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D. Boffa
Moderator of
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MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 12
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
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MINI32.01 - Computed Tomography Lymphography by Transbronchial Injection of Iopamidol for Preoperative Non-Small Cell Lung Cancer Patients (ID 3009)
18:30 - 18:35 | Author(s): H. Takizawa, K. Kondo, M. Tsuboi, K. Kajiura, T. Otani, H. Toba, Y. Kawakami, S. Sakiyama, A. Tangoku
- Abstract
- Presentation
Background:
Sentinel node (SN) is defined as the first node draining a tumor, and should be the first site affected in lymphatic dissemination. Recently, with the increased incidence of small sized non-small cell lung cancer (NSCLC), segmentectomy is again under evaluation for clinical T1a N0 NSCLC patients. In the ongoing trial regarding segmentectomy (JCOG0802), the eligibility criteria for segmentectomy include a prerequisite of no lymph node metastasis by intraoperative findings because node-positive cases have a chance to be locoregionaly controlled and to be correctly staged by converting to lobectomy. Therefore, intraoperative sampling and frozen sectioning of true SNs is important in ensuring the radicality of segmentectomy. The objective of this study was to assess the safety and the feasibility of computed tomography (CT) lymphography by transbronchial injection of a water-soluble extracellular CT contrast agent which was developed as a new method for identifying SNs in patient with NSCLC.
Methods:
Between April, 2010 and January, 2015, clinical stage I NSCLC patients who were candidates for lobectomy or segmentectomy were enrolled in this study. An ultrathin bronchoscope was inserted to the target bronchus under the guidance of virtual bronchoscopic navigation images. CT images of the chest were obtained 30 seconds after 2 or 3ml of iopamidol was injected through a microcatheter. SNs were identified when the maximum CT attenuation value of the lymph nodes in postcontrast CT images increased by 30 Hounsfield units or more compared to precontrast images. Patients underwent video-assisted thoracic surgery lobectomy with standard lymph node dissection. SNs were harvested according to findings of CTLG and to intraoperative findings of near-infrared fluorescence imaging with indocyanine green. All lymph nodes, including SNs, were histopathologically examined by standard hematoxylin and eosin staining.
Results:
The ultrathin bronchoscope could access targeted bronchus, and iopamidol was delivered into the peritumoral area in all 41 patients without any complications. SNs were identified in 38 of 41 patients (92.7%), and the average number of SNs was 1.4 (range: 1-4). Lymph node metastases were found in 6 cases, including one false-negative case. Enlargement of lymphatic vessel was seen in 3 out of 6 (50%) cases with lymph node metastases, whereas it was seen in 6 out of 35 cases (17%) without lymph node metastases.
Conclusion:
CT lymphography by transbronchial injection of iopamidol was a safe and feasible method to identify SNs in clinical stage I NSCLC patients. Lymphatic remodeling including peritumoral lymphangiogenesis and enlargement of lymphatic vessel has been reported to one of the crucial step of lymph node metastasis of cancer. Enlargement of lymphatic vessel seen in CT lymphography may be a risk factor for lymph node metastasis of NSCLC.
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- Abstract
- Presentation
Background:
Lung cancer has been the leading cause of cancer related mortality for the past decades worldwide and in China. Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases. For patients with early stage NSCLC, surgical resection is the mainstay of the treatment. This study aimed to better understand characteristics of NSCLC patients who underwent curative-intent lung surgical resections in China.
Methods:
Data were obtained from the NSCLC surgical outcome registry, which included 3,464 NSCLC patients who underwent curative-intent surgical resections from 13 tertiary hospitals in 11 provinces in 2013 and 2014. The registry documented detailed information on demographics as well as perioperative parameters.
Results:
The median age at the time of surgery was 60 (range 14 to 92) years, and 64.0% of the patients were male. Approximately 49.1% had a smoking history and 12.6% had a family history of cancer. About 45.7% patients had at least one comorbidity. The most prevalent comorbidities were cardiovascular disease, metabolic disease, respiratory disease, and other tumor, which affected 45.2%, 15.5%, 13.3% and 9.7% of the patients, respectively. The pulmonary function test showed a mean FEV1 of 2.33 (SD=0.63, range 0.32 to 4.81) L and FEV1/FVC of 79.3% (SD=12.6%, range 0.5% to 100.0%). The types of resection were lobectomies (lobectomies, bi-lobectomies and sleeve lobectomies) 79.3%, sublobar resections (segmentectomies and wedge resection) 8.5%, pneumonectomies 7.0%, and others 4.3%. 44.5% resections were performed by video-assisted thoracoscopic surgery (VATS). Adenocarcinoma and squamous cell carcinoma were the most common types of NSCLC, accounting for 60.2% and 31.4% of the patients, respectively. The most common tumor locations were right upper lobe (26.9%), left upper lobe (22.8%), right lower lobe (19.4%), left lower lobe (16.5%), and right middle lobe (6.5%). Pathologic staging showed 48.5% patients had stage I tumor; stage II, III, and IV accounted for 23.0%, 25.3% and 3.3%.
