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N. Ikeda



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    MO08 - NSCLC - Early Stage (ID 117)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO08.11 - The role of aggressive local therapy and prognostic factors in postoperative recurrent non-small cell lung cancer: Is oligorecurrence state potential curable disease? (ID 925)

      17:15 - 17:20  |  Author(s): N. Ikeda

      • Abstract
      • Presentation
      • Slides

      Background
      Non-small cell lung cancer (NSCLC) with postoperative recurrence (POR) is generally believed to have an incurable disease. However, several studies have indicated that only a limited number of distant recurrences (oligorecurrence) may benefit from local therapy to the distant site of disease. We investigated factors associated with postrecurrence survival (PRS) in recurrent NSCLC, and particularly the role of local therapy to the metastatic site.

      Methods
      From 2000 through 2009, a total of 1542 patients with NSCLC underwent complete surgical resection. Of those, we reviewed the records of 356 patients with POR.

      Results
      Type of POR included locoregional only in 114 (32%), distant in 242 (68%). Of the 242, there were 65 oligorecurrences. Initial recurrence therapy found local treatment for 68 (surgery 5, radiation 12, surgery with chemotherapy and/or radiation 12, chemoradiotherapy 39). Multivariate analysis demonstrated that older age (HR1.522), advanced stage (HR1.371), shorter disease-free interval (DFI; HR1.733), non-adenocarcinoma (HR1.442), systemic treatment (-) (HR1.481), EGFR-TKIs (-) (HR1.563), local treatment (-) (HR1.705) and bone metastases (HR2.140) had a significant association with poor PRS, and oligorecurrences state appeared as an independent PRS factor in patient with distant recurrence (HR1.836). Median PRS times were 36.3 months for 37 patients with DFI > 16 months and receiving local treatment, and 16.0 months for other (p<0.001) in all patients (Fig.1), and 36.5 months for 29 patients with DFI > 16 months and oligorecurrence, and 14.6 months for other (p<0.001) in patient with distant recurrence (Fig.2). There was no significant difference in survival for the patients with oligorecurrence according to whether or not receiving local treatment. Figure 1Figure 2

      Conclusion
      This study showed that local therapy improved PRS in patients with POR. Optimization of personalized systemic treatment depends on patient selection, and therapeutic strategy for adding an aggressive local treatment options based on a careful follow-up is important.

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    MO26 - Anatomical Pathology II (ID 129)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO26.11 - Proposal on incorporating Blood Vessel Invasion into the T classification parts as a practical staging system for stage I Non-small cell Lung Cancer (ID 842)

      11:30 - 11:35  |  Author(s): N. Ikeda

      • Abstract
      • Presentation
      • Slides

      Background
      We investigated blood vessel invasion (BVI) as a possible negative prognostic factor in patients with stage I non-small cell lung cancer (NSCLC) according to the 7[th] Edition of the TNM classification.

      Methods
      Between 1999 and 2007, a total of 694 consecutive patients with pathological stage I NSCLC underwent complete resection with systematic lymph node dissection at Tokyo Medical University Hospital. All sections of the specimens were stained by Elastica van Gieson to visualize elastic fibers and were examined to determine the prognostic symptoms of BVI. We statistically analyzed the association between BVI and clinicopathologic factors, as well as clinical outcomes.

      Results
      BVI was detected in 201 patients with stage I NSCLC (29.0%). The 5-year overall survival (OS) rates of the non-BVI and BVI patients were 90.5% and 66.0%, respectively (p < 0.0001). BVI was found to be a significant independent prognostic factor by multivariate survival analysis in stage IA and stage IB NSCLC (HR 2.591, p < 0.001; HR 2.347, p = 0.009, respectively). The 5-year OS rate of patients with BVI was significantly worse than that of patients without BVI in the T1a (94.5% vs 87.5%, p < 0.0001), T1b (82.7% vs 65.9%, p = 0.034), and T2a (90.9% vs 61.8%, p < 0.0001) subgroups.

      Conclusion
      We identified the presence of BVI as an independent poor prognostic factor in patients with stage I NSCLC. In the future revision of the TNM staging system, the routine use of elastic fiber stains in pathological evaluations of lung cancer for BVI determination might be recommended, and tumors with BVI should be upstaged to the higher current T staging.

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 3
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      P1.07-006 - Lung cancer resection in patients with chronic renal failure on hemodialysis (ID 2104)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The number of patients with malignant tumors receiving long-term hemodialysis (HD) has been increasing. Patients on HD who undergo surgery represent a high-risk group requiring careful perioperative management to avoid electrolyte imbalance and hemodynamic instability. This retrospective study analyzed the postoperative outcome in terms of complications and survival of a group of patients on HD who underwent pulmonary resection for non-small cell lung cancer.

