 2014-15, n=483). The rate of MIS lobectomy significantly increased in 2014-15 compared to 2009-10 (74% vs. 53%, p<0.001) with a simultaneous decrease in the use of epidural analgesia (92.9% vs. 53.6%, p<0.001; Figure 1A and 1B). In the MIS group, there was no difference in age, sex, or pathological stage between the 2009-10 and 2014-15 cohorts. There was no significant change in the incidence of any, severe respiratory or cardiovascular morbidity (CTCAE grade ≥3) following MIS lobectomy between the two time periods evaluated (Figure 1C). However, the incidence of CTCAE grade ≥2 respiratory morbidity in 2014-15 was higher than that in 2009-10 (7.1% vs. 12.6%, p=0.047).Figure 1



      Conclusion:
      In our study cohort, the observed decrease in use of epidural analgesia with the increasing rate of MIS lobectomy did not affect the incidence of severe postoperative morbidity.

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      P1.08-048 - Comparison of Pulmonary Function after Robotic-Assisted Video-Thoracoscopic Lobectomies vs Segmentectomies (ID 5258)

      14:30 - 15:45  |  Author(s): M.F. Echavarria, A. Cheng, F. Velez, E. Ng, C. Moodie, J. Garrett, J. Fontaine, E.M. Toloza

      • Abstract
      • Slides

      Background:
      Lobectomy is the standard surgical procedure for early stage lung cancer, but sub-lobar resection is being debated. We compared pulmonary function after robotic-assisted video-assisted Thoracoscopic (R-VATS) segmentectomy versus lobectomy; comparison using robotic instruments hasn't been published.

      Methods:
      We retrospectively analyzed prospectively collected data from 251 consecutive patients who underwent lobectomy (N=208) and segmentectomy (N=43) via R-VATS by one surgeon. Unpaired Student's t-test and Chi-square tests were used to determine statistical significance(p≤ 0.05). Majority of patients had no prior lung surgery. We used “Predicted(PFT)=Preop(PFT)x(1-(Segments x 0.0556))”, where 0.0556=1seg/18seg. For patients with prior resections, the number of segments previously resected was taken into account(1seg/(18-Prior resection)).

      Results:
      Figure 1Figure 2Preoperative FEV1(%) and DLCO(%) were statistically significant between the two groups. Also, FEV1 and DLCO were lower in segmentectomy patients. As expected, predicted changes between preoperative and postoperative values were significant. Predicted post-operative FEV1 and DLCO did not show any significant difference between the two groups.





      Conclusion:
      While pre-operative PFTs were significantly lower in segmentectomy patients compared to lobectomy patients, predicted post-operative PFTs do not differ significantly. Predicted changes for FEV1 and DLCO are significantly less in segmentectomy. Thus, negate the difference in pre-operative PFTs. In conclusion, R-VATS segmentectomy preserves lung function and may be considered a viable alternative

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      P1.08-049 - CT Guided Labeling with Indocyanine Green of Small Lung Nodules for Sublobar Resection Utilizing Robotic Assisted Thorascopic Surgery (RATS) (ID 4298)

      14:30 - 15:45  |  Author(s): K.A. Lee, L. Fox, A. Hall, V. Turiano

      • Abstract
      • Slides

      Background:
      Localization of deep and small pulmonary lung nodules undergoing a wedge or sublobar resection may be challenging during thoracoscopy, and may necessitate greater resection or conversion to thoracotomy. Particularly in robotic surgery, with the absence of tactile feedback. Percutaneous CT guided Indocyanine Green injection provides a means to pinpoint these nodules.

      Methods:
      A retrospective study of 40 consecutive patients who underwent preoperative CT-guided localization of solitary pulmonary nodules with ICG. Nodules < 15mm were 21/40 (52.5%), < 20mm 30/40 (75%), and < 30mm 38/40 (95%). A 22-gauge spinal needle (BD, NJ) or Chiba needle (Cook, IA) was positioned into or adjacent to the nodule. 0.4cc Indocyanine Green was injected and the inner stylet withdrawn. The Xi daVinci robot (Intuitive Surgery, CA) was docked and the firefly filter of the 8mm camera was activated, and the nodule illuminates in a flouresence green color. A wedge or sublobar resection was performed, with progression to lobectomy when indicated.

      Results:
      CT guidance successfully localized the nodules in 100% of 40 patients employing this technique. Success was measured in nodule illumination as seen by the surgeon upon activation of the camera filter and confirmed on frozen and permanent section by pathology. Initial wedge resection for diagnosis prior to lobectomy and sublobar resection for decreased PFTs or decrease cardiac function were performed by Robotic Assisted Thoracoscopy (RATS). There were no conversions to thoracotomy. Diagnosis were adenocarcinoma in 18 patients (45%), squamous cell carcinoma in 7 patients (17.5%), carcinoid in 1 patient (2.5%), metastatic in 8 patients (20%), and benign in 6 patients (15%). There were no 30 or 90 day mortalities. A chest tube reinsertion in one patient for pneumothorax. Economically the cost for the vial of ICG is $79.56 compared to a fiducil marker at a cost of $128.00. Thoracic Surgery has access to CT scanners, without an extra cost, electromagnetic navigation systems come with significant added costs.

      Conclusion:
      Percutaneous CT guided labeling with ICG is quick and economical for the localization of small and deep nodules undergoing RATS wedge or sublobar resection. This technique may be supportive in preserving lung parenchyma and reduce the need for conversion to thoracotomy, maintaining minimal invasive thoracic surgery, especially where palpation or tactile feedback is absent.

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      P1.08-050 - VATS Lobectomy in Locally Advanced NSCLC: A Single Centre Experience (ID 4793)

      14:30 - 15:45  |  Author(s): D. Tosi, L. Rosso, P. Mendogni, A. Palleschi, I. Righi, M. Montoli, F. Damarco, M. Nosotti

      • Abstract

      Background:
      VATS lobectomy has become the gold standard in early stage lung cancer treatment, but its role is still debated in case of locally advanced disease (tumor larger than 5 cm, chest wall involvement, hilar adenopathy, need for sleeve resection). The aim of this study was to evaluate the main differences between VATS lobectomy performed for early stage NSCLC and the ones performed for locally advanced disease.

      Methods:
      We retrospectively analyzed patients that underwent VATS lobectomy for tumor resection in our centre, from July 2011 till December 2015. Patients included in the study were similar for demographic characteristics and for number of resected lymph nodes. We performed 136 VATS lobectomies: 124 following standard indications (group A); 12 following “extended” indications (group B). Group B is composed by: 3 VATS sleeve lobectomy; 3 VATS lobectomy followed by limited chest wall resection (hybrid technique); 6 VATS lobectomy for NSCLC larger than 5cm. We evaluated the conversion rate to open surgery, the intraoperative blood loss, the operation lenght, the chest drain maintenance and the length of hospitalization.

      Results:
      Intra-operative conversion rate was higher in group A than in Group B, but not statistically different (13,7% vs 9%; p>0,05). No differences were detected in the intraoperative blood loss. Instead we observed differences in terms of operation length, of chest drain maintenance (4,8 vs 7,4 days; p<0,05) and of length of hospitalization (6,2 vs 10,3 days; p<0,05).

      Conclusion:
      We believe that VATS lobectomy can be proposed even in “complex cases”. Minimal invasive approach didn’t increase the intraoperative blood loss and didn’t imply a significant impact in terms of intraoperative conversion to open surgery. We detected differences in the operation length and in chest drain maintenance. Other studies with an higher population of “complex cases” are needed, but we are trustful that VATS lobectomy indications will be extended in the short term.

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      P1.08-051 - VATS Lobectomy Combined with Limited Thoracotomy for Treatment of Superior Sulcus Tumors (ID 5195)

      14:30 - 15:45  |  Author(s): D. Tosi, L. Rosso, A. Palleschi, P. Mendogni, I. Righi, M. Montoli, C. Bareggi, M. Nosotti

      • Abstract

      Background:
      Despite the increasing of VATS procedures even for locally advanced NSCLC, Pancoast tumors have been rarely approached with VATS combined with chest wall resection. This report describes an hybrid surgical technique to approach "en block" chest resection and pulmonary lobectomy for superior sulcus tumors

      Methods:
      We present two cases of patients referred to our Institution. A female patient affected by right anterior Pancoast tumor surgically staged as cT4N0M0 for suspected anonymous vein invasion, underwent induction therapy with four cycles of cisplatin and Pemetrexed plus 60 Gy irradiation, with satisfactory tumor reduction. The surgical operation comprised an initial VATS approach to the hilar structures followed by a limited C-shaped anterior contra-incision; finally, the right upper lobe "en block" with the anterior part of the first and second rib was removed. The second case is a 57-year-old man, affected by a cT3N0M0 posterior Pancoast tumor, treated with induction chemoradiotherapy prior to the hybrid surgical approach. After thoracoscopic pleural cavity inspection, an upper right VATS lobectomy by a 3-port standard approach was performed. The chest wall was resected through a limited paravertebral incision, allowing the extraction of the lobe together with the rib segments. The posterior chest wall defect was repaired with a synthetic patch.

      Results:
      The postoperative period was uneventful in both cases, and the pain never exceed a score of 4 on a visual analogue scale. The patients were discharged respectively 9 and 11 days after surgery. Pathological results revealed in both cases nonvital tumor cells in the specimen (ypT0N0M0). The patients are free from disease and post-thoracotomy syndrome at 14 and 18 months' follow-up

      Conclusion:
      VATS combined with thoracotomy approach leads to asses with precision the thoracic wall resection and reduce surgical trauma with very good results in term of postoperative morbidity. We strongly support the “VATS observation first” philosophy, to exclude previously undetected pleural dissemination and to precisely define the tumor location. Further experiences are needed to validate the role of VATS lobectomy in the multidisciplinary management of Pancoast tumor

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      P1.08-052 - Comparison Study of Perioperative Outcomes in Robotic, Video-Assisted Thoracic Surgery, and Thoracotomy Approaches for Lung Cancer (ID 5341)

      14:30 - 15:45  |  Author(s): H. Nakamura, Y. Taniguchi, K. Miwa, K. Araki, T. Haruki, M. Wakahara, Y. Yurugi, Y. Kubouchi, Y. Kidokoro, T. Ono

      • Abstract

      Background:
      Robotic surgery for lung cancer has not widely spread because of the lack of definitive advantage compared to conventional approaches, specifically video-assisted thoracic surgery (VATS). Some studies have reported that postoperative complication in robotic surgery is superior for unclear reasons. The aim of this study is to compare the perioperative outcomes, particularly pointing out postoperative complication among robotic, video-assisted thoracic surgery (VATS) and thoracotomy approach in non-small cell lung cancer (NSCLC).

      Methods:
      We performed a retrospective review of NSCLC patients who underwent curative anatomical resection in our hospital from January 2011 to April 2016. There were 346 lobectomy cases and 76 segmentectomy cases. The patients were classified into four groups (robotic, VATS, open conversion from VATS, and thoracotomy) and were compared for differences in perioperative outcomes.

      Results:
      Total 422 patients (43 robotic, 265 VATS, 30 open conversion from VATS, and 84 thoracotomy) were included in the analysis. Clinical and pathological stage showed earlier in robotic and VATS cases. Operative time (min), bleeding amount (gram) and drainage period (days) for robot, VATS, conversion and thoracotomy were 247/20/2, 188/10/2, 246/100/2, 225/ 92.5/2 respectively(p<0.0001). In the incidence of all, over G3, respiratory over G3 postoperative complications robotic surgery showed significantly lowest among them and there were neither conversion to thoracotomy nor operative/hospital mortality in robotic surgery.

      Conclusion:
      In our initial results of robotic surgery, lower incidence of operative morbidities is one of the advantageous features. Important issue whether robotic surgery is established as a minimally invasive approach for NSCLC or not should be verified.

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      P1.08-053 - Thoracoscopic Partial Resection for Peripheral Pulmonary Nodules without Using Stapler (ID 3700)

      14:30 - 15:45  |  Author(s): T. Toyazaki, T. Nakagawa, Y. Tomioka, Y. Ueda, M. Gotoh

      • Abstract
      • Slides

      Background:
      Advances in radiologic studies, such as high resolution computed tomography (HRCT), have enabled frequent detection of small lung nodules. Accordingly, opportunity for sublobar resections for small lesions has increased. Recently, we have introduced thoracoscopic partial resection for peripheral pulmonary small nodules without using stapler to reduce the cost of operation.

      Methods:
      After detecting the peripheral nodules, partial resection was performed with electrocautery and two different methods of surface sealing were followed. Coagulation method (C method) with SOFT COAG alone and Coagulation-suturing method (CS method) with SOFT COAG combined with continuous suturing by an absorbable barbed suture. The clinical outcome of the two methods was retrospectively compared in this study.

      Results:
      C method was performed in 19 lesions of 18 cases and CS method was performed in 17 lesions of 16 cases. Primary lung cancer was most frequent as 19 lesions of 18 cases. There was no significant difference between the two groups in size and depth of the lesions. Operation time was significantly longer in CS method than in C method. Postoperative air leakage was complicated to 4 cases in C method and one of them needed re-do surgery, whereas only one case in CS method had temporary air leakage. Postoperative computed tomography revealed cavitation in 3 cases of C method and in 4 cases of CS method all without related symptoms. There was no local recurrence in resected sites.

      Conclusion:
      C method was technically easy to perform, but air leakage may be possibly prolonged after surgery. CS method may have an advantage of less air leakage than C method, but technical learning is important to shorten operation time.

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      P1.08-054 - Uniportal VATS Lobectomy in the Treatment of NSCLC (ID 3709)

      14:30 - 15:45  |  Author(s): N. Ilic, J. Juricic, D. Krnic, D. Orsulic, I. Simundza, M. Urlic, N. Frleta Ilic, D. Ilic

      • Abstract
      • Slides

      Background:
      Uniportal Video-Assisted Thoracic Surgery (uniportal VATS) lobectomy represents the pinnacle of evolution for minimally invasive techniques in surgical management of lung cancer. Growing evidence suggest that Uniportal VATS procedures are technically feasible and safe with immediate outcomes comparable to traditional VATS approach. Uniportal approach has demonstrated equivalent disease-free survival, at intermediate follow-up for patients with early stage NSCLC, compared to conventional VATS. It represents a less invasive approach, and offers the advantage of minimizing the extent of the surgical access trauma thus resulting in postoperative pain reduction, muffled inflammatory response, early recovery and better cosmesis. Some authors described minimal changes in pulmonary function after uniportal surgery in patients with poor cardio-respiratory function. Here we present our experiences with uniportal VATS lobectomies for NSCLC.

      Methods:
      Between October 2015. and March 2016. twenty-four (24) patients with non-small lung cancer (NSCLC) underwent uniportal VATS lobectomy and mediasitnal lymph node dissection. Surgical access was performed through a 4-5 cm long utilitarian incision at the 5th intercostal space in the anterior axillary line. Anatomical resection of veins, arteries, bronchi and mediastinal lymph nodes followed established oncological principals. Once the operation was completed a single chest tube was inserted in the anterior part of the incision for uniportal VATS.

      Results:
      Fifteen male and nine female patients with an average age of 62.6 years (49-76) were enrolled in the study. Average procedural time was 108 minutes (75min-154min). None of the patients required blood transfusion after the procedure or during the rest of their hospital stay. Average duration of chest drainage was 3.6 days (2-8) and mean hospital stay was 6.3 days (3-10). There were 14 patients with adenocarcinoma and 10 with squamous cell carcinoma. Two patients had prolonged air leak and were treated conservatively. There was no perioperative mortality.

      Conclusion:
      Our initial experiences with Uniportal VATS lobectomy is encouraging as it demonstrated benefits to patients due minimal surgical stress, faster recovery, reduced postoperative pain and shorter hospital stay.The authors strongly believe uniportal VATS surgery should be considered for primary surgical treatment of NSCLC.

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      P1.08-055 - Hand Assisted Thoracoscopic Surgery (HATS) for Metastatic Lung Tumors - Improved Technique for More Safety and Accuracy (ID 5319)

      14:30 - 15:45  |  Author(s): S. Fujino, M. Watanabe, T. Okumura

      • Abstract

      Background:
      Small pulmonary lesions, the localization of which cannot be confirmed by the sight, are often removed surgically with help of several type markers. But they sometimes drop off or dislocate before surgery. It is the most certain to confirm local existence of tumors with help of palpation and remove them surgically. I reported the usefulness of hand assisted thoracoscopic surgery (HATS) for such cases. We removed about 15% more lesions than the number that we expected before surgery using this technique.

      Methods:
      A hand of surgeon was inserted into the bilateral thoracic cavities of patients through a subxiphoid skin incision in supine position in the method of original HATS.

      Results:
      HATS is relative safe and useful technique. But there is only one problem in this technique. Surgeon can palpate whole lungs from the pulmonary apex to a base of lung in right side without circulatory complication. But, in left side, blood pressure sometimes decreases by a surgeon’s arm pressing left ventricle. In such a case, we change patients' position from supine to left side up. Circulatory complications decreases in this improved technique.

      Conclusion:
      HATS in supine position for right side and in left side up position for left side is safer and more accurate method. Improved data got with improved technique will present on the poster of congress.

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      P1.08-056 - Surgical Results of Thoracoscopic Anatomical Sublobar Resections for Early-Stage Lung Cancer (ID 5390)

      14:30 - 15:45  |  Author(s): F. Watanabe, M. Takao, K. Hayashi, I. Yada, H. Shimpo, Y. Suzuki, H. Saiki, T. Sakaguchi, K. Ito, Y. Nishii, O. Hataji

      • Abstract
      • Slides

      Background:
      High-resolution computed tomography (HRCT) has been used to detect ground glass nodules (GGN), and sublobar resections might be currently accepted for patients with early stage malignant GGN. Aim of this study was to evaluate the surgical results of thoracoscopic sublobar resections for early-stage lung cancer.