Conclusion:
The NSCLC patients who underwent curative-intent lung resection surgeries in China were relatively young and had good lung function. Adenocarcinoma and squamous cell carcinoma were the most common types. Nearly half of the procedures were performed by VATS and almost one out of two patients had pathologic stage I disease.
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MINI32.03 - Accuracy of Respiratory Dynamic Computed Tomography for the Detection of Pleural Adhesions (ID 805)
18:40 - 18:45 | Author(s): J. Tokuno, T. Shoji, R. Sumitomo, K. Yamanashi, C. Huang
- Abstract
- Presentation
Background:
Video-assisted thoracic surgery (VATS) plays an important role in thoracic surgery especially for early stage lung cancer because it is less invasive. However, the existence of severe pleural adhesions may make VATS difficult and complicated. So, preoperative detection of pleural adhesions can be very useful for the assessment of surgical approach. The aim of this study was to assess the accuracy of inspiration and expiration computed tomography (respiratory dynamic CT: RD-CT) in evaluation of pleural adhesions prior to thoracic surgery. Video-assisted thoracic surgery (VATS) plays an important role in thoracic surgery especially for early stage lung cancer because it is less invasive. However, the existence of severe pleural adhesions may make VATS difficult and complicated. So, preoperative detection of pleural adhesions can be very useful for the assessment of surgical approach. The aim of this study was to assess the accuracy of inspiration and expiration computed tomography (respiratory dynamic CT: RD-CT) in evaluation of pleural adhesions prior to thoracic surgery.
Methods:
From January to December 2014, RD-CT was performed on 107 patients undergoing thoracotomies (both VATS and open surgery, except for pneumothorax). We assessed synchronous motion during respiration on RD-CT using a three-dimensional CT image software, as Sliding Score. Regarding intraoperative findings, we categorized the severity of pleural adhesions into 4 groups as Adhesion Grade. Then, comparing Sliding Score and Adhesion Grade, we assessed the utility of preoperative evaluation. In addition, to confirm these patients could expire enough in expiration phase, we assumed lung volume in expiration phase/ inspiration phase as CT- Respiratory Ratio in each case.
Results:
Operations were performed mainly for lung cancer (78 cases; 72.9%), others are metastatic lung tumor, mediastinal tumor, lung abcess and so on. A negative correlation between Sliding Score and Adhesion Grade was revealed. Sliding Score in adhesion positive patients was significantly higher than that in adhesion negative patients (P < 0.0001). The sensitivity of RD-CT was 63.6%, specificity was 74.1%, and accuracy was 72%. Among 62 patients with a CT-Respiration Ratio of less than 0.65, the sensitivity of RD-CT was 77.8%, specificity was 86.8%, and accuracy was 85.5%. Regarding severe adhesions, RD-CT demonstrated a sensitivity of 100% in all 107 patients. No significant correlation was revealed between CT- Respiratory Ratio and respiratory function or Adhesion Grade.
Conclusion:
RD-CT may be useful for detecting the presence of pleural adhesions, especially to rule out the severest adhesions. It can be adopted as one of the criteria for deciding the surgical approach, VATS or open surgery. And it may enable an operation to be performed more safely and systematically.
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MINI32.04 - Clinico-Pathological Correlations and the Role of Brain MRI in Combined Clinical Staging for Resectable Lung Cancer (ID 2441)
18:45 - 18:50 | Author(s): J. Vernon, N. Andruszkiewicz, L. Schneider, C. Schieman, C.J. Finley, Y. Shargall, C. Fahim, F. Farrokhyar, W.C. Hanna
- Abstract
Background:
In our model of Combined Clinical Staging (CCS) for lung cancer, patients with a Computerized Tomography (CT) scan of the chest that does not show distant metastases will then routinely undergo whole body Positron Emission Tomography (PET/CT) and Magnetic Resonance Imaging (MRI) of the brain prior to any therapeutic decision. We aim to determine the accuracy of CCS and the value of brain MRI in this population.