      Methods
      Between January 1995 and March 2013, 10 patients (7 men, 3 women; median age, 71.5 years) with non-small cell lung cancer who were also receiving HD underwent radical pulmonary resection by open thoracotomy or video-assisted thoracic surgery at Tokyo Medical University Hospital. We retrospectively evaluated their postoperative clinical outcomes and survival results. Most patients had comorbidities, including cardiovascular disease (5), diabetes (3), and brain infarction (1). The distribution of clinical staging was IA in 2 cases, IB in 5, IIB in 1, and IIIA in 2. Procedures included 8 lobectomies and 2 segmentectomies. We performed 4 systematic lymph node dissections and 6 selective lymph node dissections.

      Results
      The median intraoperative time was 215.5 minutes (range, 101-308). The median blood loss was 55 mL (range, 0-478 mL). Blood transfusion was not necessary. There was no intraoperative mortality. There were major perioperative complications in 4 patients, including atrial fibrillation (3), cardiac failure (1), shunt failure (1), and pneumonia (1). The median length of hospital stay was 21 days (range, 11-47). Thoracic drainage removal was at 4.5 postoperative days (range, 3-9). Pathological staging was IA in 3 cases, IB in 2, IIA in 2, IIB in 1, and IIIA in 2. Two cases were upstaged from the preoperative period to the final period. Seven of the 10 patients are currently alive and recurrence-free. Two patients had mediastinal lymph node and lung recurrence. One patient died from mediastinal lymph node recurrence at 8 months after surgery, and the other patient died at 26 months after surgery from malignant lymphoma.

      Conclusion
      Patients with chronic renal failure on HD who undergo lung resection have a high rate of postoperative complications (40%). Surgical treatment remains one of the effective treatments for patients on HD with lung cancer.

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      P1.07-009 - Preoperative simulation and navigation using the combination of high-speed 3D-image analysis system and Robotic surgery increase the efficacy and accuracy in thoracic surgery (ID 980)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Previously, we reported the utility of the da Vinci[®] Surgical System (dVS: Intuitive Surgical, Inc., Sunnyvale, CA) for various types of anterior and middle mediastinal tumors in clinical practice. We evaluated the feasibility, safety and appropriate settings of this system for the surgical treatment of these tumors. One review reports about the importance of the appropriate settings according to tumor location in robot-assisted thoracic surgery (RATS), because no target always exists in the same location within the thoracic cavity. In this report, we evaluated the efficacy of a high-speed three-dimensional (3D) image analysis system (SYNAPSE VINCENT; Fuji Photo Film Co., Ltd.) for preoperative simulation and navigation during a RATS procedure.

      Methods
      In this study, a high-speed 3D-image analysis system was used to decide the best positioning of robotic-arms and instruments preoperatively. Moreover, this system has capable of detecting the tumor location and extracting surrounding tissues quickly, accurately and safely. Accurate and speedy set-up of the da Vinci S[® ]Surgical System was possible for this operation. Synapse Vincent facilitated determining the best positioning of robot arms and instruments, and was an excellent device for navigation in real time. All patients who underwent RATS in our institution provided written informed consent to receive robotic surgery using the dVS, and the institutional review committees of each institution gave their permission. In this report, a representative mediastinal tumor which was located in the upper thoracic cavity was selected to establish the merits of this procedure.

      Results
      The patient, a 38-year-old woman, had a posterior mediastinal tumor located at the upper level of Th 1 to 3. Accurate and speedy set-up of the dVS was capable on this operation. It was feasible to decide the best positioning of robot-arms and instruments, and excellent device for the navigation on real time. The total operation time was 270 minutes, the time of the dVS setting was 21 minutes, and the console time (the dVS working time) was 132 minutes. The amount of bleeding was 167 mL and the drainage time was 2 days after the operation and this patient had no complications. The pathological report revealed a schwannoma (85 × 42 × 20 mm) with no malignancy.

      Conclusion
      For the optimal performance of RATS, the positioning of all units and the locations of instrument ports need suitable directional setting. Preoperative simulation and navigation during of operation using SYNAPSE VINCENT for the RATS has efficacy for planning the setting, especially in deciding the points of instrument ports and the angle of robot arms, and very useful as a device of the navigation software and education use operating on it.