      Methods:
      Twenty patients (6 males and 14 females, a mean age of 72.5 years) performed surgical treatment for thoracoscopic anatomical sublobar resections from April 2012 to May 2016. Anatomic sublobar resections were selected with the following criteria; stage IA disease with no regional lymph node metastasis; tumor up to 2 cm in diameter; a low tumor standardized uptake value (SUV) evaluated in (18)F fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET) ; predominantly ground-glass appearance on CT imaging. The high resolution CT scanner, Philips Brilliance iCT (Medical Imaging Resources, An Arbor, MI) with both 128 and 256 slice configurations was used. CT data were transferred to an imaging analysis system (Zio station ver.2, Tokyo, Japan) for image reconstruction and we performed preoperative CT-guided marking in surface of near the tumor.

      Results:
      In all 20 cases, the reconstruction of the pulmonary artery and vein could image branches and resected in lung segment. Right side: One case of the upper lobe S1; 5 cases of the lower lobe S6 (3), S8 (1) and S10 (1). Left side: 10 cases of the upper lobe S1+2a, S1+2c, S1+2a+b, S1+2c+S3a, S3b+c, apicoposterior segmentectomy, S3(2) and upper lober trisegmentectomy (2); 4 cases of the lower lobe S6, S8+S9, S10 and basal segmentectomy. All pulmonary nodules were found in the excised target segments with safety margin. According to postoperative pathological examination of the all operative specimens were adenocarcinoma , and the diameters of pulmonary tumors resected were 15.8±3.3 and invasive size were 6.2±3.1 mm. Furthermore, the pathological results were given Atypical adenomatous hyperplasia (2), adenocarcinoma in situ (2), minimally invasive adenocarcinoma (5), Lepidic predominant adenocarcinoma (10) and papillary predominant adenocarcinoma (1).

      Conclusion:
      At the time of writing, local recurrences had not occurred in sublobar resection, so we should be considered for early stage lung cancer in these conditions. Moreover the 3D-CT angiography could be used preoperatively as a tracing method to identify the resected line of lung segment and very useful for anatomic sublobar resections, especially in thoracoscopic surgery.

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      P1.08-057 - Outcomes between Single Port, Two Port and Three Port VATS Pulmonary Resection (ID 6770)

      14:30 - 15:45  |  Author(s): J. Mu, S. Gao, Q. Xue, Y. Mao, D. Wang, J. Zhao, Y. Gao, J. Huang, J. He

      • Abstract
      • Slides

      Background:
      To investigate the difference of outcome between single port , two port and three port VATS pulmonary resection.

      Methods:
      The data of 3217 cases of VATS pulmonary resection from November 2014 to August 2016 in the Department of Thoracic Surgery of National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The following data were compared between two groups: duration of operation, intraoperative blood loss, lymph nodes retrieved, volume of drainage, duration of chest tube, complication rate, postoperative length of stay, hospital cost and surgery cost.

      Results:
      There were 516 patients in single port, 178 patients in two port group and 2523 patients in three port group. Compared with three port group, patients in the single port and two port group had decreased operative time (136.69±55.90 vs 129.09±57.36 vs 122.23±58.38min;P=0.002), decreased intraoperative blood loss(71.06±106.94 vs 57.32±45.21 vs 67.39±93.00ml;P=0.028), decreased chest tube drainage(1037.58±797.56 vs 791.09±535.36 vs 926.21±766.82 mL;P<0.001), reduced duration of chest tube (5.08±2.84 vs 4.53±1.77 vs 4.30±2.29 d;P<0.001), and decreased postoperative length of stay (6.13±3.13 vs 5.73±2.39 vs 5.16±2.42 d,P<0.001). However, the number of lymph nodes retrieved was significantly less in single port and two port compared with that in three port group (13.76±8.96 vs 11.13±9.76 vs 11.78±9.78;P<0.001). There was more patients were diagnosed as benign pulmonary lesions in single port and two port group than in three port group (19.6% vs 19.1% vs 18.6%, P<0.001). There were no significant difference in the complication rate between there three groups(2.7% vs 5.6% vs 3.7%;P=0.789).Figure 1



      Conclusion:
      The outcomes between single port and multiple port VATS lobectomy were comparable. However, compared with three port VATS pulmonary resection, single port and two port VATS pulmonary resection was associated with decreased number of lymph nodes retrieved, which may need further study.

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      P1.08-058 - VATS Lung Resection Analysis from Brazilian Society of Thoracic Surgery Database (ID 6252)

      14:30 - 15:45  |  Author(s): M.T. Ruiz Tsukazan, R.M. Terra, G. Fortunato, S.M. Camargo, H.A. De Oliveira, L.L. Lauricella, D. Pinto

      • Abstract

      Background:
      Lung cancer is the leading cause of cancer related death worldwide when considering both genders. The optimal treatment is complete surgical resection. The objective of this study was to analyze VATS anatomic lung resections in Brazil.

      Methods:
      The Brazilian Society of Thoracic Surgery (BSTS) uses a customized version of the ESTS platform as its national database (BSTS Database). From August to December 2015, 1367 patients were registered. In the current analysis, we included only patients who underwent lung cancer anatomic lung resections by VATS; wedge resections and unspecified cases were excluded.

      Results:
      Out of the 902 anatomical lung resections registered, 516 were lung cancer and VATS performed in 389. Patient’s mean age was 62.5 years, 57.7% were women. PFT were available in 239 with FEV1 81.7% and CFV 88%. ASA score (n=352) was 1 in 19.3%, 2 in 49.7%, 3 in 27.3%, 4 in 3.4% and 5 in 0.3%. The resections performed were lobectomy in 303 cases (77.9%), pneumonectomy in 9 (2.3%), bilobectomy in 5(1.3%) and segmentectomy in 72 (18.5%). Morbidity rate was 21.8% and it varied according to the procedure performed. Overall mortality rate was 1.6% (6). Pathological staging was In situ in 1.3%, IA 55.6%, IB 20.1%, IIA 11.7%, IIB 1.7%, IIIA 9.6% and no IV.

      Conclusion:
      Slightly female predominance and majority of early stage IA and IB lung cancer were found. Our BSTS Database has comparable complications and mortality rates to international series.

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      P1.08-059 - Timing of Surgery after Induction Chemoradiation Therapy for Locally Advanced NSCLC (ID 5695)

      14:30 - 15:45  |  Author(s): H. Melek, A. Demir, G. Cetinkaya, B. Ozkan, S. Sarıhan, M.M. Erol, A.S. Bayram, A. Toker, C. Gebitekin

      • Abstract

      Background:
      The timing of surgery after induction chemoradiotherapy (ChRT) for locally Advanced NSCLC is accepted crucial because of technical difficulties, morbidity and related mortality. Although six to eight weeks’ time interval between induction ChRT and surgery is advocated, precise analysis of the optimal waiting time that maximizes oncologic benefits of ChRT has not been established. We aimed to review our results of pulmonary resections performed after induction ChRT and to determine the effects of time interval on postoperative morbidity, mortality and long term survival.

      Methods:
      We retrospectively reviewed our records for patients undergoing induction ChRT between 1996 and 2015. Timing of treatment was defined as the difference between the last date of radiotherapy and the date of lung resection. The dose of radiotherapy varied from 45Gy to 66Gy. The patients were divided into two groups, surgery less than eight weeks (Group 1) and more than eight weeks (Group 2) following induction ChRT. Type of resection, postoperative complications, 90-days mortality and long-term survival were analyzed. The impact of surgical timing on outcomes was studied through univariable and multivariable analyses.

      Results:
      One hundred and forty-two patients were included into study. The mean time interval between ChRT and surgery was 92.3 days (21-900 days). Sixty-five lung resections were performed less than eight and 77 more than eight weeks. Pulmonary resections were classified as pneumonectomy in 20 patients, lobectomy in 122 patients (of whom, 55 underwent extended resections, chest wall, sleeve etc.). Final pathological examination revealed complete response in 43 (30.3%) of the patients. Major morbidity was observed in 42.2% of the patients [43% (28 of 65pts) in group 1 and 41.5% (32 of 77pts) in group 2, p=0.85]. The overall 90-day mortality rate was 6.3% [7.7% in group 1 and 5.2% in group 2, p=0.54]. The mortality rate after pneumonectomy was 5% (1/20) and 6.5% (8/122) after lobectomy. The 5-year survival rate was 61% vs 47% (p = 0.16). Multivariate analysis showed that timing of surgery after ChRT was not significantly associated with an increased morbidity and mortality that was also not effected by the dose of radiotherapy.

      Conclusion:
      These findings indicate that lobectomy or pneumonectomy can be safely performed eight weeks or more after induction ChRT without affecting surgical morbidity and mortality. Pulmonary resection may be performed safely even one year after ChRT.

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      P1.08-060 - Survival of Patients with Unsuspected N2 (Stage IIIA) Non-Small Cell Lung Cancer (ID 5696)

      14:30 - 15:45  |  Author(s): M. Harada, T. Yamamichi, T. Hishima, A. Asakawa, M. Okui, H. Horio

      • Abstract
      • Slides

      Background:
      There are few studies evaluating the N2 pattern and outcomes when a patient with non–small cell lung cancer (NSCLC) unexpectedly is found to have N2 disease at the time of thoracoscopy or thoracotomy. The objective of this study was to determine the survival of patients who have completely resected, nonsmall-cell, stage IIIA, lung cancer from unsuspected (nonimaged) N2 disease.

      Methods:
      A retrospective review of NSCLC patients treated with lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3 cN0-cN1, pN2 disease) at our institution between January 2008 and December 2011 was conducted. All patients underwent computed tomography scan with contrast, R0 resection with complete thoracic lymphadenectomy, and had unsuspected, pathologic N2 NSCLC. Positron emission tomography scan or invasive staging was added in the attending physician’s choice.

      Results:
      Unsuspected pN2 disease was found in 10.9% of patients (31 out of 284) who underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. Of these, cN0pN2 and cN1pN2 were 9.6% (26 out of 270) and 35% (5 out of 14), respectively. Compare to cN0 group, unsuspected pN2 was more frequent in the cN1group (p=.0023). In terms of the pattern of metastasis, multiple and single pN2 was observed similarly in cN0 and cN1 group (p=.9484). The 5-year overall survival of the entire unsuspected pN2 was 68.5%, and cN0pN2 cohort tended to have better prognosis than cN1pN2 cohort (71.1%(cN0pN2) vs. 50.0%(cN1pN2); p=.0898). No significant difference in 5y-OS between unsuspected single and multiple pN2 could be seen; (70.5%(single) vs. 66.7%(multiple); p=.07803).

      Conclusion:
      This analysis suggests that, in the setting of unsuspected pN2 NSCLC, proceeding with anatomic surgery does not appear to compromise outcomes. As unsuspected pN2 disease was more frequent in cN1 cohort and revealed poor prognosis, perioperative invasive mediastinal staging and additional therapy should be considered.

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      P1.08-061 - Clinical Experience of Rib Resection for Lung Cancer with Chest Wall Invasion Using a Pneumatic High Speed Power Drill System (ID 3843)

      14:30 - 15:45  |  Author(s): Y. Ueda, T. Nakagawa, Y. Tomioka, T. Toyazaki, M. Gotoh

      • Abstract
      • Slides

      Background:
      Rib resection is sometimes required for chest wall tumors or lung cancer with localized chest wall invasion.There are some reports on thoracoscopic rib resection, which may be much less invasive and provide an excellent surgical view of the target. We have used a pneumatic high speed power drill system, commonly used as a dentist’s drill, in order to be accomplished less invasive thoracoscopic rib resection.

      Methods:
      A pneumatic high speed power drill (HiLAN® GA520R B Braun Aesculap, Tokyo, Japan) was inserted in the thoracic cavity and the head of the drill, which has a diamond burr, adequately attached to the rib surface. The rib was then sheared by whittling until dislocated. Cut pieces of bone tissue were removed by suction with saline dropping on the head of the drill. Soft tissue including the parietal pleura, intercostal muscle and vessels were dissected using power devices or an electrical scalpel after cutting the ribs.Figure 1



      Results:
      From February 2014 to date, we have experienced seven patients with chest wall resection using a drill. Hybrid-VATS was performed for four of the patients, while complete-VATS was performed for the remaining three patients.There were no intraoperative issues and the postoperative courses were all eventless. The mean follow-up period is about 13 months. Two of the 7 patients had recurrence of the disease with distant metastasis. However, there is no local recurrence.

      Conclusion:
      A pneumatic high speed power drill is easy to handle and useful for rib resection in lung cancer surgery and possibly better suited even when compared to the Gigli saw or endoscopic rib cutter for selective patients undergoing thoracoscopic surgery. Rib resection using a drill might be less invasive procedure.

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      P1.08-062 - The Short and Long-Term Outcomes of Completion Pneumonectomy Compared with Primary Pneumonectomy (ID 5828)

      14:30 - 15:45  |  Author(s): T. Ueda, K. Sekihara, T. Miyoshi, K. Aokage, T. Hishida, J. Yoshida, M. Tsuboi

      • Abstract

      Background:
      Completion pneumonectomy has been reported to be high morbidity and mortality procedure in lung cancer patients. However, we sometimes have no choice but to apply this procedure for the patients who developed secondary lung cancer in the remaining lung after lung resection, local recurrence, or postoperative complication. In this study, we investigated the short and long-term outcomes of completion pneumonectomy compared with primary pneumonectomy in our single institution.

      Methods:
      Between January 1997 and December 2014, 243 patients who underwent pneumonectomy in our institution were enrolled in this study. Retrospectively, we investigated the postoperative complication, short and long-term outcomes of the patients who underwent completion pneumonectomy (CP) and primary pneumonectomy (PP). CP was defined as pneumonectomy in patients with previous lung resection conducting a hilar manipulation.

      Results:
      Thirty-three patients (14%) of 243 patients underwent CP. CP was performed for 28 malignant tumors and 5 benign diseases. Postoperative severe complication (CTCAE Grade3 or more) occurred in 36% of CP group and 12% of PP group (p<0.01).Especially, bronchopleural fistula (BPF) was more likely to occur in patients undergoing CP (PP 5% vs CP 15%, p=0.03). The incidence of BPF in PP group was related to the side of procedure (right 70% versus left 30%, p=0.01), but those in CP group was not related (right 60% versus left 40%, p=0.57). In the patient with BPF after CP, Bronchial stump coverage was performed in 2 of 5 patients undergoing the right-side procedure, not performed in other 3 of 5 patients (2 left-side and 1 right-side). The 30-day mortality for CP group (9%) was a significantly higher compared with PP group (2%, p=0.04). However, the 90-day mortality (PP 5% vs CP 12%, p=0.14) and the overall survival (PP 47% vs CP 52%, p=0.44 ) were not significant difference between the two groups.

      Conclusion:
      Postoperative morbidity and 30-days mortality rates in CP were higher than those in PP group, but the long-term survival of CP is acceptable compared with PP group. The incidence of left-side BPF is similar to right-side in CP group in this study. It will be also necessary to take preventive procedure against BPF (bronchial stump coverage) in left-side CP.

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      P1.08-063 - Double Primary Malignancies Involving Lung Cancer and Hepatocellular Carcinoma (ID 6361)

      14:30 - 15:45  |  Author(s): H.P. Lee, S.H. Choi, Y. Kim, D.K. Kim, S. Park, H.R. Kim

      • Abstract
      • Slides

      Background:
      The incidence of double primary malignancies (DPM) with lung cancer and hepatocellular carcinoma (HCC) has increased in gradually. However there was a lack of data about the clinical outcomes and factors. We performed a retrospective study to investigate overall survival and characteristics in that patients.

      Methods:
      Between January, 2002 and December, 2013, total 52 patients had DPM. 7 patients were excluded because there was lack of medical record. 3 patients with other malignancies were excluded. We divided the patients into 2 groups. 19 patients were synchronous group that interval of diagnosis between 2 malignancies was shorter than 180 days and other 23 patients were metachronous group.

      Results:
      Among 42 patients with DPM, there were no significant differences in basic characteristics. Median overall survival was 118.97 ± 6.39 months. There was no significant difference in overall survival between synchronous group and metachronous group (p = 0.921). Multivariate analysis revealed that higher lung cancer stage, postoperative therapy due to lung cancer, liver cirrhosis, and history of hypertension were independent factors for overall survival. Figure 1 Figure 2





      Conclusion:
      Lung cancer stage and underlying liver cirrhosis were strongly related to overall survival in patients with DPM involving lung cancer and HCC. Absence of hypertension showed better prognosis in those patients.

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      P1.08-064 - Surgery for Malignant Pulmonary Tumor Invading Proximal Left Main Pulmonary Artery (ID 4407)

      14:30 - 15:45  |  Author(s): F. Tanaka, Y. Nabe, A. Taira, T. Kuwata, S. Oka, Y. Chikaishi, A. Hirai, K. Yoneda, Y. Tashima, K. Kuoroda, N. Imanishi

      • Abstract

      Background:
      Surgery for tumor invading proximal left main pulmonary artery (PA) may be technical challenge, and the current study conducted to assess its feasibility.