Methods:
A prospective database was queried for all patients who underwent resection of lung cancer from 01/2012 to 06/2014. Demographics, wait times, clinical and pathological stage (7[th] edition AJCC/UICC), and costs of staging were collected. Krippendorff’s alpha was used to determine correlation between clinical and pathological stage.
Results:
Of 315 patients with primary lung cancer, 55.6% were female and the median age was 70 (27-87, Table 1). The mean time from initial CT scan to surgical treatment was 9.12 +/- 6.0 weeks. Krippendorff’s alpha between CCS and pathological stage was 0.193 (0.125 to 0.260, Table 2). When correlation was analyzed without consideration for sub-stages A and B, 49.8% (157/315) of patients were staged accurately, 39.7% (125/315) were over-staged, and 10.5% (33/315) were under-staged. Only 4.7% (15/315) of patients underwent surgery without appropriate neo-adjuvant systemic treatment. Preoperative brain MRI detected asymptomatic metastases in 4/315 patients (1.3%). At a median postoperative follow-up of 16 months (1-40), 7 additional patients developed symptomatic brain metastases, all of which had normal brain MRI preoperatively. The total cost of CCS was $416,924 over the study period, with $131,824 (31.6%) going towards brain MRI.Table 1: Baseline descriptive data, N=315
Age Mean (SD) 69.80 (9.62) (Min: 27.34, Max: 86.61) Gender Female (%) 175 (55.6%) Male (%) 140 (44.4%) Weeks First Visit to Consent Mean (SD) 5.49 (8.15) (Min: 0, Max: 63) Weeks Consent to Surgery Mean (SD) 2.24 (2.07) (Min: 0, Max: 11) Weeks Initial CT to Surgery Mean (SD) 9.12 (6.01) (Min: 0, Max: 53) Weeks First Visit to Surgery Mean (SD) 8.00 (8.25) (Min: 0, Max: 64) Brain Metastases at Baseline (%) 4 (1.3%) Brain Metastases at Follow Up (%) 11 (3.5%) Table 2: Frequency and agreement of CCS and pathological stage
Stage (N=315) Clinical Stage N (%) Pathological Stage N (%) Same Staging by Both (True Positives) 0 1 (0.3%) - - Stage IA 89 (28.3%) 103 (32.7%) 55 Stage IB 39 (12.4%) 82 (26.0) 19 Stage IIA 42 (13.3%) 47 (14.9%) 7 Stage IIB 32 (10.2%) 42 (13.3%) 12 Stage IIIA 78 (24.8%) 39 (12.4%) 16 Stage IIIB 21 (6.7%) 0 (0.0%) 0 Stage IV 13 (4.1%) 2 (0.6%) 2 Krippendorff's Alpha for level of agreement = 0.193 (0.125 to .260)
Conclusion:
CCS is effective for patients with resectable lung cancer, with less than 5% of patients being under-staged in a way that denied them appropriate systemic treatment before surgery. Brain MRI is a low yield and high cost intervention in this population, and its routine use should be questioned.
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MINI32.06 - Clinical Impacts of Tumor Hypoxia Imaging with FAZA and ATSM PET in NSCLC (ID 182)
19:00 - 19:05 | Author(s): T. Kinoshita, H. Fujii, M. Anraku, Y. Hayashi, H. Asamura
- Abstract
- Presentation
Background:
The noninvasive dynamic characterization of hypoxia using molecular imaging approaches is supportive for evaluation of malignant tumor. In this study, we evaluated the clinicopathological impact of newly developed tumor hypoxia PET tests for localized non-small cell lung cancer (NSCLC).
Methods:
Forty-nine patients with localized NSCLC were enrolled[F1] [木下智成2] . They underwent chest hypoxia PET tests, namely [18]F-fluoroazomycin arabinoside (FAZA) and/or [62]Cu-diacetyl-bis (N4)-methylsemithiocarbazone (ATSM) PET in addition to routine whole-body [18]F-fluorodeoxyglucose (FDG) PET before treatment. Uptake of hypoxic tracers was quantified by calculating maximum standard uptake values (SUVmax) and tumor muscle ratios (TMR).
Results:
The uptake of [18]F-FAZA were in positive proportion to that of [62]Cu-ATSM (P < 0.05). Neutrophil lymphocyte ratio and tumor size were significantly correlated with uptake both in [18]F-FAZA (P < 0.01) and [62]Cu-ATSM (P < 0.05 in [18]F-FAZA and [62]Cu-ATSM). Pathologically, the case with vascular or pleural invasion, which indicate tumor malignancy, had higher uptake of [18]F-FAZA (P < 0.05). Those accumulations increased according to advanced TNM staging (P < 0.05). The patient with higher uptake of these tracers significantly had a poorer overall survival (P < 0.01 in [18]F-FAZA and P < 0.05 in [62]Cu-ATSM), and progression-free survival (P < 0.01 in [18]F-FAZA and P < 0.05 in [62]Cu-ATSM).