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      P1.07-037 - Clinical characteristics of completely resected lung cancer with combined pulmonary fibrosis and emphysema (ID 2525)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The occurrence of both emphysema and pulmonary fibrosis in the same patient has received increased attention as the syndrome of combined pulmonary fibrosis and emphysema (CPFE). Patients with CPFE show severely impaired DLCO, hypoxemia at exercise, characteristic computed tomography (CT) imaging feature, and high probability of lung cancer. However, the clinical characteristics of lung cancer patients with CPFE are not well known. The aim of this study is to identify clinical characteristics of completely resected lung cancer with CPFE.

      Methods
      A total of 559 consecutive patients who underwent complete surgical resection for lung cancer from January 2008 through December 2010 were reviewed. Based on preoperative chest HRCT findings, patients were categorized into three groups: those with normal lung (N) (except for lung cancer), emphysema without pulmonary fibrosis (E), and CPFE. The HRCT inclusion criteria of CPFE is as follows; 1) Presence of emphysema, defined as well-demarcated areas of decreased attenuation in comparison with contiguous normal lung and marginated by a very thin or no wall, and/or multiple bullae with upper zone predominance. 2) Presence of a diffuse parenchymal lung disease with significant pulmonary fibrosis, defined as reticular opacities with peripheral and basal predominance, honeycombing, architectural distortion and/or traction bronchiectasis or bronchiolectasis. Chest HRCT scans were reviewed separately by two thoracic surgeons and one radiologist. The clinical characteristics of patients with CPFE were compared with those of the other groups.

      Results
      This study cohort included 328 (58.7%) patients in N group, 136 (24.8%) patients in E group, and 95 (17.0%) patient in CPFE group, with median age of 67 years. The 3-year survival rates were 68.4% in CPFE group, 80.2% in E group, and 89.7% in N group (p < 0.001). CPFE group found a positive correlation with each of the following factors compared to N and E groups; > 67 years (p = 0.004), lymph node metastases (p = 0.033), male gender (p < 0.001), tumor size > 3cm (p < 0.001), vascular invasion (p < 0.001), non-adenocarcinoma (p < 0.001), pleural invasion (p < 0.001), elevated preoperative serum CEA level (p < 0.001). The frequency of patients presenting grade 2 or more severe postoperative complication under CTCAE or Clavien-Dindo classification was 28.4% for CPFE group, 24.3% for E group, and 14.9% for N group (p = 0.004), and respiratory complication was higher for CPFE group (22.1%) than N group (5.8%) and E group (11.8%) (p < 0.001).

      Conclusion
      Resected lung cancer patients with CPFE had some different clinical characteristics in comparison with those with emphysema. Intensive postoperative management and a strict follow-up are required because of higher rate of postoperative complications and aggressive malignant behavior in CPFE patients.

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    P1.10 - Poster Session 1 - Chemotherapy (ID 204)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.10-006 - Examination of recurrence predictors in cases receiving UFT as postoperative adjuvant chemotherapy for lung cancer (ID 658)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Although the 2012 version of the clinical practice guidelines for lung cancer published by the Japan Lung Cancer Society recommends performing a tegafur-uracil (UFT) compound drug therapy on cases of non-small cell lung cancer for stage 1A and 1B tumors measuring > 2 cm in diameter after surgery, we often encounter cases of recurrence. Therefore, we obtained data on T2a tumors (> 3 cm but < 5 cm in diameter) treated with UFT as postoperative adjuvant chemotherapy at our hospital and examined their recurrence predictors.

      Methods
      Among 2,724 cases of total surgical removal of non-small cell lung cancer performed between January 1997 and December 2007, we examined 168 cases with stage 1B T2a tumors treated with UFT to clarify the recurrence predictors in these cases. We examined age, sex, tumor diameter, vascular invasion, lymphatic involvement, pleural invasion, histologic degree of differentiation, tissue, and CEA.

      Results
      The age range was 38 to 85 years (median 66 years), and there were 108 men and 60 women. The 5-year recurrence-free survival rate was 72.7%. In cases of recurrence, the median time to recurrence was 662 days in 48 of the 168 cases (28.6%). On univariate analysis, vascular invasion (p < 0.001), male sex (p = 0.045), and non-differentiation (p < 0.002) were identified as significant recurrence predictors. On multivariate analysis, vascular invasion (p = 0.009) was found to be a significant recurrence predictors. Please confirm this part as the changes were made based on the original Japanese text.