      Methods:
      Patients who received surgery for malignant pulmonary tumor invading left main PA, PA proximal to the first branch (usually A3), from 2011 through 2015 in our institute were retrospectively reviewed

      Results:
      Among 32 eligible patients (Table 1), 31 (97%) patients received complete resection with pneumonectomy (n=4) or lobectomy with PA-reconstruction (n=27). Pericardiotomy was necessary for proximal control of main PA in 12 patients, and combined bronchial sleeve resection and reconstruction were performed in 11 patients. Postoperative complications occurred in 7 patients, but a > grade 3 complication (ARDS) occurred in only one patient who received pneumonectomy. There was no operative or in-hospital death.

      Characteristics of Patients (n=32)
      No. of Patients %
      Age, median (range) 70 years (47-85)
      Sex, Female / Male 6 / 26 19% / 81%
      Histology
      ・Primary lung cancer 30 94%
      ・Lung metastasis 2 6%
      Mode of lung resection
      ・Upper lobectomy 27 84%
      ・Pneumonectomy 4 13%
      ・Exploratory thoracotomy 1 3%
      Pericardiotomy 12 38%
      PA-resection 31 97%
      ・Circumferential resection 18
      ・Partial resection 13
      PA-reconstruction 27 84%
      ・Direct closure 25
      ・Patch closure (with pericardium) 1
      ・Vascular conduit (pulmonary vein) 1
      Bronchial sleeve resection 11 34%
      Morbidity 7 22%
      ・Arrythmia 5
      ・Prolonged air leak 2
      ・ARDS 1
      Mortality 0 0%


      Conclusion:
      Lobectomy with PA-resection and reconstruction was feasible to avoid pneumonectomy for tumor invading proximal left PA.

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      P1.08-065 - Resection of Isolated Brain Metastasis Improves Outcome of Non Small-Cell Lung Cancer (NSCLC) Patients: A Retrospective Multicenter Study (ID 6132)

      14:30 - 15:45  |  Author(s): J. Fuchs, M. Früh, A. Papachristofilou, L. Bubendorf, C. Schill, L. Jost, A. Zippelius, S.I. Rothschild

      • Abstract
      • Slides

      Background:
      Metastatic non-small cell lung cancer (NSCLC) is an incurable disease. Selected patients with solitary brain metastasis from NSCLC can achieve long-term survival following metastasectomy. We analyzed the outcome of all consecutive and unselected patients undergoing resection of brain metastases in two cancer centers in Switzerland to assess safety and efficacy of brain metastasis resection in NSCLC.

      Methods:
      119 consecutive NSCLC patients undergoing surgical resection of brain metastases from two centers in Switzerland (University Hospital Basel, Cantonal Hospital St. Gallen) between 2000 and 2014 were analyzed. Measured outcomes were extent of resection, resection status, postoperative complications and overall survival (OS). We used the log-rank test to compare unadjusted survival probabilities and multivariable Cox regression to investigate potential prognostic factors with respect to OS.

      Results:
      Median age was 60.5 years, 56% were male, 74% were smokers, 55% had adenocarcinoma. Median OS of the whole cohort was 18.0 months. 1-year survival rate was 63%, 12% of patients were alive after 5 years. In total, 146 brain metastases were resected; the maximum number of resected metastases was 4 (median: 1). Median diameter of resected metastases was 25 millimeters (range, 6-70 mm). About half of metastases were localized in the frontal cortex or the cerebellum. 86% of patients received postoperative radiotherapy. 63% of patients were treated with whole brain radiation, 12.6% received stereotactic radiotherapy. Median dose of postoperative radiotherapy was 30 Gy. Patients not receiving adjuvant radiotherapy (n=11) had a significantly worse outcome (median OS 9.0 vs. 20.2 months, p=0.002). Patients with more than one brain metastasis (n=21) had a significantly worse outcome compared to those with a solitary metastasis (median OS 13.5 vs. 19.5 months, p=0.006). Also patients with extracerebral metastases (n=33) had a significantly poorer outcome (median OS 14.0 vs. 23.1 months, p=0.005). Patients with non-squamous histology (n=98) had a better outcome than patients with squamous cell carcinoma (median OS 22.6 vs. 12.0 months, p=0.019). 21% of patients experienced postoperative complications, including need for surgical reintervention (5.8%), neurological deficits (4.2%), infection (4.2%), stroke (3.4%) and others (11.8%). The occurrence of postoperative complications was not associated with outcome. In the multivariate analysis existence of extracerebral metastases and resection of more than one brain metastasis were independent negative prognostic factors.

      Conclusion:
      Patients with isolated brain metastasis from NSCLC in the absence of extracranial metastasis should be evaluated for metastasectomy. Prospective trials are needed to characterize the patient population experiencing the greatest benefit from a surgical procedure.

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      P1.08-066 - Prognostic Factors of Post-Recurrence Survival in Patients with Completely Resected Stage III-N2 Non-Small Cell Lung Cancer (ID 5909)

      14:30 - 15:45  |  Author(s): K.W. Shin, S. Cho, S.W. Yum, H. Jang, K. Kim, S. Jheon

      • Abstract
      • Slides

      Background:
      Post-recurrence survival (PRS) after curative resection has been considered a multifactorial process dependent on clinicopathological, biological, and treatment modality in non-small cell lung cancer (NSCLC). The aim of this study is to investigate the prognostic factors for PRS in patients with completely resected stage III-N2 NSCLC.

      Methods:
      Two hundred forty-five patients who had complete resection for pathologic stage III-N2 NSCLC between 2003 and 2014 were enrolled. First, a number of clinicopathological factors were evaluated to find prognostic factors for recurrence by Cox proportional hazards models. Second, the following additional data were evaluated: presence of recurrent symptom, recurrence patterns, treatment modality, use of targeted agents, and recurrence-free interval. The prognostic effects of these factors were analyzed for PRS.

      Results:
      One hundred twenty-four patients experienced recurrence during a median follow-up period of 36.3 months. Univariate analysis showed that vascular invasion, lymphatic invasion, tumor size, number of positive lymph nodes (LNs), and multistation N2 were poor prognostic factors for recurrence. Lymphatic invasion, tumor size, and number of positive LNs were even worse independent prognostic factors for recurrence by multivariate analysis. Of 124 recurred patients, 21 patients (17%) were symptomatic at the time of initial recurrence, and the remaining 103 patients (83%) were asymptomatic. In these asymptomatic patients, recurrence was detected by tumor markers in 3, computed tomography (CT) in 80, or positron emission tomography-CT (PET/CT) in 20 patients. The mean recurrence-free interval was 14.0 months (≤ 12 months in 72, > 12 months in 52 patients). The patterns of recurrence were presented as loco-regional recurrence in 37 (30%), distant metastasis in 33 patients (27%), and both in 54 patients (43%). The types of initial treatment included surgery in 15 (12%), chemotherapy in 68 (55%), radiotherapy in 19 (15%), and chemo-radiation in 16 patients (13%). The median duration of PRS was 30.5 (1-109) months and the 2-year and 5-year of PRS were 54% and 23%, respectively. Univariate analysis identified no symptom of recurrence, only LN metastasis without distant organ metastasis, treatment modality, and a longer recurrence-free interval as good prognostic factors, while no symptom and a longer recurrence-free interval were independent prognostic factors for PRS in a multivariate analysis.

      Conclusion:
      No symptom at the time of recurrence and a longer recurrence-free interval were significant predictors of better PRS in patients that have underwent complete resection of stage III-N2 NSCLC.

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      P1.08-067 - The Feasibility of Lung Second Surgery for 2nd Primary Lung Cancer (ID 4113)

      14:30 - 15:45  |  Author(s): K. Hata, K. Suzuki, T. Matsunaga, K. Takamochi, S. Oh

      • Abstract

      Background:
      2[nd] primary lung cancer often has been encountered because of improvement of treatment outcome for lung cancer. If close follow up was performed after first surgery, 2[nd] primary lung cancer often was detected in early stage. And local therapy was indicated for this 2[nd] primary lung cancer. However, there is no rule whether stereotactic radiation therapy or surgery should be chosen. The aim of this study was to evaluate the feasibility of second surgery.

      Methods:
      We reviewed retrospectively 123 consecutive patients with past history of lung resection who underwent second surgery for 2[nd] primary lung cancer between 2008 and 2015 at our institution. i) These 123 cases were divided into 2 groups, contralateral and ipsilateral surgery groups. The difference between two groups of surgical difficulties (operation time and blood loss) and feasibility (post-operative complication and length of hospital stay) were evaluated by using Mann-Whitney U-test and Fisher’s exact test. ii) 82 cases who underwent contralateral surgery was picked up and divided into 3 groups, both lobectomy, lobectomy and limited surgery and both limited surgery. The difference between 3 groups of surgical difficulties and feasibility were evaluated by using same methods. iii) Furthermore, 41 cases who underwent ipsilateral surgery divided into 4 groups by procedure: completion pneumonectomy, lobectomy, segmentectomy and wedge resection. The difference between 4 groups of surgical difficulties and feasibility were evaluated by using same methods.

      Results:
      i) Not only operation time (161min vs 123min, p<0.001) but blood loss (30g vs 15g, p=0.002) were more in ipsilateral cases than in contralateral cases significantly. However, there was no significant difference in feasibility. ii) In contralateral cases, there were no significant difference between 3 groups in surgical difficulties and feasibility. iii) In ipsilateral cases, completion pneumonectomy had more operation time and blood loss than other procedures significantly (p=0.005, p=0.002, respectively) However, there was no significant difference in occurrence of post-operative complication.

      Conclusion:
      Ipsilateral surgery, especially completion pneumonectomy for 2[nd] primary lung cancer was more difficult procedure. However, ipsilateral and contralateral surgery was equivalent feasibility. Contralateral 2[nd] primary lung cancer is indication for surgery. However, second surgery for ipsilateral 2[nd] primary lung cancer requires careful consideration.

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      P1.08-068 - Salvage Surgical Resection after Curative-Intent Concurrent Chemoradiothrapy for N2-Stage III Lung Cancer (ID 6035)

      14:30 - 15:45  |  Author(s): M. Yamashita, T. Ueno, Y. Maki, R. Sugimoto

      • Abstract

      Background:
      Background A concurrent chemoradiotherapy (CRT) is thought to be the curative treatment for N2 Stage IIIA locally advanced lung cancer (LALC). However, after the CRT the cancer sometimes remained the treatment field. The radical pulmonary resection of residual cancer after CRT is one of the option for the treatment.

      Methods:
      Methods: We retrospectively evaluated 20 patients who received curative-intent CRT and radical surgical resection for LALC from January 2003 to April 2016. The initial treatment for LALC consisted of platinum based 2-drugs with concurrent curative thoracic radiotherapy (60Gy.).

      Results:
      Results: The mean age at the surgery was 62.8 years (range 46~ 80 years), two women and 18 men. The mean interval from CRT to the surgery was 25 months (range 3-96 months). All patients except two cases underwent complete surgical resection with mediastinal nodal dissection including lobectomy in 15 cases, lobectomy with bronchoplasty in 2 cases, pneumonectomy in 2 cases and 1 wedge resection. The bronchial stump was covered with pericardial fat tissue or intercostal muscle. Histological type was adenocarcinoma in 11 cases, squamous carcinoma in 6 cases, large-cell-carcinoma in 2 cases, and combined cell type small-cell carcinoma in one case. The mean operation time was 320 minutes (range 163-649 minutes), and mean blood loss was 868g (range 90-6000g). There was no operative mortality and 8 cases post-operative morbidity such as arrhythmia in 4 cases, atelectasis in 2 cases, pneumonia, ileus and heart failure in each. There was no broncho-pleural fistula or bronchial dehiscence. The 3 and 5 years survival after surgical resection was 70% and 60 % with 43 months median follow-up period.

      Conclusion:
      Conclusion; The radical pulmonary resection after curative-intent concurrent chemoradiotherapy is feasible with careful patient selection, operative procedure and meticulous perioperative care.

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      P1.08-069 - One Surgeon's 30-Year Experience of Surgical Treatment for Pancoast Tumor (ID 5406)

      14:30 - 15:45  |  Author(s): H. Niwa, M. Tanahashi, H. Yukiue, E. Suzuki, N. Yoshii, M. Shitara, T. Fujino, Y. Kaminuma

      • Abstract

      Background:
      Surgical treatment for Pancoast tumor has made marked progress, and the patient outcome has improved significantly over the last three decades. Developments of some new surgical approaches and the application of preoperative chemo-radiotherapy markedly contributed.

      Methods:
      We retrospectively analyzed the patients who received surgical treatment in two institutes between 1984 and 2013. One surgeon planned the surgical treatment and performed the operation in all patients.

      Results:
      Seventy-two patients received surgical treatment. There were 61 males and 11 females, with median age of 61 years old (33-83 years). There were 26 adenocarcinomas, 26 squamous cell carcinomas, 10 large cell carcinomas, and 10 other pathologies. Forty patients received preoperative induction therapy. Twenty-five patients were treated by induction chemo-radiotherapy with a platinum doublet and 40-50 Gy of concurrent radiotherapy. Fourteen patients received radiotherapy alone, and another one patient received chemotherapy alone. The surgical approach was selected based on the tumor location. An anterior approach including Masaoka’s approach, Dartevele’s approach, and Grunennwald’s approach were adopted for 19 patients. Posterior approach, all involving a hook approach was employed in 52 patients. One patient was operated on using both anterior and posterior approaches. Combined resection excluding the chest wall was performed in 59 patients. The brachial plexus (Th1) in 48 patients, thoracic vertebrae in 17, subclavian artery in eleven, and subclavian vein in 5 were removed with the tumor. In 52 patients (72.2%), the tumors were completely removed. The morbidity rate was 37.5% and mortality rate was 2.8%. One patient died of bleeding from rapture of an aortic anastomosis, and another patient died of esophago-pleural fistula. The 5-year survival rate for all patients was 44%, with a median survival time of 19.5 months. The 5-year survival rate based on the operation date was 31.7% for the first half (1984-1999) and 59.1% for the second half (2000-2013) (p=0.035). The 5-year survival rates of patients who received and did not receive induction chemo-radiotherapy were 63.0 and 34.8%, respectively.

      Conclusion:
      The survival rate after surgical therapy for Pancoast tumor significantly improved over the three decades. Preoperative chemo-radiotherapy and the selection of an approach based on the tumor location contributed to the improvement.

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      P1.08-070 - Salvage Lung Surgery: Difficulties and Results (ID 5447)

      14:30 - 15:45  |  Author(s): B. Yoldas, S. Gursoy, A. Ucvet, B.E. Komurcuoglu, E.K. Kirakli

      • Abstract
      • Slides

      Background:
      Thoracic surgeons often encounter lung resections following neoadjuvan treatments. Despite that, sometimes patients have curative chemo or/and radiotherapy treatments according to being inoperable for different reasons at the time of diagnosis. After these treatments due to residual tumour or relapses, surgery might be performed and this kind of surgery is called “salvage surgery”. This surgery has more difficulties and complications because of the adverse effects of definitive therapies. In this study we retrospectively analysed such patients undergone salvage surgery, and looked for an answer if we have to avoid or not?

      Methods:
      Patients operated after curative chemo or/and radiotherapy (4 cycles and more chemotherapy and 66 Gy radiotherapy is accepted as curative radiotherapy) between January 2010 and December 2014 were included in this study and analysed retrospectively. Demographic data, surgical management, morbidity, mortality and survival results were collected.

      Results:
      Having the described criteria 69 cases (62 male, 7 female) were included in the study. Six of the cases had chemotherapy, 8 radiotherapy only and remaining 55 had only chemotherapy (4-12 cycles). At the postoperative period, 5 cases were undergone rethoracotomy, 10 had prelonged air leakage and were externed with “Heimlich Valve” system, 5 had intraoperative vascular injury; 1 chylothorax, 4 secretion retantion requiring bronchoscopy, and 2 (2.3%) mortality occured. The mean follow up time was 27.6±20.5, ranging with 0.1-69.7 months. Five year survival was calculated as 51.9%.

      Conclusion:
      Complications after resective surgery following curative treatments are at acceptable rates. Besides this, the 51.9% five year survival rate seems like a last chance for such patients who have had their definitive treatment.

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      P1.08-071 - Surgery for Lung Cancer with Mediastinal Lymph Node Metastasis - Effectiveness of Extended Bilateral Mediastinal Lymphadenectomy (ID 6359)

      14:30 - 15:45  |  Author(s): T. Yokota, S. Ikeda

      • Abstract
      • Slides

      Background:
      The role of surgery in the treatment of non-small-cell lung cancer (NSCLC) with clinically manifested mediastinal node metastasis is controversial even in resectable cases. Hata et al. used scintigraphy in healthy volunteers to show that main lymphatic route from any pulmonary lobe was connected with both sides of supraclavicular lymph nodes through the superior madiastinal nodes. They considered bilateral mediastinal lymphadenectomy contributes the survival of the patient with NSCLC. Due to anatomical limitation, it is difficult to perform complete dissection of superior mediastinal lymph nodes through the left thoracotomy. We had devised extended bilateral mediastinal lymphadenectomy and lung resection through a median sternotomy (ND3 operation) for Left NSCLC, and reported that it can allow for complete dissection of all stations of mediastinal lymph nodes. The aim of this study is to add knowledge on mediastinal lymphadenectomy by evaluating the feasibility and efficiency of our ND3 operation.

      Methods:
      We retrospectively studied 283 patients who underwent ND3 operation due to Left NSCLC, from January 1988 till December 2015. All operations were performed through the median sternotomy. The lymph nodes around the right and left recurrent laryngeal nerves directly under the thyroid gland,, and then a series of lymph nodes on the bilateral sides along the trachea were dissected. Lymph node station #2R, #4R, #2L, #4L, #3a, #5, #6, #7, ( #8, #9:Left lower NSCLC) and part of #1R, #1L were removed.