Conclusion:
[18]F-FAZA and [62]Cu-ATSM can provide useful information on tumor malignancy and prognosis, and might contribute toward guiding individualization of treatment of localized NSCLC. Figure 1Figure 2
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MINI32.07 - A Phase I Feasibility Study of Kilovoltage Intrafraction Monitoring for Lung Cancer (ID 1036)
19:05 - 19:10 | Author(s): F. Hegi-Johnson, J. Barber, K. West, V. Gebski, S. Cross, S. White, R. Yegiaian-Alvandi, P. Keall
- Abstract
- Presentation
Background:
New technologies in radiotherapy of lung tumours aim to reduce toxicity and increase tumour control by increasing the dose delivered, and reducing the size of radiotherapy margins. Kilovoltage intrafraction monitoring (KIM) is a novel image guidance technology, which permits visualisation of fiducials implanted into the tumour whilst the radiotherapy beam is on. KIM has been used in both prostate[1] and liver tumours[2], and has been shown to increase the accuracy of radiotherapy delivery. In this Phase I study we aim to establish whether it is feasible to use KIM to monitor the motion of lung tumours during radiotherapy delivery. 1. Ng J et al. IJROBP 2012:84(5):e656 2.Poulsen P et al. Radiotherapy and Oncology 2014:111(3):424
Methods:
Patients receiving curative radiotherapy for lung cancer will have between 3-5 fiducials inserted into their tumour during endobronchial ultrasound (EBUS). Radiotherapy will be planned and delivered as per standard departmental protocols for lung cancer patients. 4D-cone beam CT (CBCT) will be performed , in conjunction with acquisition of KIM images and respiratory motion signal acquisition on the 1[st], 6[th], 11[th], 16[th], 21[st], 26[th], and 30[th] fractions before treatment to assess the accuracy of patient and tumour position.
Results:
Initial studies in a respiratory motion phantom have indicated that 0.4mm diameter Gold Anchor fiducials are visible during radiotherapy treatment. Ethical approval has been obtained with patient recruitment to the study to commence shortly. The primary endpoint of this study is the successful visualisation by the KIM technique of fiducials inserted into the tumour. Each patient will have a minimum of 3 fiducials (markers) inserted. As the implanted fiducials may be migrated or lost, the definition of technical success will vary according to the number of fiducials present. In the case of 1 to 3 markers being present, segmentation of at least 1 marker will be required for the image acquisition to be deemed successful. In the case of 4 or more fiducials being present, segmentation by the KIM technique of at least 2 markers for each image will be required for the image acquisition to be deemed successful. Secondary endpoints include assessment of the stability of implanted markers, and the rate of marker migration, quantitative assessment of tumour motion, assessing the impact of tumour motion on dosimetry and an assessment of toxicity associated with marker insertion.
Conclusion:
Lung tumours move during radiotherapy treatment, both between radiotherapy fractions and whilst the radiotherapy dose is being delivered[3]. Establishing the feasibility of KIM will enable the visualization of tumour motion whilst the radiotherapy treatment is being delivered. This is currently impossible on a standard linac, limiting the ability of the clinician to implement changes in margin size, which could potentially reduce the severity of side-effects for patients. Assessing intra-fraction motion of lung tumours is a key step in this process – by identifying the uncertainty in treatment, we will in the future be able to implement gating and tracking of tumours, thus resulting in safer and more effective treatment. 3. Sonke J. et al. IJROBP 2008:70(2):590
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MINI32.08 - Identification of a Meta-Gene Network Associated with Metformin Sensitivity and Recurrence in Stage I Non-Small Cell Lung Cancer (ID 1727)
19:10 - 19:15 | Author(s): C.A. Frankenberger, C.W. Seder, N. Lund, R.A. Medairos, M.J. Liptay, P. Bonomi, J.A. Borgia
- Abstract
- Presentation
Background:
We recently reported an association between progression-free survival and metformin exposure in patients with early stage non-small cell lung cancer (NSCLC). Local recurrence in stage I disease is estimated to be as high as 50% in US populations. Therefore, a method to identify NSCLC patients who are most likely to benefit from metformin treatment has potential clinical relevance.