      Conclusion
      It was inferred that vascular invasion is a primary recurrence predictor in cases receiving UFT as postoperative adjuvant chemotherapy. We need to consider a more careful follow-up during UFT administration as postoperative adjuvant chemotherapy in stage 1B T2a tumors.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-010 - Analytical Performance of the cobas EGFR Mutation Assay for Japanese Non-Small Cell Lung Cancer (ID 1101)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Patients’ EGFR mutation status prior to treatment impacts outcomes and, EGFR testing has been developed as a companion diagnostic; this relationship between therapeutic and diagnostic agents is known as personalized healthcare. Recently, it was reported that about half of patients may acquire resistance to EGFR-TKIs following therapy, mainly by appearance of EGFR mutations, such as T790M. Thus, it is important to assess EGFR mutation status before and during treatment to determine the most appropriate treatment regimens for patients. A number of PCR-based techniques are used in the assessment of EGFR mutations. In Japan, the “Scorpion-ARMS” therascreen® EGFR Rotor-Gene Q PCR Kitis (therascreen EGFR assay) the only available in vitro diagnostic (IVD) test. The cobas® EGFR Mutation Test (cobas EGFR assay) is the only FDA-approved kit for IVD testing in the US.In this study, we compared the performance of the cobas EGFR assay and the therascreen® EGFR assay using FFPE tissue specimens from NSCLC patients.

      Methods
      We extracted DNA from 149 FFPE tissues of NSCLC, according to the manufacturer’s instructions and performed a comparative study of cobas EGFR and therascreen EGFR methods.

      Results
      EGFR mutations were identified in 63 NSCLC specimens (42.3%) using the cobas EGFR assay and 61 samples (41.2%) using the therascreen EGFR assay. The concordance rate between the cobas EGFR assay and therascreen EGFR assays was 145/149 (97.3%). Only three discordants between these EGFR assays were observed. One T790M mutation in combination with an L858R mutation was identified by the cobas EGFR assay. No invalid assay results occurred with the cobas EGFR assay.

      Conclusion
      The cobas EGFR assay has two advantages. One is that the process is easily performed by stable methods. It takes only 8 hours, from tumor specimen to results generated using the semi-automated system. Thus, patients assessed using the cobas EGFR assay can begin the most appropriate treatment quickly. The other advantage is that only a very small amount of DNA (150 ng) is required to detect mutation status using the cobas EGFR assay. Our results show a high concordance rate (97.3%) of cobas EGFR with an existing IVD product, the therascreen EGFR assay. In this study, one double mutant, T790M in combination with L858R, was only identified by the cobas EGFR assay. The cobas EGFR assay appears to give the most accurate and appropriate results for NSCLC patients.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-029 - Clinical features and outcome of surgically resected secondary primary non-small cell lung cancer (ID 2607)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The incidence of a second primary lung cancer has been reported with 1-2% per patient year. Still, relatively few data has been published about this selected group of patients with sometimes conflicting results. Most data has been included low patient numbers that derived either from multiple institutions or from a long time period that may have rendered conclusions difficult caused by varying diagnostic procedures and therapeutic developments. Moreover, data regarding clinical characteristics is lacking for patients with first primary lung cancer who might be at risk for developing second primary lung cancer

      Methods
      From January 1999 to December 2008, 65 patients with second primary lung cancer, classified by the criteria proposed by Martini and Melamed, were treated at our Institution. We had 34 patients with a synchronous tumour and 31 with metachronous. As second treatment, we performed 11 lobectomies and 54 segmentectomies and widewedge resections. Histology was adenocarcinoma in 58, squamous in 4, adenosquamous in 8, large cells in 2 and pleomorphic in 1.

      Results
      Overall 5-year survival from second surgery was 69%; overall operative mortality was 0.65% (1 patient). Regarding the interval of surgery, the second operation had performed later than 2 years group showed a better 5-year survival than within 2 years group (80.6% and 69.2%, respectively, P = 0.008). Compared with lobectomies, segmentectomy showed a no significantly changes in survival rate(69 and 60%, respectively, P >0.051).

      Conclusion
      From our experience, lobectomy should still be considered as the treatment of choice in the management of second primary lung cancer, but sublobar resection remains a valid option in high-risk patients with limited pulmonary function.

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    P2.10 - Poster Session 2 - Chemotherapy (ID 207)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P2.10-019 - A prospective cohort study of non-squamous non-small cell lung cancer patients treated with bevacizumab (ID 1288)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      In several clinical trials, first line combination chemotherapies with bevacizumab (Bev) have been reported to improve clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). Although Bev was approved for NSCLC in autumn of 2009 in Japan, there are not enough data regarding the efficacy and toxicity with Bev treatment in real-world clinical practice in Japan. We have evaluated the efficacy and safety of the combination chemotherapy with Bev in patients with non-sq NSCLC at four major hospitals in Shinjuku area, Tokyo, Japan.