      Results:
      Overall 5-year survival rate in the 283 patients was 61.7%. Operative mortality was 3.1%,(1.1% after 2006) Lymph node metastasis to the mediastinum was confirmed in 91 (32.1%) patients (pN2 was 50,pN3α was 23, pN3β was 2, pN3γ was 16).According to pathological stages, five-year survival rate was 88.4% in stage IA, 74.5% in stage IB, 61.3% in stage IIA, 68.4% in stage IIB, 46.8% in stage IIIA, 40.8% in stage IIB. Five-year survival rate were 47.9% in cN2(n=45), 46.7% in cN3α(n=19),47% in pN2(n=50), and 47.5% in pN3α(n=23).

      Conclusion:
      Surgery for Stage III-N2,N3 Lt. NSCLC achieved good long-term survival . Our result suggest that ND3 operation would provide better prognosis in the patients with mediastinal lymph node metastasis, and it does not increase mortality. We can assume that our ND3 operation in Lt. NSCLC with mediastinal lymph node involvement represent feasible, safe, and effective option. It is important to perform curative operation with complete dissection of all station of mediastinal lymph nodes. Surgery should be considered as a first treatment for patients with stage III-N2,N3 Lt.NSCLC.

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      P1.08-072 - The Result of Completion Pneumonectomy for the Local Recurrent Lung Cancer after Radical Lobectomy (ID 4522)

      14:30 - 15:45  |  Author(s): T. Shiraishi, S. Yamashita, A. Iwasaki

      • Abstract
      • Slides

      Background:
      Retrospective review on the result of completion pneumonectomy (CP) for the local recurrent non-small cell lung cancer (NSCLC) following the radical lobectomy, performed by a single institution.

      Methods:
      From 1995 to 2015, 12 consecutive patients underwent CP for cure of loco-regional recurrent NSCLC. Eleven out of these were the cases with recurrent tumor at resection margin of previous surgery and the rest was the case with multiple metastatic tumors within the ipsilateral remaining lung lobe. The right CP was performed for 5 patients (41.6%) and the left for 7 (58.3%).

      Results:
      Operative mortality was 0% and major complications occurred to 3 patients (25%). The operations were performed by the posterolateral thoracotomy for 7 patients, and 5 by the anterior approaches (median sternotomy or hemi-clamshell thoracotomy). The control of hilar components was achieved through an intra-pericardial route in all cases. In two cases, the infiltration of the recurrent tumors were confirmed in the carinal bifurcation. Thus, the completion “sleeve” pneumonectomy was performed. The complete resections were achieved in all patients. Mean observation period was 1313 days after CP at the time of this investigation. Four patients deceased including 2 cancer re-relapse death and 2 cancer unrelated death. There are 8 survivors for more than one year after CP including 4 patients surviving without cancer relapse (mean survival time [MST] of 1214 days) and 4 surviving with either local or distant cancer relapse (MST = 1354 days). Among those 4 survivors with cancer relapse, 3 patients were treated with molecular targeted drugs after gene-mutation survey for susceptibility of specific molecular targeted drugs using tumor specimen harvested from CP surgery. Another patient with cancer relapse was found to be unsuitable for any type of molecular targeted drugs, thus treated with cisplatin based conventional anti-cancer protocol. Five year survival rate for the entire series was 66.7%.

      Conclusion:
      Completion pneumonectomy has been considered as a complex and high risk surgical procedure, however, due to the recent progresses made in the surgical techniques and post-operative management, the CP in the setting of locally recurrent NSCLC became safe and favorable treatment option. More importantly, tumor specimen obtained by the CP can be used for selecting the updated molecular target drugs which might be helpful for patient’s long term survival.

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      P1.08-073 - Experience of Third Primary Lung Tumors after Treatment of First and Second Primary Lung Cancer (ID 3680)

      14:30 - 15:45  |  Author(s): T. Watanabe, T. Koizumi, T. Hirono

      • Abstract

      Background:
      Widespread adoption of lung cancer screening and development of high-resolution computed tomography (HRCT) have led to a marked increase in the detection of early lung cancer in Japan. After curative resection for early lung cancer, second primary lung cancers develop in a significant proportion. The majority of these cancers are detected at an early stage because of careful follow-up using HRCT. In our experience, more than 80% of these patients were treated with surgery or radiation therapy, and some of them have acquired with long-term survival. Recently we have experienced with third primary lung tumors in long-term survivors. In this paper, we reviewed the incidence, management, and outcome of third primary lung tumors.

      Methods:
      Between April 1996 and March 2016, 1194 patients underwent complete resection for primary lung cancer in our institution. Of these individuals, patients who developed a third primary lung tumor were selected for this study.

      Results:
      Of 1194 consecutive patient, 105 patients (8.8%) developed second primary lung cancers, and 11 patients (1%) of them developed third primary lung tumors. The patients included 10 men and one woman. The initial resection for primary lung cancer was lobectomy in 9 patients and segmentectomy in 2. Surgical resection for second primary lung cancer was performed in 8 patients, and radiation therapy was performed in 3. Four of the 11 patients underwent resection for third primary lung tumors. One patient had completion pneumonectomy, 1 had segmentectomy, and 2 had wedge resections. Five patients were treated by radiation therapy. The two remaining patients received best supportive care. Survival after resection of first primary lung cancer ranged from 50 months to 185 months, with a median survival of 138 months and an average survival of 137 months. Currently, 4 patients are alive without evidence of recurrence. Among them, three patients were treated by their third pulmonary resection, and one patient was treated by radiation therapy.

      Conclusion:
      During 20 years, third primary lung tumors were diagnosed in only 11 patients (1%). But long-term survivors after resection of lung cancer are increasing. Careful follow-up and early detection of second primary lung cancers using HRCT will induce the increase of experience for treatment of third primary lung tumors. In our little experience, aggressive surgery for third primary lung tumors may improve survival.

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      P1.08-074 - Effect of Intrapleural Perfusion Hyperthermic Chemotherapy in Non-Small Cell Lung Cancer with Pleural Seeding (ID 5937)

      14:30 - 15:45  |  Author(s): H. Jang, K.W. Shin, S. Cho, S.W. Sung, K. Kim, S. Jheon

      • Abstract

      Background:
      Pleural seeding is generally associated with poor prognosis in advanced non-small cell lung cancer (NSCLC). Although palliative chemotherapy is the mainstay modality for these patients, intrapleural perfusion hyperthermic chemotherapy (IPHC) may be a good alternative. The aim of this study was to evaluate the efficacy of IPHC and predictive factors for longer survival in NSCLC with pleural seeding.

      Methods:
      From 2003 to 2014, 51 patients who underwent IPHC for NSCLC with pleural seeding at the first operation in 36 or after postoperative recurrence in 16 patients were enrolled. IPHC was performed with cisplatin (dose:150mg/m[2]) for 90 minutes. For patients with pleural seeding at first operation, parenchymal resection was performed and mediastinal LN was evaluated. We included some procedures other than pre-IPHC pleural biopsy, pre-IPHC lavage cytology, post-IPHC lavage cytology, and post-IPHC pleural biopsy. Subjects were divided into two groups: group I is shorter survivor of less than 36 months and group II is longer survivor of more than 36 months of overall survival duration.

      Results:
      There were 22 male patients and the mean age was 59.6 years. There were 7 patients in pathologic stage T1, 28 in T2, 13 in T3, and 3 in T4. With respect to N stage, 18 patients in N0, 9 in N1, 17 in N2, and 8 in Nx. Major post-IPHC complication was acute renal insufficiency (n=4). All patients, except 3, received systemic chemotherapy after IPHC. Pleural seeding aggravation was seen in 28 patients, and the development of pleural effusion was observed in 5 patients after IPHC. EGFR mutation was examined in 38 patients after 2007; of which, 20 patients showed to have EGFR mutation. Targeted agents were used in 32 out of 51 patients. The mean overall survival was 36.4 months (5.9-98.0); 28 patients died during the follow-up period. The 2-year and 5-year survival rates were 75.7 % and 39.8%, respectively. The prognostic factors for patients with overall survival of more than 36 months, seen in 19 patients, were old age, negative post-IPHC pleural biopsy, and presence of EGFR mutation.

      Conclusion:
      IPHC appears to be a safe procedure for advanced lung cancer patients with pleural seeding, and IPHC may provide better survival to only a highly selective group of patients. Old age, negative post-IPHC pleural biopsy, and presence of EGFR mutation are the predictive factors for longer survivor.

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      P1.08-075 - Salvage Surgery for Stage IV Non-Small Cell Lung Cancer (ID 3816)

      14:30 - 15:45  |  Author(s): H. Kojima, S. Hayashi, K. Mizuno, Y. Yasuura, R. Shimizu, H. Kayata, S. Takahashi, M. Isaka, T. Takahashi, Y. Ohde

      • Abstract
      • Slides

      Background:
      There have been few reports regarding salvage surgery in patients with primary lung cancer, and the efficacy of salvage pulmonary resection for primary lung cancer have not been fully elucidated. Furthermore, salvage surgery for stage IV non-small cell lung cancer have been rarely performed. The purpose of this study is to evaluate the efficacy of salvage surgery for stage IV non-small cell lung cancer.

      Methods:
      We performed a retrospective analysis of 4 patients who underwent salvage pulmonary resection for stage IV non-small cell lung cancer between September, 2002 and September, 2015 at the Shizuoka Cancer Center Hospital.

      Results:
      Of 2606 cases of surgically resected lung cancer in our hospital, 4 cases (0.15%) of salvage surgery for stage IV non-small cell lung cancer patients were performed. There were 2 men and 2 women. The range of age was 38-63 years old (median 57 years old). The histological type was 3 adenocarcinomas and one large cell carcinoma. The reasons diagnosed stage IV non-small cell lung carcinoma were 2 liver metastasis, 1 brain metastasis, and 1 abdominal lymph node metastasis. All cases have administered chemotherapy, and salvage pulmonary resection was performed for persistent or recurrent primary lung tumors. The median period for surgery from chemotherapy was 17.5 months (range 13-55 months). The lobectomy was performed in all cases. There were no complications after surgery and the mean length of hospital stay was 9 days. Postoperative disease free survival of all patients was 2, 2, 5, 52 months (median 3.5 months), respectively. 3 cases had recurred after surgery and all of them were distant recurrence. 2 cases were died of disease (survival time 15, 42 months, respectively), 1 case was alive with recurrent disease, and 1 case was alive with no recurrent disease (survival time 52 months).

      Conclusion:
      Although almost all cases had developed distant recurrence after surgery early, one case was long-term survival. Salvage surgery might have been effective for highly selected stage IV non-small cell lung cancer patients.

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      P1.08-076 - Recurrence Patterns in Lung Cancer Patients Treated with Protocol Based Multimodality Treatment at a Tertiary Care Cancer Center in India (ID 4940)

      14:30 - 15:45  |  Author(s): A. Jakhetiya, V. Kumar, S.S. Deo, N.K. Shukla, D. Pandey, P. Malik, D. Jain, S. Kumar

      • Abstract
      • Slides

      Background:
      Wide disparity has been reported in lung cancer survival between high income countries (HIC) and low-middle income countries (LMIC). The aim of present study is to analyze treatment outcomes and relapse patterns following protocol based multimodality management including quality control surgery in lung cancer patients from a tertiary care cancer center in India (LMIC).

      Methods:
      A retrospective analysis of computerized prospective clinical database of lung cancer patients treated consecutively during January 2006 to June 2015, in the department of Surgical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India was performed. The AJCC/ TNM (2010) staging system was referred for staging purpose. All patients were offered protocol based trimodality therapy (Surgery + Systemic therapy + Radiotherapy). Clinical spectrums, Follow up patterns, compliance to treatment and relapse patterns were analyzed.

      Results:
      A total of 136 patients underwent surgery during this period. Mean age at presentation was 53.16 years (SD 13.56) with male predominance (78%). Cough (58%) and Hemoptysis (42%) were most common presenting symptoms. Majority operated upfront (70%) and 126 (92.6%) underwent curative resection. Most common procedure was lobectomy (52%) however 42 patients (30%) underwent pneumonectomy due to advanced stage. Most common histology was squamous cell carcinoma (45%) followed by adenocarcinoma (36%). Most common stage was IIIA (30%) followed by IIB (27%). Median duration of surgery and hospital stay was 180 minutes and 7 days respectively. One patient developed post operative pneumonia and succumbed to it while 15 others developed major postoperative morbidity which was managed conservatively. Total of 30% received adjuvant chemotherapy and 11% received adjuvant radiotherapy. After median follow up of 7.26 months 16 (11.75%) patients had documented recurrences. Out of 16 patients 3 had isolated loco-regional, 4 had loco-regional with systemic and 9 had systemic recurrence. Among systemic recurrences five had multiple visceral, bone and brain in three each followed by contralateral lung in two patients.

      Conclusion:
      Majority of lung cancer patients presents in advanced stage. With good protocol based approach including quality-controlled surgery excellent outcomes can be achieved which are comparable to western world even in resource constrained low middle income countries like India.

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      P1.08-077 - Comparison of Pulmonary Resection for Lung Cancer after Radical Chemoradiation with That after Induction Chemoradiation (ID 6309)

      14:30 - 15:45  |  Author(s): Y. Hida, K. Kaga, M. Aragaki, R. Nakada-Kubota, H. Shiiya, H. Usui, Y. Matsui

      • Abstract

      Background:
      Induction chemoradiation (ICR) for advanced non-small cell lung caner is often limited to 45Gy or less to avoid increase of perioperative complications. On the other hand, pulmonary resection after definitive chemoradiotherapy (DCR) is increasing. In this study, we compared three groups, pulmonary resection following low dose ICR (LCR), that following high dose ICR (HCR) and that after DCR.

      Methods:
      From 1997 to 2015, we had 24 pulmonary resections following CR. Among 13 ICR, 7 were LCR and 6 were HCR. There were 11 DCR. Intercostal muscle flaps were used in 1 LCR, 6 HCR and 1 DCR. Omental flaps were used in 8 DCR.

      Results:
      There was no mortality in any groups. In comparison with LCR and HCR, operation time (min) were 352 and 344, estimated blood loss (ml) were 440 and 280, morbidity (%), 86 and 50. Although operation time was longer (470 min) and there were more blood loss (820 ml) in DCR, there was no significant increase of peri- and post-operative complications. 2-year recurrence free survival and 5-year over all survival rates (%) were 43 and 29 in LCR, 40 and 60 in HCR, and 58 and 52 in DCR.

      Conclusion:
      High dose ICR may contribute to better local control and longer survival. Pulmonary resection after DCR is as safe as that following ICR.

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      P1.08-078 - Does Surgery Have Real Benefit in Resectable Oligometastatic NSCLC? (ID 4106)

      14:30 - 15:45  |  Author(s): O. Pikin, A. Ryabov, V. Glushko, K. Kolbanov, A. Amiraliev, D. Vursol, V. Bagrov, V. Barmin

      • Abstract
      • Slides

      Background:
      The prognosis in patients with distant metastases of NSCLC is generally poor. Surgical resection of isolated distant metastases in NSCLC patients is not widely accepted and chemotherapy is usually administered. The study was aimed to evaluate the long-term results and prognosis after surgical resection of oligometastases in NSCLC patients.

      Methods:
      139 patients with isolated distant metastases of NSCLC (M1a – 38, M1b – 101) operated on in our clinic from 1998 to 2011 were included in the retrospective trial from the prospective database. Solitary brain metastasis was diagnosed in 82, pleural metastases – in 21, contralateral lung – in 17, adrenal metastases – in 11, others – in 8 patients. Synchronous metastases were detected in 61 (43,9%), metachronous – in 78 (56,1%) patients. In patients with pleural dissemination lung resection with pleurectomy followed by PDT was carried out. The primary lung cancer was completely resected in all cases. Surgery included pneumonectomy – in 17, lobectomy/bilobectomy – in 112 and sublobar resection – in 10 patients. Median follow up is 52 month.

      Results:
      Postoperative complications were registered in 10 (7,2%) patients, mortality – 2,2%. Median survival after pulmonary resection and removal of brain metastasis was 23,0 months, contralateral lung resection – 12,0, after lung resection with pleurectomy – 11,0 and adrenalectomy – 9,0 months. 5-year survival after lung resection and brain metastasectomy was 20,6%, contralateral lung resection – 12,0%, lung resection and pleurectomy (limited pleural spread) – 10,7%. No one survived more than 2 years after adrenalectomy. Survival of patients in N0-1 cases was significantly better in all groups: after brain metastasectomy - 34,5% vs 0%, contralateral lung resection – 28,0% vs 0%, pleural dissemination – 4,7% vs 0% in N2 positive patients with median survival 19,0 and 8,0; 15,0 and 8,0; 23,0 and 10,0 months respectively. Overall survival was worse in synchronous group if compare with metachronous detection: after brain metastasectomy 10,0% and 19,8%; contralateral lung resection 0% and 32,0% with median survival 18,0 and 25,0; 11,0 and 21,0 months respectively. Multivariate analysis confirmed that positive N2 status (p<0.001) and synchronous detection of oligometastatic disease (p=0.002) were independent unfavorable prognostic factors.

      Conclusion:
      Aggressive surgery in patients with oligometastatic NSCLC is justified in selected patients with solitary brain, contralateral lung metastasis and limited pleural dissemination, especially in N0-1cases and metachronous disease. Surgical resection should be whenever avoided in patients with oligometastatic lung cancer and positive N2 status.