      Methods
      From August 2010 to July 2012, 102 patients planned to treat with Bev was prospectively enrolled in this study with written informed consent. Eligible patients were histlogically or cytologically documented non-sq NSCLC with advanced stage (IIIB-IV) or recurrence, ECOG-PS 0-2, and adequate organ function for cytotoxic chemotherapy. Patients received Bev (15mg/kg, every 3 weeks) plus any chemotherapy (physician’s choice) followed by maintenance Bev. The primary endpoints were safety and efficacy (PFS). Patients were treated at four major hospitals (three university hospitals and one national center) participating in Shinjuku Thoracic Oncology Group (STOG).

      Results
      Patients characteristics: median age (range) 64 (36-85) years, male/female = 60/42, clinical staging: IIIB/IV/post-operation recurrence/others ＝ 8/77/15/1, ECOG-PS 0/1/2 = 66/34/2, adenocarcinoma/others = 98/4, non-smoker/smoker = 40/60, EGFR mutation (+)/(-)/unknown ＝ 43/56/3, 1[st ]line /2[nd] line />=3[rd] line ＝ 56/23/23, Bev combination regimen: CBDCA+PEM/ CDDP+PEM/ CBDCA+PTX/ others ＝ 40/22/18/22. At the time of April 2013, median Bev administration number (range) was 7 (1-29) in total; 7.5 (1-29) in 1[st] line, 8 (1-24) in 2[nd] line, 7 (1-21) in >= 3[rd] line. With evaluable 102 cases, response rate (RR) was 39.2%, disease control rate (DCR) was 90.2%, median PFS was 321 (95%CI: 195-410) days (10.6 months (M)). Median overall survival was not reached. RR, DCR, and PFS were 46.4%, 96.4%, 10.9M with 1[st] line, 39.1%, 87.0%, 9.1M with 2[nd] line, 21.7%, 78.3%, 9.3M with >= 3[rd] line. Hematological toxicities (>=G3): leucocytopenia 24%, neutropenia 40%, anemia 8%, thrombocytopenia 5%, febrile neutropenia 3%. Bev related adverse events (>=G3): Hypertension 28%, proteinuria 5%, thromboembolism 5%, hemosputum 1%. There was no treatment related death.

      Conclusion
      Combination chemotherapy with Bev was effective for the patients with non-sq NSCLC in real-world clinical practice in Japan, as similar or superior efficacy as clinical trials. Also, adverse events were well tolerated. The efficacy was good at 1[st] line and also at 2[nd] line and thereafter.

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      P2.10-048 - Therapeutic efficacy of gefitinib for postoperative recurrent cancer in patient with EGFR mutation (ID 3134)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKI) responds to approximately 80% of the non-small cell lung cancer (NSCLC) patients with EGFR mutation. In other words, about 20% of the patients with EGFR mutations don’t respond. It was reported that resistance to EGFR-TKI is caused by secondary mutation at codon 790 (exon 20 mutation), Met amplification and hepatocyte growth factor (HGF)-MET signaling. The aim of this study is to explore the type of EGFR mutation, phosphorylated MET and HGF expression in tissues surgically removed for NSCLC with EGFR mutation impact on the sensitivity to gefitinib.

      Methods
      We studied 44 surgically resected NSCLC from 2001 to 2012. 43 cases were adenocarcinoma and 1 case was large cell neuroendocrine carcinoma. These surgical resections were taken from patients who were treated with gefitinib as first or second or third line therapy for postoperative recurrent cancer. The patients’ age ranged from 27 to 78years old (average 63.1 years old). There were 19 male and 25 female patients. There was 1 case of exon 18 point mutation, 23 cases of exon 19 deletion, 2 cases of exon 20 point mutation, 16 cases of exon 21 point mutation, and 2 cases of both exon 20 and 21 point mutation. We assessed non-responders progression within 2 months. Intermediate responders were considered as being effectively treated (at least stable disease) with gefitinib between 3 and 11 months. And long-term responders were considered to be effectively treated with gefitinib for over 12 months.

      Results
      Non-responders were 4 cases. Intermediate responders were 26 cases (including 11 cases of ongoing treatment). Long-term responders were 14 cases (including 1 case of ongoing treatment). Non-responders had two secondary mutation, one exon 19 deletion and exon 21 mutation. Intermediate responders had one exon 18 mutation, 14 exon 19 deletion, 10 exon 21 mutation and one both exon 20 and 21 mutation. long-term responder had eight exon 19 deletion, five exon 21 mutation and one both exon 20 and 21 mutation.

      Conclusion
      In our data, NSCLC with exon 20 mutaiton will respond to gefitinib if this NCCLC with another EGFR mutation. We will report the findings of non-responders excluding analyzed exon 20 mutation phosphorylated MET and HGF expression.

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    P2.21 - Poster Session 2 - Diagnosis and Staging (ID 170)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Prevention & Epidemiology
    • Presentations: 1
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      P2.21-003 - The relationship between the type of bone metastasis and EGFR gene mutation in non-small cell lung cancer (ID 2177)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The bone is the most common distant site of metastasis in non-small cell lung cancer (NSCLC), and patients with bone metastasis have a markedly poor prognosis. There are three types of bone metastasis; such as osteolytic type, osteoblastic type, and mixed type. Assessment of bone metastatic type may be important as a part of therapeutic strategy because it has been noted that osteoblastic tumors would have lead to both a better prognosis and activating epidermal growth factor receptor (EGFR) mutation presence. The aim of this study was to examine the relationship between the type of bone metastasis and clinical characteristics including EGFR gene mutation status in NSCLC patients.

      Methods
      We reviewed the records of 85 unresectable or postoperative recurrent NSCLC patients with at least one site of bone metastasis. The type of bone metastasis was classified by two radiologists reviewing the radiological examination as osteolytic type (OL), osteoblastic type (OB), and mixed-type from the CT findings.

      Results
      Median follow-up time for survivors was 25.4 months. There were 53 (62%) patients with unresectable NSCLC and 32 (38%) patients with postoperative recurrent disease. The number of patients with adenocarcinoma is 75 (87%). The bone metastasis type was OL group in 39 (46%) patients, OB group in 37 (43%) patients, and mixed type in 9 (11%) patients. Survival analysis incorporating mixed type bone metastasis into OB group revealed median survival time of 20.3 months and 30.9 months for OL and OB group, respectively. The difference was not significant (p=0.314), but OB group seems to have better prognosis than OL group. The prevalence of activating EGFR gene mutation was marginally significance in OB group (58%) than in OL group (36%) (p = 0.052). There are no significant relationship between the type of bone metastasis, and sex and smoking history.

      Conclusion
      This study shows that evaluating the type of bone metastasis by CT image enable prediction of EGFR gene mutation status and prognosis in NSCLC patients with bone metastases separately from sex, smoking habit, and race. The presence of osteoblastic metastases or the evolution to metastases should always be noted since it might represent an important predictive factor of response to EGFR-TKI treatment.

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    P3.03 - Poster Session 3 - Technology and Novel Development (ID 152)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.03-001 - The overxpression of TS protein induced by NPe6-PDT (ID 1339)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Malignant pleural mesothelioma(MPM) is a locally aggressive disease characterized by a poor prognosis and increasing. MPM tumors are usually related to asbestos exposure, and the incidence is anticipated to peak between 2020 and 2030 because of the lag time between asbestos expousere and the development of the malignancy. MPM is difficult to detect at an early stage, and surgical and radiotherapeutic approaches are ineffective when used independently, because MPM spreads diffusely in the surrounding chest wall. No universally accepted treatment approach currently exists.

      Methods
      We examined whether combination treatment consisting of pemetrexed chemotherapy and photodynamic therapy (PDT) using the photosensitizer, NPe6, enhanced the antitumor effect in vitro and in vivo models. We also investigated preclinical treatment schedules. Four human malignant mesothelioma cell line, (MSTO-211H, H2052, H2452and H28) were assayed using the WST assy after treatment with pemetrexed and NPe6-PDT. The treatment schedule for the combination treatment was examined using nude mice.

      Results
      In nude mice injected with MSTO-211H cells and then treared using a combination of pemetrexed and NPe6-PDT (10 mg/kg NPe6, 10 J/cm2 laser irradiation), the tumor volume decreased by 50% but subsequently increased, reaching the pretreatment value after 14 days. Pemetrexed treatment followed by NPe6-PDT resulted in an 80% reduction in the tumor size and inhibited re-growth. NPe6-PDT followed by pemetrexed treatment resulted in a 60% reduction in tumor size but did not inhibit re-growth.

      Conclusion
      Pemetrexed reportedly inhibits multiple enzymes in the folate metabolic pathway, with TS being the main target. In non-small cell lung cancer cell line, high baseline TS expression levels confer resistance to pemetrexed, and the TS level is correlated with pemetrexed efficacy in a variety of solid tumors. These results suggest that the overexpression of TS protein induced by NPe6-PDT may be associated with the failure of pemetrexed to exert a tumoricidal action. Therefore, we concluded that NPe6-PDT followed by pemetrexed did not enhance tumor cell lethality in the in vivo model. Combination treatment, consisting of pemetrexed followed by NPe6-PDT, should be further investigated as a new treatment modality for malignant pleural mesothelioma. In the future, this combination treatment may contribute to a reduction in local recurrence and a prolonged survival period in patients with malignant pleural mesothelioma.