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      P1.08-079 - Sulvage Surgery after Definitive Radiotherapy or Chemoradiotherapy for Lung Cancer (ID 4262)

      14:30 - 15:45  |  Author(s): N. Yamasaki, T. Tsuchiya, K. Matsumoto, T. Miyazaki, R. Kamohara, T. Obata, D. Taniguchi, T. Yamasaki, D. Nakamura, K. Tabata, T. Nagayasu

      • Abstract
      • Slides

      Background:
      Reports of salvage surgery especially bronchoplasty after definitive radiation therapy for locally advanced lung cancer are small. In addition, reports of surgery after stereotactic body radiotherapy (SBRT) are also small.

      Methods:
      Between 2011 and 2015, 3 patients who underwent salvage pulmonary resection after definitive radiation therapy (Group A) and 3 patients after SBRT (Group B) were identified.

      Results:
      Group A: One of two patients who underwent boronchoplasty failed in anastomosis failure. A 40-year-old woman underwent right upper sleeve lobectomy after chemo-radiation therapy including bevacizumab for primary lung adenocarcinoma (cT3N2M0 Stage IIIA). Two months after surgery, anastomosis dehiscence occurred. She underwent right completion pneumonectomy after preparing an omental flap. Bronchial stump was closed in overholt method with wrapping of omental flap. After surgery, left kidney and supraclavicular lymph node metastasis were detected, she was administered crizotinib. She is alive at 48 months after surgery. The other two patients are alive without recurrence at 8 and 35 months, respectively. Group B: The dose of radiation was 48Gy (12 Gy x 4 fractions ). Period from SBRT until surgery was 14, 18, 30 months, respectively. One patient underwent SBRT for second lung cancer after left upper lobectomy for first lung cancer. He died of respiratory failure on 103 days after surgery. The clinical courses of other two patients were uneventful. One patient died of distant metastasis at 7 months, and other one is alive without recurrence at 8months. There were no severe adhesion on both hilar and chest wall after SBRT.

      Conclusion:
      Caution is needed in the salvage pulmonary resection after chemo-radiation therapy including bevacizumab. On the other hand, there was not strong influence to the bronchial stump after SBRT.

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      P1.08-080 - Bilobectomy for Lung Cancer: Analysis of Indications, Postoperative Results and Long-term Outcomes (ID 6220)

      14:30 - 15:45  |  Author(s): D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari

      • Abstract

      Background:
      Bilobectomy for lung cancer is considered a high risk procedure for the increased postoperative complication rate and the negative impact on survival. We analyzed the safety and the oncologic results of this procedure.

      Methods:
      We retrospectively reviewed patients who underwent bilobectomy for lung cancer between October 1998 and December 2015. Age, gender, bilobectomy type and indication, complications, pathology, stage, and survival were analyzed.

      Results:
      Bilobectomy was performed on 166 patients (122 men; mean age, 62 years. There were 87 upper-middle and 79 middle-lower bilobectomies. Indications were tumor extending across the fissure in 37 (22.3%) patients, endobronchial tumor in 44 (26.5%), extrinsic tumor or nodal invasion of bronchus intermedius in 70 (42.2%), and vascular invasion in 15 (10%). An extended resection was performed in 25 patients (15.1%). Induction therapy was performed in 47 patients (28.3%). Thirty-day mortality was 1.2% (n=2). Overall morbidity was 43.4%. Mean chest tube persistence was 7 days (range, 6-46 days). Overall 5-year survival was 58%. Significance differences in survival were observed among different stages (stage I, 70%; stage II, 55%; stage III, 40%; p=.0003) and the N status (N0, 69%; N1, 56%; N2, 40%; p=.0005). Extended procedure (p=.0003) and superior bilobectomy (p=.0008) adversely influenced survival. Multivariate analysis demonstrated that an extended resection (p=.01), an advanced N disease (p=.02), and an upper-mild lobectomy (p=.02) adversely affected prognosis.

      Conclusion:
      Bilobectomy is associated with a low mortality and an increased morbidity. Survival relates to disease stage and N factor. Optimal prognosis is obtained in patients with lower-middle lobectomy without extension of the resection.

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      P1.08-081 - Resection of T4 Non-Small Cell Lung Cancer Invading the Spine (ID 6229)

      14:30 - 15:45  |  Author(s): D. Galetta, L. Spaggiari

      • Abstract

      Background:
      Surgical treatment of non-small cell lung cancer (NSCLC) invading the spine is controversial. We evaluated surgical results and long-term outcome of patients with T4 NSCLC who underwent vertebral resection (VR) due to the infiltration by lung tumor.

      Methods:
      Retrospective analysis of 16 consecutive patients undergoing VR for NSCLC invading the spine between 1998 and 2015 was performed. Ten patients (62.5%) received induction therapy. Vertebral resection was divided into 5 types; type 1: only transverse process; type 2A: transverse process with a portion of the vertebral body; type 2B: a portion of vertebral body without transverse process; type 3, hemivertebrectomy; type 4: total vertebrectomy.

      Results:
      There were 15 men and one woman with a median age of 62 years (range, 41-80). Ten patients had induction therapy. Vertebral resection included 3 type 1 resection, 6 type 2A, 4 type 2B, 2 type 3, and 1 type 4. Pneumonectomy was performed in 3 patients, lobectomy in 7, segmentectomy in 3 and wedge in 3. Complete resection was achieved in 14 patients (87.5%). Surgical nodal status was N0 in 11 patients, N1 in 2, and N2 in 3, each. There were no postoperative mortality. Morbidity was observed in 7 patients (43.7%), including 1 (6.2%) neurologic complication, 3 (18.7%) ARDS, and 2 (12.5%) cardiac . Seven patients (43.7%) are alive without disease after e mean follow up of 44.4 months. The 1- and 5-year predicted survivals were 79% and 40.4%, respectively. Patients without nodal involvement had the best prognosis (56.3% vs 0%; p=0.0009). Induction therapy did not influence survival.

      Conclusion:
      Resection of NSCLC with vertebrectomy is technically demanding and is associated with acceptable morbidity. However, an encouraging long-term survival observed in this series suggest that resection could be a valid option in selected patients with vertebral invasion by NSCLC.

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      P1.08-082 - Surgical Techniques and Long-Term Results of the Pulmonary Artery Reconstruction in Patients with Lung Cancer (ID 6216)

      14:30 - 15:45  |  Author(s): D. Galetta, A. Borri, R. Gasparri, F. Petrella, L. Spaggiari

      • Abstract

      Background:
      Pulmonary artery (PA) reconstruction for lung cancer is technically feasible with low morbidity and mortality. We assessed our experience with partial or circumferential resection of PA during lung resection.

      Methods:
      Between 1998 and 2015, we performed PA angioplasty in 150 patients with lung cancer. Seventy-five patients received induction chemotherapy (IC). Partial PA resection was performed in 146 cases. PA reconstruction was performed by running suture in 113 and using a pericardial patch in 33. A circumferential PA resection was performed in 4 patients and reconstruction was made in PTFE and by a custom-made bovine pericardial conduit each. Bronchial sleeve resection was associated in 56 cases. Thirty-two patients had stage I disease, 43 stage II, 51 IIIA, and 17 IIIB. Seven patients had a complete response after IC.

      Results:
      Thirty-day mortality was 3.3% (n=5); two of these patients had a massive hemoptysis leading to death; 33 patients had pulmonary complications, 28 cardiac, 17 air leaks. Overall 5- and 10-year survival was 50% and 39%, respectively. Five- and 10-year survival for stages I and II versus stage III was, respectively, 66% versus 32% and 56% versus 20% (p<.0001). Five-year survival was 61% for N0 and N1 nodal involvement versus 28% for N2, respectively; 10-year survival was 45% versus 28% (p=.001). IC did not influence survival. Multivariate analysis yielded advanced stage, N2 status, and squamous cell carcinoma as negative prognostic factors.

      Conclusion:
      PA reconstruction is safe, with excellent long-term survival. Our results support this technique as an effective option to pneumonectomy for patients with lung cancer.

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      P1.08-083 - Hyperthermic Pleural Lavage for Pleural Metastases (ID 5343)

      14:30 - 15:45  |  Author(s): P.L. Thompson, D.L. Miller, J.D. Whetstone, I. Bonta, C. Parks, R. Bechara

      • Abstract

      Background:
      To evaluate the safety and efficacy of hyperthermic pleural lavage (HTPL) with cisplatin in patients who have undergone cytoreductive surgery pleurectomy/decortication (PD) for isolated chemoresistant pleural metastases (PM). This may be an alternative treatment for patients with isolated pleural metastases with controlled primary disease.

      Methods:
      After Health Care System and Cancer Committee approval, 10 patients with unilateral chemo resistant pleural metastasis were registered prospectively. The patients’’ primary sites of malignancy were under control for a median of 40 months (range, 28-76). Patients underwent a unilateral radical P/D and lymph node dissection, 60 minute pleural lavage (1,500 – 1,700 cc/min) with 225 mg/m2 of cisplatin at 42°C. Cisplatin levels were drawn at time zero, 1 hour, 4 hours, and 24 hours after completion of HTPL.

      Results:
      Median age was 53 years (range, 38-64); 7 patients (70%) were women. Primary tumor: breast 5, colon 2, and thymic, renal cell and anal cancer 1 each. Surgical approach was a thoracotomy in 9 patients (90%). Morbidity included atrial fibrillation in 3 (30%), and acute respiratory distress syndrome in 1 (10%). Median hospital stay 7 days (range, 4-14). Serum cisplatin levels peaked at 4 hours after lavage; none to toxic range. Median dose of cisplatin was 386 mg (range, 299-450); no patient developed renal insufficiency. Median follow up was 10 months (range, 1-15). 8 patients had no signs of malignant disease at last follow up; 1 patient (anal cancer – 6 months) developed local recurrence and 1 patient (renal cell cancer – 9 months) developed contralateral pleural disease. All patients experienced improved quality of life, respiratory function, and reduced pleuritic pain.

      Conclusion:
      Surgical cytoreduction of chemoresistant PM followed by HTPL with cisplatin was well tolerated with no cisplatin-related toxicities. Early results are promising. This novel treatment for patients with isolated secondary PM represents the first series reported. Longer follow-up is warranted to determine a survival and quality of life advantage as well as defined inclusion and exclusion criteria.

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      P1.08-084 - Treatment for Elderly Patients with Clinical Stage I Non-Small Cell Lung Cancer; Surgery or Stereotactic Body Radiotherapy? (ID 3906)

      14:30 - 15:45  |  Author(s): T. Miyazaki, T. Yamazaki, D. Nakamura, N. Yamasaki, T. Tsuchiya, K. Matsumoto, R. Kamohara, G. Hatachi, T. Nagayasu

      • Abstract
      • Slides

      Background:
      The number of elderly lung cancer patients requiring surgery has been increasing due to the aging society and less invasive perioperative procedures. Stereotactic body radiotherapy (SBRT) is one of the effective treatments for early stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to compare the outcome of pulmonary resection to SABR for elderly clinical stage I NSCLC in our hospital.

      Methods:
      Over 80-year-old patients with clinical stage I NSCLC between August 2008 and December 2014 were treated either surgery or SBRT at Nagasaki university hospital. Propensity score matching (PSM) was performed to reduce selection bias in various clinicopathological factors including age, gender, tumor size, carcinoembryonic antigen (CEA), Charlson comorbidity index (CCI), Glasgow prognostic scale (GPS) and forced expiratory volume in one second (FEV1.0) were compared between surgery and SBRT.

      Results:
      Pulmonary resection was performed in 57 cases, SABR in 41 cases. In surgery group, operations included 34 lobectomies, 23 limited resection (segmentectomy and wedge resections). Systemic lymph node dissection was 16 and limited dissection was 41 cases. In SABR group, 17 cases (41.5%) were not proven in histology. 27 cases were given 48 Gy by 4 fractions, 14 were 60 Gy by 10 fractions, respectively. No treatment deaths were observed. Before PSM, the 5 year overall survival (OS) in surgery (68.3%) was significantly better than that in SBRT (47.4%, p=0.02). the 5 year disease specific survival (DSS) (94.1%, 78.2%, p=0.17, respectively) was not significant. Similar characteristics were identified in age (82 years), gender, tumor size (2.2 cm), CEA (3.6 ng/ml), CCI (1), GPS (0) and FEV1.0 (1.7 Litter) after PSM. The difference in 5 year OS became insignificant between the matched pairs (57.0%, 49.1%, p=0.56, respectively). 5 year DSS was not significant (87.1%, 70.2%, respectively). Both treatments for elderly clinical stage I NSCLC were acceptable though unknown histology and precise lymph node status still existed as important bias.

      Conclusion:
      Surgery for early stage NSCLC is a safe and feasible treatment. SABR could be effective and a good option for early stage NSCLC.

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    PC01 - Pro Con Session: Invasive Mediastinal Staging for N2 Disease (ID 323)

    • Type: Pro Con
    • Track: Radiology/Staging/Screening
    • Presentations: 4
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      PC01.01 - Introduction & Vote (ID 6872)

      14:30 - 15:45  |  Author(s): H. Prosch

      • Abstract
      • Slides

      Abstract not provided

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.

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      PC01.02 - Invasive Staging and Restaging (ID 6594)

      14:30 - 15:45  |  Author(s): C. Dooms

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The aim of mediastinal staging is to exclude with the highest certainty and the lowest morbidity patients with mediastinal nodal disease. The concepts of decision analysis and Bayes’ theorem form the basis for a mediastinal staging strategy. The goal of the clinical staging strategy is to lower the post-test probability sufficiently so that it falls below a testing threshold, which ascertains the clinician that the result is accurate. The ESTS working group considers a rate of unforeseen mediastinal nodal disease at the time of anatomic resection with lymph node dissection less than 10% as acceptable.[1] Contrast-enhanced multi-detector CT (computed tomography) scanning has an excellent spatial resolution but is an imperfect means of staging the mediastinum. A Cochrane review evaluated integrated positron emission tomography (PET) - CT for assessing mediastinal lymph node involvement in NSCLC.[2] The review showed that the accuracy of PET-CT is insufficient to allow management on PET-CT alone, but PET-CT can be used to guide clinicians in the next step (either a biopsy or direct to surgery). The suboptimal specificity of mediastinal lymph nodes positive on PET-CT requires a tissue confirmation. There are conditions where invasive staging is also mandatory despite a normal mediastinum on PET-CT as the prevalence of N2/N3 disease remains significant. These conditions include a primary tumour >3 cm, any central primary tumour, PET/CT hilar N1 disease, or low FDG uptake in the primary tumour.[1] Cervical Mediastinoscopy. A conventional cervical mediastinoscopy through a pretracheal suprasternal incision was introduced in 1959 and for decades considered the gold standard for invasive mediastinal nodal staging. Recently, a very large (N=721 patients; prevalence of mediastinal nodal disease 47 %) retrospective single center study reported on safety and efficacy of cervical mediastinoscopy performed by general thoracic surgeons.[3] There was no mortality, a low perioperative complication rate at 1.3 %, and an unexpected hospital (re)admission rate of 0.46 %. The sensitivity, negative predictive value and post-test probability were 0.90 (95% CI 0.87-0.92), 0.92 (95% CI 0.90-0.94), and 0.09 (95% CI 0.07-0.11), respectively. It is performed under general anesthesia and allows a full mapping of the ipsilateral and contralateral superior mediastinal lymph nodes. Since 1995, the use of video techniques has been introduced leading to video-assisted mediastinoscopy (VAM) clearly improving visualization and teaching. In addition, VAM allows bimanual dissection with possibilities to perform nodal dissection and removal rather than sampling or biopsy. The ESTS working group recommends performing VAM.[1] Endoscopic ultrasonography (EUS) en endobronchial ultrasonography (EBUS). In the last decade, the predominant role of cervical mediastinoscopy has been challenged by EUS and EBUS using a convex probe. When mediastinal nodal staging is required, systematic nodal sampling seems feasible but some primary choices have to be made. At least mediastinal nodal stations 4R, 4L and 7 should be sought. To avoid contamination, the order of sampling should begin at the level of N3 stations followed by N2 stations before N1. There is no evidence to suggest that sampling of all visible nodes in each nodal station is superior to a systematic nodal sampling of the largest measuring ≥5 mm or PET-positive node in each station. It must be stressed that EBUS cannot access the prevascular nodes (station 3a), the subaortic and para-aortic nodes (stations 5 and 6) as well as the paraesophageal and pulmonary ligament nodes (stations 8 and 9). Some of these nodes (stations 8 and 9) can however be reached from the esophagus. Therefore the use of the EBUS scope is extended to an esophageal exploration with EUS-B sampling of stations 4L, 7, 8 and 9. In terms of safety, EBUS and EUS have a low complication or serious adverse event rate of 1.4 and 0.3%, respectively.[4,5] The two staging strategies, surgical staging alone on the one hand and combined EUS/EBUS followed by surgical staging whenever endosonography was negative on the other hand, were compared in a pivotal randomized controlled trial (RCT).[6] It was concluded that invasive mediastinal nodal staging should start with combined linear endosonography, as the trial showed that a staging strategy starting with combined linear endosonography (EUS+EBUS) detected significantly (P=0.02) more mediastinal nodal N2/N3 disease compared to cervical mediastinoscopy alone, resulting in a significantly higher sensitivity of 0.94 (95%CI 0.85-0.98) compared to 0.79 (95%CI 0.66-0.88), respectively.[6] Another RCT suggested that EBUS-TBNA is the preferred primary procedure in combined linear endosonography for mediastinal nodal staging of resectable stage I-III lung cancer.[7] There is no RCT comparing combined EBUS-EUS(-B) to EBUS-TBNA alone for mediastinal nodal staging, but a recent meta-analysis suggested that the combined EBUS-EUS is more sensitive than EBUS-TBNA alone to detect mediastinal nodal disease.[8] The absolute increase in sensitivity of the combined approach compared to EBUS-TBNA alone depends on the quality of the EBUS-TBNA procedure, but published studies suggest an increase in sensitivity up to 10%. Overall, a confirmatory VAM is still warranted for the individual patient with a negative combined linear endosonography as this further lowers the post-test probability. This has been shown within ASTER for patients with clinical N2/3 disease on PET-CT (prevalence of mediastinal nodal disease 63%), as the post-test probability of a negative linear combined endosonography of 20% could be lowered to 5% by adding a cervical mediastinoscopy.[9] A recent prospective cohort study on clinical stage II lung cancer based on N1 disease on imaging (prevalence of mediastinal nodal disease 24%) showed that the post-test probability of a negative endosonography was 19%, which could be lowered to 9% by adding a cervical mediastinoscopy.[10] In conclusion, combined EBUS-EUS(-B) linear endosonography is the standard for initial baseline mediastinal nodal staging, but a VAM is still recommended after a negative (or incomplete) combined linear endosonography. Mediastinal restaging after induction therapy for locally advanced stage III NSCLC is an important prognostic factor. In the context of a 40-50% prevalence of residual mediastinal disease after induction therapy, a first cervical VAM as a restaging technique seems to be the most accurate method for nodal assessment.[1] Overall, limited literature reported a sensitivity and NPV for linear endosonography that is lower than for a first mediastinoscopy.