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    P3.07 - Poster Session 3 - Surgery (ID 193)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P3.07-034 - Therapeutic outcomes in 24 cases of postoperative bronchopleural fistula in lung cancer surgery (ID 2737)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      Bronchopleural fistula (BPF) after lung resection is a life-threatening complication. Thoracic surgeons should always consider the risk of postoperative BPF and the management to avoid worst scenario, but it is still controversial of which is the best way to manage BPF. We herein describe the results of BPF and explore optimal treatment.

      Methods
      Data on 2270 patients with lung resection for NSCLC over a period from 2000 to 2012 were retrospectively reviewed. Details regarding surgery and subsequent treatment were carefully reviewed. Followed information was recorded; age, sex, clinical diagnosis, associated condition, TNM stage, time from primary operation to rethoracotomy, and postoperative outcome.

      Results
      The overall BPF incidence was 1.1% (24/2270). There were 20(83.3%) male and 4(16.7%) female, mean age was 67.1 years. BPFs occurred after pneumonectomy in 2(8.3%), lobectomy in 20 (83.3%) and sleeve resections in 2 (8.3%). In side right was in 20 (83.3%) and left was in 4 (16.7%). The histological types were 9 adenocarcinomas, 9 squamous cell carcinomas, 6 others. The pathological stage were stage IA in 6 cases, IB in 4, IIA in 3, IIB in 4, IIIA in 6 cases. Mean postoperative day was 19.8. In initial treatment, fenestration was 12 cases, primary closure using various techniques was 8 cases, and completion pneumonectomy was a case. Massive hemoptysis causing death owing to bronchial pulmonary artery fistula (BPAF) was in 3 cases. Primary closure using various techniques succeeded in 3 cases, while the repair failed in the other 5 case and 2 cases subsequently developed further fatal complications. The mortality rate of primary closure was 25% (2/8) and success rate was 38% (3/8). The mortality rate of fenestration was 8.3% (1/12), and success rate was 91.6% (11/12). The overall mortality rate for postoperative BPF was 25% (6/24); 3 cases were BPAF, 3 cases were aspiration pneumonia.

      Conclusion
      BPF remains a major complication in the surgery of lung cancer because of its high mortality and morbidity rate. Especially, the mortality rate of primary closure using various techniques was high, and aspiration pneumonia with consequent ARDS is fatal complication. To avoid death related to BPF, the surgeons should consider the fenestration as soon as the BPF was diagnosed.

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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.10-033 - Prognostic factors in stage III non-small cell lung cancer patients with postoperative brain metastases (ID 2084)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The brain is the most frequent site of distant metastases in patients with non-small cell lung cancer (NSCLC). In stages I-IIIA NSCLC, after complete resection of the primary tumor, brain metastases account for 9.4% to 36.8% of all recurrences. This study assessed the risk factors for brain metastasis and the prognostic factors for survival after brain recurrence in patients whose advanced NSCLC was resected.

      Methods
      A total of 101 patients with brain metastases occurring after resection of stage III NSCLC tumors at Tokyo Medical University Hospital between 1995 and 2010 were retrospectively reviewed.

      Results
      The median time to onset of brain metastasis was 11.2 months (1-72 months) and the median survival time from the diagnosis of brain metastasis was 18.5 months (1-60 months). Multivariate analysis revealed that the risk factors for brain metastasis in postoperative stage III NSCLC included the following parameters: adenocarcinoma,age <65 years at recurrence, N2-N3, incomplete resection, and vascular invasion. In addition, the significant favorable prognostic factors included the absence of neurologic signs and symptoms, single and small size of brain metastasis, age <65, and treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

      Conclusion
      It was possible to identify patientsat high-risk for brain metastases after surgery. For these patients, careful follow-up is needed after surgery. It is important to detect brain recurrence in patients with NSCLC before neurologic signs or symptoms develop, as early detection improves prognosis.

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    P3.19 - Poster Session 3 - Imaging (ID 181)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Imaging, Staging & Screening
    • Presentations: 2
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      P3.19-001 - Correlation between whole tumor size and solid component size on high-resolution computed tomography in the prediction of the degree of pathologic malignancy and the prognostic outcome in primary lung adenocarcinoma (ID 138)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      It is known that in lung adenocarcinoma, ground glass nodule (GGN) tumors have a better prognosis than solid tumors. The aim of this study is to determine whether it is more useful to evaluate the whole tumor size or only the solid component size to predict the pathologic malignancy and the prognostic outcome in lung adenocarcinoma.