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      PC01.03 - No Invasive Staging Nor Restaging (ID 6595)

      14:30 - 15:45  |  Author(s): E. Lim

      • Abstract
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      Abstract not provided

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      PC01.04 - Discussion & Vote (ID 6873)

      14:30 - 15:45  |  Author(s): W. Weder

      • Abstract
      • Presentation

      Abstract not provided

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    SC06 - Novel Therapies in Malignant Pleural Mesothelioma and Thymic Malignancies (ID 330)

    • Type: Science Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 4
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      SC06.01 - Comprehensive Genomic Analysis of Malignant Pleural Mesothelioma (ID 6621)

      14:30 - 15:45  |  Author(s): R. Bueno

      • Abstract
      • Presentation
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      Abstract not provided

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      SC06.02 - Stratified Therapy for Malignant Pleural Mesothelioma (ID 6622)

      14:30 - 15:45  |  Author(s): D.A. Fennell

      • Abstract
      • Presentation
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      Abstract not provided

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      SC06.03 - Intraoperative Therapies in Malignant Pleural Mesothelioma (ID 6623)

      14:30 - 15:45  |  Author(s): I. Opitz

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Intraoperative Therapies in Malignant Pleural Mesothelioma The rational of localized / intracavitary treatment is to eliminate microscopic residual disease (MRD) after macroscopic complete resection (MCR) for mesothelioma patients. The advantage of the treatment is that local effects can be enhanced whereas systemic side effects of the therapeutic agents applied might be reduced. Several approaches have been investigated over the past decades in preclinical and clinical trials, such as intracavitary chemotherapy (iCTX), immunotherapy (iIT), photodynamic therapy (PDT) and gene therapy (iGT). Intracavitary chemotherapy (iCTX) iCTX has been studied after mesothelioma resection, not only after extrapleural pneumonectomy (EPP) but also after (extended) pleurectomy/decortication ((e)P/D). The main therapeutic agent used is cisplatin. In some trials hyperthermia was additionally added with the aims to enhance the penetration of cisplatin into tissues and maximize its cytotoxicity in tumor cells [1]. Hyperthermic intrapleural perfusion had a maximum tolerated dose of 225-250 mg Cisplatin/m[2] BSA [2]. The morbidity ranges from 13 to 85% and the mortality from 0 to 29% [2, 3]. Some complications are related to renal toxicity which was the dose limiting adverse event [2]. Median survival time reaches up to 35.3 months in low-risk MPM patients receiving hyperthermic intraplueral cisplatin chemotherapy following MCR [4]. This treatment is only considered for well-designed clinical trials. In vivo preclinical model using intrapleural administration of cisplatin-mixed loaded to a fibrin carrier improved the local drug concentration and prolonged the exposure of tissue to high cisplatin concentration [5]. Our phase I dose escalation trial (INFLuenCe – Meso; see figure) has proven the safety of this treatment approach (manuscript in preparation). This treatment regimen is now being tested in a phase II trial (NCT01644994). Figure 1 In addition to chemotherapy, other substances have also been tested for intracavitary treatment. Recently, Tada, et. al. reported study plan for a phase I trial for intrapleural treatment with zoledronic acid, a third generation of bisphosphonates, in inoperable MPM, after having successfully proven the efficacy of zoledronic in a pre-clinical model [6]. Intracavitary immunotherapy (iIT) MPM is not a classical “immunogenic” tumor. Intrapleural instillation of cytokines such as interleukin (IL)-2, interferon (IFN)-α and IFN-γ provided a good control of malignant pleural effusion (MPE) and MPM with minimal toxicity [7, 8]. To prolong and increase local exposure of IFNs, recent studies implemented immuno-gene therapy approach using adenoviral vector expressing human IFNs. Four out of 10 patients with MPM and metastatic pleural effusions showed stable disease following a single dose of intrapleural adenoviral vector expressing IFN-β [9]. Nevertheless due to rapid production of neutralizing antibody against adenovirus, no improvement of gene transfer efficacy was achieved after the second dose [10]. The same research group conducted a clinical trial assessing the safety of adenoviral-mediated IFN-α2b in combination with chemotherapy. Recent data from this trial showed that the treatment is well tolerated and 25% of patients had partial response [11]. An intrapleural treament with re-directed T cells genetically engineered to express chimeric antigen receptor (CAR) that specifically recognizes tumor antigens is an attractive therapeutic option. A clinical phase I trial for intrapleural administration of fibroblast activation protein (FAP)-specific re-directed T cells is currently being conducted (NCT01722149). Photodynamic therapy (PDT) PDT is a light based cancer therapy. Most modern PDT applications involve three key components: a photosensitizer, a light source and tissue oxygen. The photosensitizing agent accumulates in tumor cells and is activated by light of a specific wavelength to produce reactive singlet oxygen that mediates cellular toxicity. The tumor cells are killed through both apoptosis and necrosis and by damaging tumor vasculature. It may also induce inflammatory reaction capable of stimulating a tumor directed host immune response. The advantages of this treatment are that its efficacy is not influenced by chemo- or radio-resistance of tumor cells, that it can be repeated at the same site without compromising its efficacy and that it does not compromise the ability to administer other treatment modalities in patients with recurrent or residual disease. PDT should be combined with macroscopic complete resection due to limited depth of penetration. Localized inflammation and fluid accumulation after treatment can modestly extend hospital stay. PDT appears promising and may improve local control and potentially prolong survival in properly selected patients who are able to undergo MCR, with clinical outcomes appearing best when PDT is combined with lung-sparing definitive surgery [12]. Friedberg reported a median survival of 31.7 months (41.2 months in patients with epithelioid histological subtype), but the progression free survival was only 9.6 months [13]. Intracavitary gene therapy (iGT) Gene therapy is based upon transfer of genetic material, including complementary DNA, full-lengths genes, small interfering RNA or oligonucleotids into cells for therapeutic purposes. For sufficient gene delivery, adenovirus is the most widely used in clinical trials among a variety of viral and non-viral vectors. In addition to delivering cytokine expressing vectors or re-directed T cells (see iIT part), several different cancer gene therapy approaches are currently used including the so called suicide gene therapy wherein a neoplasm is transduced with a cDNA encoding for an enzyme rendering tumor cells sensitive to a benign agent by converting the product to a toxic metabolite. The Herpes Simplex Virus 1- thymidine kinase (HSVtk) gene encodes for an enzyme that converts ganciclovir, an antiviral drug, to its cytotoxic metabolite. Intrapleural adenovirus HSVtk/ganciclovir administration was safe in MPM and two patients survived >6.5 years. Nevertheless, due to the fact that transgenes HSVtk were only detected at the surface of tumor tissues, the authors suggested that the treatment efficacy may be a result of antitumor immune response stimulation [14]. MPM tumor genome is characterized by frequent mutations in tumor suppressor genes such NF2, BAP1 or p53, thus the delivery of tumor suppressor gene expressing vectors into tumor cells can serve as an attractive treatment approach. The delivery of adenovirus expressing p53 has been tested in clinical trials for lung cancer but did not show better clinical benefit over chemotherapy [15]. This may be due to limited transfection efficiency of the vector and the stimulation of neutralizing antibody, therefore an improvement of transfection is still needed for the further development of gene therapy. References: 1. Sugarbaker, P.H., et al., Update on chemotherapeutic agents utilized for perioperative intraperitoneal chemotherapy. Oncologist, 2005. 10(2): p. 112-22. 2. Richards, W.G., et al., Phase I to II Study of Pleurectomy/Decortication and Intraoperative Intracavitary Hyperthermic Cisplatin Lavage for Mesothelioma. J Clin Oncol, 2006. 24(10): p. 1561-1567. 3. de Bree, E., et al., Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma. Chest, 2002. 121(2): p. 480-7. 4. Sugarbaker, D.J., et al., Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection. J Thorac Cardiovasc Surg, 2013. 145(4): p. 955-63. 5. Lardinois, D., et al., Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma. J Thorac Cardiovasc Surg, 2006. 131(3): p. 697-703. 6. Tada, Y., et al., An intrapleural administration of zoledronic acid for inoperable malignant mesothelioma patients: a phase I clinical study protocol. Springerplus, 2016. 5: p. 195. 7. Astoul, P., et al., Intrapleural recombinant IL-2 in passive immunotherapy for malignant pleural effusion. Chest, 1993. 103(1): p. 209-13. 8. Antoniou, K.M., E. Ferdoutsis, and D. Bouros, Interferons and their application in the diseases of the lung. Chest, 2003. 123(1): p. 209-16. 9. Sterman, D.H., et al., A phase I clinical trial of single-dose intrapleural IFN-beta gene transfer for malignant pleural mesothelioma and metastatic pleural effusions: high rate of antitumor immune responses. Clin Cancer Res, 2007. 13(15 Pt 1): p. 4456-66. 10. Sterman, D.H., et al., A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions. Mol Ther, 2010. 18(4): p. 852-60. 11. Sterman, D.H., et al., Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNalpha Combined with Chemotherapy. Clin Cancer Res, 2016. 22(15): p. 3791-800. 12. Simone, C.B., 2nd and K.A. Cengel, Photodynamic therapy for lung cancer and malignant pleural mesothelioma. Semin Oncol, 2014. 41(6): p. 820-30. 13. Friedberg, J.S., et al., Radical pleurectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma. Ann Thorac Surg, 2012. 93(5): p. 1658-65; discussion 1665-7. 14. Sterman, D.H., et al., Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy. Clin Cancer Res, 2005. 11(20): p. 7444-7453. 15. Schuler, M., et al., Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study. J Clin Oncol, 2001. 19(6): p. 1750-8.



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      SC06.04 - Immunotherapy of Malignant Pleural Mesothelioma and Thymic Malignancies: The End of the Beginning? (ID 6624)

      14:30 - 15:45  |  Author(s): J.P. Van Meerbeeck

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The significant improvement in outcome observed with immune checkpoint inhibitors in advanced melanoma and NSCLC have triggered their use in mesothelioma and thymic tumours. Both tumours are characterized by an unmet need to improve their prognosis and an immunosuppressive environment induced by (i) the (over-)expression of checkpoint receptors, responsible for controlling and inactivating the immune system in order to avoid autoimmunity and prevent collateral tissue damage- and (ii) by a silencing of the antigen presenting function of dendritic cells by tumor-derived soluble factors, leading to a defective induction of cytotoxic T–lymphocytes response [1]. The new paradigm consists of reactivating these silenced immune responses by either monoclonal antibodies or cell-based therapies. CTLA-4 is responsible for modulating central T-cell activation in the lymph nodes. Under physiological conditions, the immune inhibitory effect of CTLA-4 is involved in provoking an effective immune response without causing excessive damage to the normal surrounding tissue. However, tumor cells can stimulate abnormal expression of CTLA-4 by secreting TGF-beta, that induces CTLA-4 overexpression, resulting in a state of T-cell dysfunction whereby T-cells fail to proliferate and are no longer able to exert their effector functions. Tremelimumab and ipilimumab are selective monoclonal antibodies against CTL-A4 and block its binding to CD80 and CD 86, thereby enhancing T cell activity and anti tumor immunity. There are no known predictive factors for anti-CTL-A4 therapy in mesothelioma. After 2 phase 2 trials at different dose levels –which were negative for their primary endpoint, but nevertheless considered promising- DETERMINE compared tremelimumab to placebo as second line treatment in MPM [2]. No difference in outcome was reported, but an increased class specific toxicity in the patients treated with tremelimumab. The PD-1-PD-L1 axis is responsible for controlling peripheral T-cell activation at the tumor site. Overexpression of PD-L1 is thought to induce immune tolerance. In MPM, PD-L1 expression by immunohistochemistry was reported in 20-70% of formalin-fixed paraffin embedded mesothelioma, in 70% of thymic carcinomas and in 23% of thymomas [1,3]. In mesothelioma, PD-L1 expression overexpression is more common in non-epitheloid histology, is associated with a significantly worse survival. PD-L1 expression is furthermore considered a –weak- predictive factor for the activity of immune checkpoint inhibitors in NSCLC, besides mutagenic load and the formation of neo-epitopes. Several anti PD-(L)1 antibodies are registered and/or in development for use in other tumour types. Promising phase 2 trial results in mostly pretreated mesothelioma patients are summarized in the table [4-6]. Expression level of PD-L1 did not correlate with response in either trial.

      Checkpoint inhibitors in mesothelioma
      Trial Drug Phase Line N Subtype ORR/DCR (%) PFS
      DETERMINE (2) Tremelimumab 3 2/3 382 Ep: 83% 4.5/31.7 2.8 m
      KEYNOTE 28 (4) Pembrolizumab 2 2 25 all PDL1+ 28/76 49.4% @ 6m
      NIVOMES (5) Nivolumab 2 NR 18 NR 27/49 NR
      JAVELIN (6) Avelumab 1b 2-5 53 Ep: 83% 9.4/56.6 17.1 w
      Dendritic cells (DC), obtained by leukapheresis, can be loaded with synthetic peptides coding for parts of tumor-associated antigens, a lysate of tumor material of the patient itself (autologous dendritic cell-therapy) or with other sources of tumor-specific antigens (allogeneic dendritic cell-therapy). Wilms' tumor 1 (WT1) is an ideal candidate for a tumor selective cancer vaccine in cancers expressing WT1, such as MPM. Two vaccines have investigated this approach. Vaccination with autologous DC’s, electroporated with mRNA encoding the WT1 antigen was evaluated in 10 patients with mesothelioma not progressing after platinum/ pemetrexed-based chemotherapy [7]. Biweekly intradermal vaccinations were administered for an intended period of 6 months, followed by monthly or bimonthly injections. DC vaccination was well-tolerated: no systemic toxicity was recorded; local reactions at the injections sites occurred in all patients, but were mild and self-limiting. At a median follow-up of 22.7 months, 6 patients are alive, 4 have died and 1 year survival rate is 90% from start of treatment, suggesting that adjuvant DC-based immunotherapy provides a clinical benefit. In a pilot trial in pretreated MPM, the multivalent native and synthetic WT1 peptide vaccine Galinpepimut-S was well-tolerated and CD4/8 immune responses were generated. After completing multimodality therapy, 40 mesothelioma patients were randomized to receive maintenance Montanide and GM-CSF with or without Galinpepimut-S [8]. There were no serious treatment related adverse events. Based on a pre-specified futility analysis, accrual was stopped. Median PFS from randomization was 11.4 months in the experimental arm vs. 5.7 months in the control arm (HR 0.69). Similarly, median overall survival (OS) from randomization was 21.4 months in the Galinpepimut-S arm vs. 16.6 months in the control arm (HR 0.52). In the subgroup with R0 resection, median OS was 39.3 months in the Galinpepimut-S and 24.8 in the control arm (p = 0.04). A confirmatory adequately powered randomized adjuvant study is awaited. In the European DENIM trial, patients not progressing after 1[st] line platinum-pemetrexed chemotherapy will be randomized between standard follow up and a maintenance treatment consisting of 5 injections of DC’s, pulsed with an allogeneic lysate obtained from 5 well-characterized clinical grade human malignant mesothelioma cell lines. Cell-based immunotherapy carries high expectations but remains cumbersome and labour-intensive. Anti-CTL-A4 antibody-based immunotherapy in mesothelioma has so far failed to deliver the expected improvement in outcome. Whether this also applies to anti-PD-(L)1 monoclonal antibodies remains to be seen from ongoing and future trials. A low mutational burden and the limited formation of neo-epitopes under chemotherapy, -both considered important predictive factors for immune checkpoint therapy- are the challenges for this approach. As in other tumour types, studying a combination of different checkpoint inhibitors either with or without chemotherapy or with anti-angiogenic agents is of interest [9]. In thymic tumours, the presence or risk of developing immune-mediated paraneoplastic syndromes is of particular concern. This could be an argument to prioritize checkpoint inhibitors in thymic carcinomas[10]. References 1: Marcq E et al. Targeting immune checkpoints: new opportunity for mesothelioma treatment? Cancer Treatm Rev 2015; 41(10):914 2:Kindler HL et al.. Tremelimumab as second- or third-line treatment of unresectable malignant mesothelioma (MM): Results from the global, double-blind, placebo-controlled DETERMINE study. J Clin Oncol 2016; 34 (suppl): abstr 8502 3: Katsuya Y et al. Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma. Lung Cancer. 2015;88(2):154 4: Alley EW et al. Single-Agent Pembrolizumab for Patients with Malignant Pleural Mesothelioma. J Thorac Oncol 2015; 10(9) supplement 2: abstr O11.03 5: Quispel-Janssen J et al. NIVOLUMAB IN MALIGNANT PLEURAL MESOTHELIOMA (NIVOMES): AN INTERIM ANALYSIS. Proc IMiG 13, Birmingham 2016; abstr MS 04.07 6: Hassan R et al. Avelumab in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase Ib trial: safety, clinical activity and PD-L1 expression. J Clin Oncol 2016; 34(suppl): abstr 8503 7: Berneman ZN et al. Dendritic cell vaccination in malignant pleural mesothelioma: A phase I/II study. J Clin Oncol 2014; 32:5s: abstr 7583 8: Zauderer MG et al. Randomized phase II study of adjuvant WT1 vaccine (SLS-001) for malignant pleural mesothelioma after multimodality therapy. J Clin Oncol 2016; 34 (suppl): abstr 8519 9: Anonymous. Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients (MAPS2). Available at: https://clinicaltrials.gov/ct2/show/NCT02716272 10: Anonymous. MK-3475 in Patients With Thymic Carcinoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02364076

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    ED05 - The 8th Edition of the TNM Staging System (ID 268)

    • Type: Education Session
    • Track: Radiology/Staging/Screening
    • Presentations: 4
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      ED05.01 - What’s New in Lung Cancer Staging? (ID 6443)

      16:00 - 17:30  |  Author(s): H. Asamura

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The tumor, node and metastasis (TNM) classification for malignant tumors has been periodically revised in the International Union for Cancer Control (UICC) and American Joint Committee on Cancer (AJCC). As for lung cancer, the process of revision is quite unique compared with malignancies of other organs in that the corresponding professional society, the International Association for the Study of Lung Cancer (IASLC), has been playing a principal role in database construction, making revision agenda, simulation, and validation as a proposal to UICC and AJCC. The agenda articles have been already published for T, N, M, and stage grouping in the official journal of IASLC. In brief, the IASLC database included 77,156 evaluable patients diagnosed with lung cancer from 1999 to 2010, originating from 35 different databases in 16 countries of 5 continents. Among these, the data of 3905 patients were given by electric data capturing. In the T descriptors, new tumor-size groups were created: T1a 1-2 cm; T1c >2-3cm; T2a >3-4cm; T2b >4-5cm; T3 >5-7cm; and T4 >7cm. Endobronchial l ocation <2cm from the carina has better prognosis than any other T3 descriptor and will be classified as T2. Total atelectasis/pneumonitis will be classified as T2 because it has a T2 prognosis. Diaphramatic invasion will be T4. Visceral pleural invasion remains the same, and mediastinal pleura invasion, seldom used, disappears as a T descriptor. The N component remains the same, but the number of involved nodal stations has prognostic impact. Therefore, it was proposed to divide N1 into N1a (single station N1) and N1b (multiple station N1), N2 into N2a1 (single station N2 without pN1 involvement), N2a2 (single station N2 with pN1 involvement) and N2b (multiple station N2) for testing. For the M component, M1a (intrathoracic metastases) remains the same, but extrathoracic metastases are divided into single extrathoracic metastasis (new M1b) and multiple extrathoracic metastases in a single or multiple organs (M1c). Regarding stages, stage IA is divided into IA1, IA2 and IA3 to accommodate T1a, T1b and T1cN0M0 tumors; all N1 disease are stage IIB except for T3-T4N1M0 that are IIIA; a new stage IIIC is created for T3-T4N3M0 tumors; and stage IV is divided into IVA (M1a and M1b) and IVB (M1c). The 8[th] edition of the TNM classification of lung cancer defines new tumor-size groups, confirms the prognostic relevance of quantifying nodal disease, establishes a new category for single extrathoracic metastasis, and creates new stage groupings. Looking at these, the importance of the accurate measurement of tumor diameter and accurate counting of the swollen nodes and lesions of distant disease has been raised. In this way it improves our understanding of the anatomic extent of the tumor, enhances ,our capacity to indicate prognosis at clinical and pathologic staging, and increases the possibilities of research by facilitating tumor stratification for future clinical trials.

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      ED05.02 - Update on the Mesothelioma Staging System (ID 6444)

      16:00 - 17:30  |  Author(s): V. Rusch

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The initial TNM staging classification for malignant pleural mesothelioma (MPM), published in the 6th edition of the UICC and AJCC staging manuals, was derived from analyses of small retrospective surgical series. It has been criticized for being insufficiently evidence-based and difficult to apply to clinical staging. To identify potential deficits in the MPM staging classification, the IASLC Staging and Prognostic Factors Committee (ISPC), in collaboration with members of the International Mesothelioma Interest Group (IMIG), initiated a large multinational database in 2009. This approach was modeled on methods used by the IASLC to revise the lung cancer staging system. Data were submitted on 3,101 patients from 15 centers on 4 continents, all of whom had some form of surgical management, and an initial analysis was published in 2012. Overall survival (OS) data largely supported continued use of the original MPM staging classification but identified several important areas for improvement, particularly for the T and N components. To address issues raised by this initial analysis, a second iteration of the IASLC MPM database was started in 2013 to inform revisions for the 8th edition of the AJCC / UICC staging systems. The data dictionary was revised to provide more granular information for the T, N and M descriptors and a new electronic data capture (EDC), housed at the biostatistical center CRAB (Cancer Research and Biostatistics, Seattle, WA, USA), was developed. Additional investigators who could provide valid information on patients with tumors staged clinically and managed non-surgically were recruited. Data to inform revisions for the 8th edition of the MPM staging classification originated from 29 centers on 4 continents and included 3,519 cases of which 2,460 passed the initial eligibility screen. As planned, this dataset included both patients managed surgically and non-surgically. OS examined for T categories according to the current 7th edition staging classification showed a clear difference between all clinically staged categories except for T1a versus T1b and T3 versus T4. Pathological staging failed to demonstrate a survival difference between adjacent categories with the exception of T3 versus T4. Performance improved with collapse of T1a and T1b into a single T1 category. Analyses suggested that all current T descriptors should be maintained. Tumor thickness and morphology were also significantly associated with OS. Consequently, a recommendation was made to collapse both clinical and pathological T1a and T1b into a T1 category. Because simple measurement of pleural thickness had prognostic significance, it was felt that this should be examined further with a view to incorporation into future revisions of the staging classification. With respect to the N categories (as defined in the 7th edition staging classification), there was no significant difference in OS between cN0, cN1 and cN2, likely reflecting the inaccuracies of current methods for clinical lymph node staging in MPM. For pathologically staged tumors, patients with pN1 or pN2 tumors had a worse OS than those with pN0 tumors but no OS difference was noted between those with pN1 and pN2. Exploratory analyses found that tumors with both pN1 and pN2 nodal involvement had a poorer OS than those with pN2 only. Consequently, a recommendation was made to collapse N1 and N2 into a new N1 category and to relabel the current N3 category as N2. Larger numbers of well staged cases are needed to determine whether this new N1 category should be subdivided in the future according to the number of involved lymph node stations. Of the 3,519 submitted cases, 84 were cM1 at diagnosis. Median OS for cM1 was significantly worse than for T4 or N3 (as defined in the 7th edition) supporting inclusion of only cM1 in the stage IV group. Exploratory analyses suggested a possible difference in OS for single versus multiple site cM1 but additional data are needed in the future to determine the validity of this finding. Candidate stage groups were developed using a recursive partitioning and amalgamation (RPA) algorithm applied to all cM0 cases. Based on these analyses, optimal stage groupings proposed for the 8th edition of the staging classification were: stage IA (T1N0), stage IB (T2-3N0), stage II (T1-2N1), stage IIIA (T3N1), stage IIIB (T1-3N2 or any T4) and stage IV (any M1). These new stage groupings are substantially different from what is currently used in the 7th edition. The IASLC database is the largest available multinational database in this rare malignancy and has provided the first evidence-based revisions of the TNM classification for MPM leading to substantial changes in the T and N components and the stage groupings. Continued efforts to accrue to this database will be important to inform further changes for the 9th edition of the staging classification.[1-7] Reference List (1) Rusch VW, The International Mesothelioma Interest Group. A proposed new international TNM staging system for malignant pleural mesothelioma. Chest 1995;108:1122-8. (2) Rusch VW, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Initial analysis of the International Association for the Study of Lung Cancer Mesothelioma Database. J Thorac Oncol 2012;7:1631-9. (3) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. Supplementary prognostic variables for pleural mesothelioma: A report from the IASLC Staging Committee. J Thorac Oncol 2014;9(6):856-64. (4) Pass HI, Giroux D, Kennedy C, Ruffini E, Cangir AK, Rice D, et al. The IASLC Mesothelioma Database: Improving staging of a rare disease through international participation. J Thorac Oncol. In press 2016. (5) Nowak AK, Chansky K, Rice DC, Pass HI, Kindler HL, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for mesothelioma. J Thorac Oncol. In press 2016. (6) Rice DC, Chansky K, Nowak AK, Pass HI, Kindler HL, Shemanski L, et al. The IASLC Mesothelioma Staging Project: Proposals for revisions of the N descriptors in the forthcoming eighth edition of the TNM classification for malignant pleural mesothelioma. J Thorac Oncol. In press 2016. (7) Rusch VW, Chansky K, Kindler HL, Nowak A, Pass HI, Rice DC, et al. The IASLC Malignant Mesothelioma Staging Project: Proposals for the M descriptors and for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for mesothelioma. J Thorac Oncol. In press 2016.

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      ED05.03 - The Thymic Epithelial Tumor Staging System (ID 6445)

      16:00 - 17:30  |  Author(s): K. Kondo

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Thymic epithelial tumors are rare tumors. The clinical staging system for thymoma was introduced first by Bergh and associates in 1978 and later modified by Wilkins and Castleman (1), and was almost established by Masaoka and associates in 1981 (2). In France, multiple centers have adopted the Groupe d’Etudes des Tumeurs Thymiques (GETT) staging system (1). The Masaoka classification is the most widely accepted now and is an excellent predictor of the prognosis of thymoma (3, 4). And a modification of this classification was suggested by Koga et al. in 1994 (5) The International Thymic Malignancies Interest Group (ITMIG) has chosen to use the Masaoka-Koga stage classification system (1). There has never been an official TNM system classification of thymic epithelial tumor by American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage classification due to their relative rarity. Yamakawa and Masaoka presented a tentative TNM system classification of thymoma in 1991. Then Tsuchiya et al. (1994) in National Cancer Center Hospital of Japan, the WHO (2004) and Bedini et al.(2005) in National Cancer Institute of Italy proposed a TNM staging system (1). The ITMIG and the International Association for the Study of Lung Cancer (IASLC) simultaneously set out to accomplish a staging system for thymic epithelial neoplasms, and subsequently joined forces in 2010, partnering to create a Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC), charged with the development of proposals to AJCC/UICC for the eight edition of the stage classification system. The ITMIG and IASLC assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. They made a stage classification that was tumor, node, metastasis (TNM) based, and applicable to thymoma as well as thymic carcinoma (6-9) (Tables). The T component is divided into 4 categories (Table 1). A tumor is classified in a particular “level” if one or more structures in that level is involved, regardless of whether other structures of a lower level are involved or not. The encapsulation of the tumor is not included, because this did not have a clinically significant difference of prognosis in the retrospective database. The T1 includes tumors that were classified as stage I or II in the Masoaka or Masaoka-Koga stage classification systems. The involvement of the pericardium pathologically is designated as T2, and several neighboring organs (potentially resectable) are included in the T3 category because they had similar prognosis. The T4 includes several organs with more extensive local invasion (potentially unresectable). The TD-SPFC decided to subcategorize T1 into T1a (no mediastinal pleural involvement) and T1b (involvement of the mediastinal pleura) to gain more prospective data for further testing, as there is a slight difference in cumulative incidence of recurrence in patients from Japan submitted by the Japanese Association for Research in the Thymus (6, 7). Lymph node involvement is common in thymic carcinoma (more than 27%) but is relatively uncommon in thymoma (2%) (4). The N component is divided into 3 categories (Table 1). No lymph node metastasis is classified as N0. Lymph nodes are assigned in 2 groups according to their proximity to the thymus: anterior (perithymic) (N1) and deep cervical or thoracic nodes (N2). The anterior region (N1) encompasses the space surrounding the thymus that is bordered by the hyoid bone and diaphragm craniocaudally, the medial edge of the carotid sheaths and mediastinal pleura laterally, the sternum anteriorly, the pericardium and great vessels posteriorly in the middle, and extending to the level of the phrenic nerves posterolaterally. The deep region (N2) describes the space distant to the anterior region within the mediastinum. It is situated posterior to the anterior mediastinum, anterior to the esophagus, and among the pulmonary hila; it extends into the neck on either side of the anterior cervical nodes. Involved nodes outside these regions are outside the N category and considered a distant metastasis (M1) (6, 8, 9). The M component is divided into 3 categories (Table 1). Absence of tumor outside the primary mass (or nodal metastases) is classified as M0. M1a is used to designate pleural or pericardial nodules. M1b designates pulmonary intraparenchymal nodules or distant metastases (6, 8). The TNM categories are organized into distinct stage groups as shown in Table 2. Stages I, II, IIIa, and IIIb are determined primarily by the T component. Stages IVa and IVb are determined by the presence of N1 or M1a disease for IVa and N2 or M1b disease for IVb (6-9). Figure 1 Figure 2 References 1. Detterbeck FC, Nicholson AG, Kondo K, Van Schil P, Moran C. The Masaoka-Koga Stage Classification for Thymic Malignancies Clarification and Definition of Terms. J Thorac Oncol. 2011;6: S1710–S1716. 2. Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–92. 3. Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004;77:1860-9. 4. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878–84. 5. Koga K, Matsuno Y, Noguchi M, et al. A review of 79 thymomas: modification of staging system and rappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 1994;44:359–67. 6. Detterbeck FC, Stratton K, Giroux D, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposal for an Evidence-Based Stage Classification System for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S65–S72 7.Nicholson AG, Detterbeck FC, Marino M, et al.,,The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: Proposals for the T component for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S73–S80 8. Kondo K, Schil PV, Detterbeck FC, et al. The IASLC/ITMIG Thymic Epithelial Tumors Staging Project: Proposals for the N and M Components for the Forthcoming (8th) Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S81-S87 9. Bhora FY, Chen DJ, Detterbeck FD,et al., The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors. J Thorac Oncol. 2014;9: S88–S96





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      ED05.04 - What’s New in Esophageal Cancer Staging? (ID 6446)

      16:00 - 17:30  |  Author(s): T. Rice

      • Abstract
      • Presentation
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      Abstract:
      What’s New in Esophageal Cancer Staging? Thomas W. Rice, MD The 8th edition cancer staging manuals will be published later this year,[1,2] and the new staging recommendations will go into effect January 1, 2017. Staging cancer of the esophagus and esophagogastric junction for the 8th edition of the AJCC/UICC manuals was developed on a strong 7th edition foundation.[3,4] A greatly enhanced Worldwide Esophageal Cancer Collaboration (WECC) database, with a substantial increase in both numbers of patients (22,654) entered and variables (39) collected,[5-7 ]permitted a more dynamic and dependable Random Forest–based machine learning analysis. Random Forest analyses provided risk-adjusted survival estimates for all patients, from which distinctive and homogeneous stage groups with monotonically decreasing survival were identified.[8-10] Cancer Categories There were no major changes in cancer categories; however, there were some important refinements for T, N, grade, and location. Subcategorization of pT1 into pT1a and pT1b enhanced and improved Stage I grouping. Regional lymph nodes (N) were clarified in a new and simplified map. Undifferentiated cancers now require additional analyses to expose histopathologic cell type. If glandular origin can be determined, the cancer is staged as Grade 3 adenocarcinoma; if squamous origin can be determined or if the cancer remains undifferentiated after full analysis, it is staged as Grade 3 squamous cell carcinoma. Cancer location, not important for adenocarcinoma stage grouping, in conjunction with grade is necessary to subgroup only pT3N0M0 squamous cell carcinoma. The definition of the esophagogastric junction was revised; cancers involving the esophagogastric junction with epicenters 2 cm or less into the gastric cardia are staged as adenocarcinomas of the esophagus, while those with more than 2-cm involvement are staged as stomach cancers. Stage Groupings Pathologic Stage Grouping (pTNM) Historically, pathologic stage after esophagectomy alone has been the sole basis for all cancer staging, regardless of classification (c, yc, yp, r, and a). Today, pathologic stage has lost some of its clinical relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains important for early-stage cancers and as a key reference point. Dissimilar stage group composition and survival profiles necessitated separate staging groupings for adenocarcinoma and squamous cell carcinoma. Neoadjuvant Pathologic Stage Grouping (ypTNM) New to the 8th edition is stage grouping of patients with esophageal cancers who have had neoadjuvant therapy and pathologic review of the resection specimen (ypTNM). Drivers of this addition include absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories (ypT0N0-3M0 and ypTisN0-3M0), dissimilar stage group compositions, and markedly different survival profiles. Grade and location play no role in neoadjuvant pathologic stage grouping. The groupings are identical for both histopathologic cell types. Clinical Stage Grouping (cTNM) Also new to the 8th edition is clinical stage grouping (cTNM) prior to treatment decision. Clinical staging is done typically in the absence of complete histologic cancer data, because clinical TNM categories are typically defined by imaging and examination of needle aspiration and biopsy specimens. Dissimilar stage group composition and survival profiles necessitated clinical stage grouping (cTNM) distinct from pathologic stage grouping (pTNM). There is separate clinical staging for adenocarcinoma and squamous cell carcinoma. How to proceed with TNM-8? 8th edition staging for cancer of the esophagus and esophagogastric junction are data driven and expanded from pathologic stage (pTNM) to include also pathologic stage after neoadjuvant therapy (ypTNM) and clinical stage (cTNM) before treatment decision. Critical evaluation of 8th edition staging, intensive data collection, in-depth analyses, and further consensus appraisal are necessary to proceed from the 8th to the 9th edition. References 1) American Joint Committee on Cancer Staging Manual. 8th ed. In press. 2) TNM classifications of malignant tumors. International Union Against Cancer. 8[th] ed. In press. 3) Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. American Joint Committee on Cancer Staging Manual. 7th ed. New York: Springer-Verlag; 2010. 4) Sobin LH, Gospodarrowicz MK, Wittekind C, editors. TNM classifications of malignant tumors. International Union Against Cancer. 7th ed. Oxford, England: Wiley-Blackwell; 2009. 5) Rice TW, Chen L-Q, Hofstetter WL, et al. Worldwide Esophageal Cancer Collaboration: pathologic staging data. Dis Esophagus. In press. 6) Rice TW, Lerut TEMR, Orringer MB, et al. Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data. Dis Esophagus. In press. 7) Rice TW, Apperson-Hansen C, DiPaola LM, et al. Worldwide Esophageal Cancer Collaboration: clinical staging data. Dis Esophagus. In press. 8) Rice TW, Ishwaran H, Hofstetter WL, Kelsen DP, Blackstone EH. Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. In press. 9) Rice TW, Ishwaran H, Kelsen DP, Hofstetter WL, Blackstone EH. Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. In press. 10)Rice TW, Ishwaran H, Blackstone EH, Hofstetter WL, Kelsen DP. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals. Dis Esophagus. In press.