      Methods
      Using high-resolution computed tomography (HRCT) data of 232 patients with adenocarcinoma 7 cm or less who underwent curative resection, we retrospectively measured the whole tumor and solid component sizes with lung window setting (WTLW and SCLW) and whole tumor sizes with a mediastinal window setting (WTMW).

      Results
      There was significant correlation between the WTLW and the measurements of pathological specimens (r=0.792, P<0.0001). The SCLW and WTMW values significantly correlated with the area of pathologically confirmed invasion (r=0.762, P<0.0001 and r=0.771, P<0.0001, respectively). The receiver operating characteristics area under the curve for WTLW, SCLW and WTMW used to identify lymph node metastasis or lymphatic or vascular invasion were 0.693, 0.817 and 0.824, respectively. Kaplan-Meier curves of DFS and OS were better divided according to SCLW and WTMW, compared with WTLW. Multivariate analysis of DFS and OS revealed that WTMW was an independent prognostic factor (HR=0.72, 95%CI=0.58-0.90, P=0.004 and HR=0.74, 95%CI=0.57-0.96, P=0.022, respectively).

      Conclusion
      The predictive values of the solid tumor size visualized on HRCT especially in the mediastinal window for pathologic high-grade malignancy and prognosis in lung adenocarcinoma less than 7 cm were greater than those of whole tumor size.

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      P3.19-020 - Multivariable analysis of the high resolution-CT findings of the presence or absence of epidermal growth factor receptor mutation for 476 primary lung adenocarcinomas (ID 1589)

      09:30 - 09:30  |  Author(s): N. Ikeda

      • Abstract

      Background
      The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor make very important role in chemotherapy for primary lung adenocarcinoma. It is necessary to examine EGFR mutation before medication, but it is difficult to examine for all patients. Our purpose is to determine EGFR mutation presence by HRCT findings of primary lung adenocarcinoma.

      Methods
      This study consists of 476 primary lung adenocarcinomas which were examined EGFR mutation (exon 18, 19 and 21) by a genetic analysis. EGFR mutation-positive group (EGFR-P) were 223 cases (resected =178, non-resected =45), and EGFR wild-type group (EGFR-W) were 253 cases (resected =161, non-resected =92). At first, presence of findings, such as much pleural effusion, atelectasis, or secondary pneumonia, that come to have difficulty in evaluation of size and the character of tumor, was determined. Then, all evaluable parameters were analyzed. The high resolution-CT (HRCT) findings that were analyzed independently by 2 radiologists with special attention were 21 parameters (tumor size, well-defined margin, irregular margin, spiculation, lobulation, pure ground-glass opacity (GGO), part-solid, solid, air bronchogram, cavity, calcification, broncho-vascular convergence, pleural indentation, pleural concave, pleural thickness, lymphangitis carcinomatosis, emphysema, interstitial pneumonia, pulmonary metastasis, pleural effusion, and lymph node enlargement). The age, gender and smoking history were additionally reviewed. These parameters were evaluated with Chi square test and multivariate analysis. A p-value less than 0.01 were considered to indicate a statistically significant difference.

      Results
      The cases that were hard to analyze a tumor into by such as atelectasis were two (EGFR-P) and 26 (EGFR-W), respectively. A statistical significant difference was present (p=3.4E-05). Chi square test showed a statistically significant difference about "part-solid (p=5.5E-06)", "air bronchogram (p=0.0036)" and "pleural indentation (p=0.0002)" more frequently in EGFR-P than in EGFR-W. Similarly “woman (p=1.3E-09)” and “non-smoker (p=2.7E-13)” were observed more frequently in EGFR-P than in EGFR-W. On the other hand, “solid (p=2.1E-07)”, “cavity (p=0.0004)”, “emphysema (p=5.1E-14)”, “interstitial pneumonia (p=3.1E-8)” and “lymph node enlargement (p=0.0008)” were observed more frequently in EGFR-W than in EGFR-P. And Multivariable analysis showed that “cavity (p=0.003)”, “emphysema (p=0.001)” and “interstitial pneumonia (p=0.001)” were observed more frequently in EGFR-W than in EGFR-P. On the other hand, there was no parameter that became statistically significantly more frequently in EGFR-P than EGFR-W. By the multivariable analysis, there was no significant statistical difference about gender and smoking history.

      Conclusion
      The cases that were hard to analyze a tumor into by such as atelectasis were significant in EGFR-W. Some HRCT findings (part-solid, solid, air bronchogram, cavity, pleural indentation, emphysema and interstitial pneumonia) indicated more statistically significant usefulness for a diagnosis of the EGFR mutation. Especially multivariable analysis showed that HRCT findings (cavity, emphysema and interstitial pneumonia) were more statistically significant about EGFR mutation than gender and smoking history.