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    ED06 - Symptom Management in Lung Cancer (ID 269)

    • Type: Education Session
    • Track: Palliative Care/Ethics
    • Presentations: 6
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      ED06.01 - Causes and Management of Dyspnea (ID 6447)

      16:00 - 17:30  |  Author(s): O. Burghuber

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      ED06.02 - Endobronchial and Pleural Palliation (ID 6448)

      16:00 - 17:30  |  Author(s): A. Valipour

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      Abstract not provided

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      ED06.03 - Pain Management (ID 6449)

      16:00 - 17:30  |  Author(s): V. Hirsh

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      Abstract:
      Introduction Pain is the most common symptom in cancer patients and it is also the most common symptom in lung cancer patients.[1]The majority of patients with lung cancer present with advanced stage of the disease at diagnosis. Symptoms may result from local effects of the tumor, from regional or distant spread or from distant effects not related to metastases-paraneoplastic syndromes. Pain in these patients may be associated with depression, fatigue [2] and may affect quality of life and patients’ performance status. Early palliative care including pain management may increase their survival. [3] Pain can be classified by type of pain or according to the origin of the pain. The location or origin of the pain determines the type of pain, thoracic or extrathoracic. Pain Pain is often multifactorial in origin and needs to be addressed in each aspect. It can be acute or chronic. Acute pain can be caused by hemorrhage into a tumor, bone pain secondary to a pathological fracture, visceral pain, ie. from acute intestinal obstruction or perforation of a viscous. Its duration is limited and predictable. Chronic pain is differentiated by its longevity. It is estimated that approximately 75% of cancer patients live with chronic pain. [4] It must be approached with dual aim: relieving the pain as well as preventing further recurrences of pain. Pathophysiology of Pain Physiological pain is termed nociceptive pain due to the stimulation of the sensory nociceptors located in tissues when damaged. They are somatic, visceral, neuropathic and psychogenic pains. [5] Neuropathic pain is associated with a loss of opioid receptors in sensory afferents and an increased release of glutamate in the dorsal horn. The resultant hyperexcitability causes spontaneous pain and hyperalgesia and allodynia in areas adjacent to the nerve damage. There are three main causes of pain in patients with advanced lung cancer: Skeletal metastatic disease 34%, Pancoast tumor 31%, chest wall disease 21%. [6] Principles of Pain Management The World Health Organization analgesic ladder for cancer pain relief provides a stepwise approach to managing pain in cancer patients. [7] Step 1 includes paracetamol or non-steroidal anti-inflammatory drugs. Step 2- weak opioids, ie. codeine. Step 3- strong opioids, ie. morphine. Non-opioid and adjuvant treatments can be added to steps 2 and 3. Different routes of the administration of analgesics and their side effects management will be described. Their advantages and disadvantages of each route of administration will be pointed out. The need of adjuvant treatments such as tricyclic antidepressants and anticonvulsants, corticosteroids, topical analgesics, treatments of nausea, constipation, etc., are an integral part of pain management. Interventional procedures help reduce the doses of analgesics and their side effects. [8] Special mention will be about skeletal metastases and bone targeted agents such as zoledronic acid and denosumab, which have shown ability to reduce the pain and analgesic consumption in lung cancer patients. [9] Complementary therapies which help to control pain will also be mentioned.ie. Acupuncture,[10] psychological methods of care, etc. Conclusion An active multidisciplinary approach is required to manage pain in patients with advanced lung cancer. Multifactorial pain is frequent and may require several different analgesics, along with general palliative care and even special interventional procedures. Patients with advanced lung cancer live longer as there are more treatment options. It is of utmost importance to preserve a good quality of life with a better performance status to enable them to receive now further available therapies. [1] Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. Pain. 1999;82 (32) :263-74. [2] Laird BJ, Scott AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J. Pain Symptom Manage. 2011;42(1): 1-11. [3] Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [4] Ferrell BR, Juarez G. Borneman T. Use of routine and breakthrough analgesia in care. Oncol Nurs Forum. 1999;26(10):1655-61. [5] Portenoy RK, Lesage P. Management of cancer pain. Lancet. 1999;353 (9165):1695-700. [6] Watson PN, Evans RJ. Intractable pain with lung cancer. Pain. 1987; 29(2):163-73. [7] Geneva W. World Health Organisation. Cancer Pain Relief. 1996 [8] Vranken JH, Zuurmond WW, de Lange JJ. Continuous brachial plexus block as treatment for the Pancoast syndrome. Clin J Pain . 2000;16(4):327-33 [9] Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patient with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21(16):3150-7. [10] Cassileth BR, Deng GE, Gomez JE, Johnstone PA, Kumar N, Vickers AJ. Complementary therapies and integrative oncology in lung cancer. ACCP evidence-based clinical practice guidelines (2[nd] edition). Chest. 2007;132(Suppl3):340S-54.

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      ED06.04 - Biology and Management of Tumor Cachexia (ID 6450)

      16:00 - 17:30  |  Author(s): J. Crawford

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      Abstract:
      The International Consensus Conference definition of cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass with or without fat mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.[1] As clinicians, we define cachexia clinically based on weight loss of 5% or greater or body mass index <20 kg/m[2], with 2% weight loss. On physical exam, we recognize cachexia based on gross loss of muscle mass and weakness, often associated with physical findings such as temporal wasting. However, these patients with physical stigmata of cachexia are a small subgroup of the total population. If one assesses objective measures of muscle mass, approximately half of patients with advanced lung cancer will have muscle wasting at diagnosis and 2/3 of patients will develop it during their treatment course. This muscle wasting or sarcopenia, occurs across all weight groups, including those with normal weight, overweight and obesity.[2] These patients would not be recognized clinically to be cachetic. Yet, they have significant clinical consequences from muscle wasting. The use of standardized CT for the quantitative assessment of skeletal muscle and other body tissues has helped us better understand the importance of muscle and its impact on cancer outcomes.[3] Muscle wasting is associated with an increased risk of dose limiting chemotherapy toxicity, shorter time to disease progression and reduced overall survival. Clinically, the cancer patient with cachexia undergoes a progressive decline in muscle mass with associated anorexia, fatigue and reduced quality of life. Patient reported outcomes include weakness, declining muscle strength, reduced mobility and impact on physical performance. At a molecular level, this loss of muscle mass is associated with a number of biochemical changes in enzymes, regulatory proteins, altered metabolism, increased markers of inflammation and impaired immunity. The driving force for muscle wasting in cancer patients is the competition for nutrients between the cancer and the host often complicated by decreased protein/caloric intake. However, the mechanisms that both incite and promote the ongoing process of muscle loss are complex and include factors associated with direct muscle atrophy, including the release of cytokines such as tumor necrosis alpha and interleukin 6, as well as myostatin and activin. One strategy that might ameliorate the cachexia process include therapeutic approaches that block these cytokine mediated pathways and several agents are in development.[4] Another approach has been to try to increase muscle growth signaling through anabolic pathways such as selective androgen receptor modulators (SARM) and ghrelin minetics. A first in class SARM, enobosarm has shown promising results with improvement of muscle mass and physical function in patients with cachexia.[5] Subsequent phase III trials in patients with advanced lung cancer receiving chemotherapy have shown increase in muscle mass in the enobosarm treatment group versus placebo, but physical function testing using stair climb measurement were inconsistent.[6] Meanwhile, trials of anamorelin, a ghrelin receptor agonist have also demonstrated improvement in skeletal muscle mass. In phase III trials in patients with advanced lung cancer and cachexia, improvement in skeletal muscle mass has been seen along with positive effects on improved appetite and weight gain. Again, functional improvement as measured by hand grip strength was not observed.[7] It is not clear why there is a lack of association of these promising agents that increase muscle mass, with functional improvement. This may reflect issues regarding the patient population, the objective test being used, the duration of treatment or other factors. However, these phase III trials in advanced lung cancer represent an important step forward in our understanding of cachexia and possible therapeutic interventions. Currently, as we are moving forward with the development of new agents for cachexia, it is important for us to recognize the magnitude of the problem in our patients. Until CT imaging becomes a standard clinical technique for assessment of muscle mass, we need to rely on our standard clinical approaches of history and physical exam. Perhaps most importantly, is our documentation of the degree of weight loss in our patients as a routine measure at baseline and during treatment just as we assess other patient reported outcomes such as pain, fatigue and functional status. Incorporating weight loss along with body mass index can be a very powerful tool for predicting outcome and survival for our patients.[8] Moreover, it can help us address potential interventions that may be of benefit for them. While current pharmacologic interventions are of limited benefit, exercise and nutritional support are both important interventions for our patients, along with continuing monitoring of appetite, weight and functional performance during treatment.[9] Cancer treatment itself can be associated with an increase in muscle mass, particularly in patients whose tumors respond well to therapy. However, for those patients who progress through therapy, the toxicity of our treatment only compounds the ongoing cachexia process. Better cancer therapeutics combined with optimum supportive care remain the goal of management. 1. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. 2. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncology. 2008; 9(7):629-35. 3. Prado CM, Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr Opin Clin Nutr Metab Care. 2011;14:250–254. 4 Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. 5. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013 Apr;14(4):335-45. 6. Crawford J, Prado C, Johnston M, Gralla R, Taylor R, Hancock M, Dalton J. Study design and rationale for the phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER Trials). Cur Oncol Rep (2016) 18:37. 7. Temel JS, Currow DC, Fearon K, et al. Phase III trials of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2). J Clin Oncol 33, 2015 (suppl; abstr 9500) 8. Martin L, Senesse P, Gioulbasanis I, Antoun S, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015 Jan 1;33(1):90-9. 9. Crawford J. Clinical results in cachexia therapeutics. Current Opinion in Clinical Nutrition & Metabolic Care. 19(3):199-204, May 2016.

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      ED06.05 - Surgery for Symptom Relief (ID 6451)

      16:00 - 17:30  |  Author(s): S. Taghavi

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      ED06.06 - Decisions in Case of Intractable Symptoms (ID 6452)

      16:00 - 17:30  |  Author(s): J. Klastersky, B. Michel, I. Libert, A. Georgala, M. Obiols, F. Lewis, D. Lossignol

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      Abstract:
      Case report A 55-year-old lady was diagnosed with small cell lung cancer in late 2008. She had been a long-time cigarette smoker without, any other significant medical history. She was a housewife, deeply religious and dedicated mother to 2 children. As a first treatment for her cancer, she received radiotherapy on the right apex and mediastinum, concomitantly with chemotherapy (cisplatin plus etoposide), early in 2009. Six months later, she presented a very painful right shoulder and chest wall. Chemotherapy was resumed, with some improvement of the pain, but late in 2009, radiotherapy had to be administered to the chest for uncontrolled pain; oral etoposide was given without much benefit. The pain progressively increased and the patient was complaining of increasing shortness of breath. As the tumour was clearly progressing, in 2010, with further lung, bone and liver involvement, a decision was made to discontinue any specific oncological treatment. Both symptoms pain and dyspnea increased in intensity and became uncontrollable late in 2010; the patient and her family requested sedation at any cost. The patient was started on palliative sedation and died peacefully after 2 days; with her family present. Supportive and palliative treatments for pain Table 1 summarizes the time evolution of the patient and the corresponding interventions as far as analgesics and co-analgesics are concerned. Management of dyspnea over the course of her disease, the patient experienced progressive dyspnea which could be managed with oxygen, corticoids, benzodiazepines and bronchodilatating aerosols, as well as physical therapy and hypnosis. Dyspnea became major and beyond control the day prior to the last hospitalization and was a reason for accelerated sedation. Figure 1 Management of depression The patient had multiple reasons for being severely depressed: her mother was experiencing lung cancer at the same time ; the patient was concerned about becoming increasingly a burden for her family; she was aware of her worsening condition and realizing that her life would end soon; she was extremely anxious to have to die in intractable pain. The management of the patient’s depression included the following: monthly consultation with an onco-psychiatrist and weekly visits to a psychologist-social worker ; psychotropic drugs ; several sessions of hypnosis. Palliative sedation That the control of the patient’s pain and/or dyspnea might require palliative sedation has been discussed since 2010 (time of worsening of her symptoms) between the patient, her family and the caregivers. The patient and her family spoke openly about end-of-life issues, always emphasizing not to let the patient die in severe pain. After making the decision to resort to sedation in case of intractable symptoms, the patient and her family expressed a sense of relief that her suffering could and would be alleviated. When the patient expressed unbearable pain and dyspnea, the mobile nursing team started her on midazolam, scopolamine and methadone by sub-cutaneous route, with no clear-cut response; the patient was brought to the hospital, where the same medications were given intravenously, with the addition of haloperidol. No attempt to lift the sedation process (respite sedation) was made, according to the patient’s will. The patient was able to rest comfortably and died peacefully after 2 days, with her family at her side. Discussion In case of dyspnea due to lung cancer progression, corticosteroids, morphine and oxygen are used since many years ; novel options were introduced timidly during the last years. These new options include non-invasive ventilation, high-flow oxygen and rational use of medications usually prohibited in patients with respiratory distress, such as benzodiazepines, antidepressants and synthetic opioids [1]. The World Health Organization (WHO) scale for cancer-related pain proves to be an effective approach to pain management in cancer patients [2], and many variations based on it have been proposed [3]. However, these approaches represent pragmatic and empiric attitudes that are rarely evaluated in prospective studies. There is also a lack of consensus about the use of co-analgesia and other supportive approaches for refractory pain [5]; although pragmatic recommendations exist, a comprehensive algorithm for the management of refractory pain is still lacking. Based on the experience in our supportive care unit, we proposed a comprehensive model for the progressive management of pain in cancer patients (Figure 1). Finally, the approach to pain (or other symptoms) that is beyond medical control, fortunately a relatively rare situation, has not been clearly defined [6;7]. Palliative sedation or euthanasia is always an emotionally and ethically challenging event for all involved and implies to meet the needs of the patient and family but also those of the caregivers [8; 9; 10] and requires repeated and professional counselling with the patient and family as well as regular debriefing sessions with the medical and nursing teams. Although the decision to offer and provide palliative sedation or euthanasia (if requested by the patient and not illegal) is never easy, it should be seen, however, as the medical duty to safeguard the patient’s autonomy, the principle of individual freedom to make choices. Figure 2 References 1. Cabezón-Gutiérrez L, Khosravi-Shahi P, Custodio-Cabello S, Muñiz-González F, del Puerto Cano-Aguirre M, Alonso-Viteri S. Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease. Support Care Cancer 2016;24:4045-55 2. Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 2001; 93:247-57 3. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain 1995; 63:65-76 4. Swarm RA, Abernethy AP, Anghelescu DL, et al. Adult cancer pain. J Natl Compr Canc Netw 2010;8:1046-86 5. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid –induced hyperalgesia. Pain Physician 2011; 14:145-61 6. Council on Scientific Affairs, American Medical Association. Good care of the dying patient. JAMA 1996;275:474-8 7. Field MJ, Cassel CK, eds. Approaching death: improving care at the end of life. Washington DC: : National Academy Press, 1997 8. de Graeff A, Dean M. Palliative sedation therapy in the last weeks of life : a literature review and recommendations for standards. J Palliat Med 2007; 10:67-85 9. Olsen ML, Swetz KM, Mueller PS. Ethical decision-making with end-of-life care: palliative sedation and withholding or withdrawing life-sustaining treatments. Mayo Clinic Proc 2010;85:949-54 10. Lossignol D. End-of-life sedation: is there an alternative? Curr Opin Oncol. 2015;27(4): 358-64





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    IA04 - Interactive Session Target Delineation: Group I (Ticketed Session) (ID 290)

    • Type: Interactive Session
    • Track: Radiotherapy
    • Presentations: 1