Methods:
Three previously published, publically available gene expression array data sets documenting the effects of metformin treatment on transcriptional activity in human cell lines were used for the initial stages of the present study. These data sets were evaluated individually for enrichment of differentially expressed genes with a gene set analysis related to biological processes also performed. Differentially expressed genes common to all three studies were then used to form a metformin meta-gene. This combined meta-gene was evaluated topologically using a protein-protein interaction database to determine if any gene products had previously observed direct interactions. The metformin meta-gene network was then examined in expression array data sets from stage I NSCLC patients (n=293) assembled from multiple published studies.
Results:
We identified several biological themes resulting from metformin treatment, including: immune cell differentiation, response to hypoxia, steroid receptor signaling, alternate splicing, and changes in cellular metabolism. Intersecting the differentially expressed genes from each data set, we identified 105 genes consistently up-regulated and 30 genes consistently down-regulated by metformin treatment, forming a tissue-independent meta-gene for metformin effects. Two networks of interacting genes were identified in this analysis; the first network consisting of 27 genes (22 up-regulated and 5 down-regulated) and the second consisting of three up-regulated genes.This meta-gene was then examined in two independent cohorts of stage I adenocarcinoma. In the first cohort (n=125), patients clustered into two groups when k-means analysis was performed with respect to the 30 genes in the metformin meta-gene network. These patients had a significantly (p=0.014) different incidence of recurrence between the two clusters. This result was independently validated in the second data set (n=168) where patients clustered into two groups and also demonstrated significant stratification of recurrence (HR=1.21; p=0.001).
Conclusion:
We have identified a meta-gene of interacting proteins associated with both metformin therapy and recurrence-free survival in early stage lung cancer patients. This suggests a potential method for identifying NSCLC patients most likely to benefit from metformin therapy, and furthermore, identifies mechanistic avenues by which metformin treatment may benefit early stage lung cancer patients.
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MINI32.09 - The Combination of Serum Biomarkers CYFRA 21-1 and CEA in the Prognostication of Early Stage Non-Small Cell Lung Cancer (NSCLC) (ID 1353)
19:15 - 19:20 | Author(s): T. Muley, Y. He, V. Rolny, J. Riedlinger, B. Wehnl, F. Dayyani, M.A. Schneider, C. Stolp, H. Dienemann, M. Meister, F. Herth
- Abstract
Background:
Serum based biomarkers are routinely used for prognosis and monitoring of some solid tumors (e.g. colorectal, pancreatic, and ovarian carcinomas) but have not yet been widely adopted in NSCLC management. We prospectively evaluated the prognostic role of serum biomarkers in the management of early stage NSCLC treated at a single specialized center.
Methods:
Prospective collection of blood samples from patients (pts) with resectable NSCLC was done before surgery and thereafter during routine follow up visits. A panel of serum biomarkers was measured, including CYFRA 21-1 (Cytokeratin fragment 19) and CEA (carcinoembryonic antigen). Several risk models were established and prediction accuracy was assessed by C-Index (generalized AUC), Hazard Ratio (HR) at median split and Net Reclassification Index (NRI).
Results:
275 pts were enrolled (n= 180 men). Histology was adenocarcinoma (AC) in 133 pts (48.4%), squamous cell carcinoma in 103 pts (37.5%), and other in 39 (14.1%). Stages were based on IASLC 6[th] edition and included IA (n= 39), IB (n= 120), IIA (n= 7), IIB (n= 66), and IIIA (n= 43). 92 pts (33.5%) recurred after a median of 11.9 months follow-up. Occurrence of first relapse showed two main peaks, at 6-12 months and 21-27 months, respectively, indicating a high-risk group for early relapse. In multivariate analyses, clinical prognostic factors included: TNM stage, age, gender, histology, and smoking history. Addition of the baseline CYFRA 21-1 and CEA biomarkers significantly increased the number of pts allocated to the correct prognostic group in the model by 13.2% compared to clinical variables only (HR for first relapse from 2.14 to 3.02; NRI 0.132).
Conclusion:
In this largest cohort of NSCLC pts with prospective serum biomarker sample collection to date, time to first relapse in localized NSCLC showed subgroups of early and late relapse pts. Baseline levels of the CYFRA 21-1 and CEA biomarkers identified a higher number of pts who were likely to recur within the first year and might benefit from closer surveillance. The CYFRA 21-1 assay is currently not cleared or approved for use in the USA.
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MINI32.11 - 10 Years of National Lung Cancer Audit in the UK (ID 428)
19:30 - 19:35 | Author(s): M.D. Peake, P. Beckett, I. Woolhouse
- Abstract
- Presentation
Background:
The UK National Lung Cancer Audit has been collecting, analysing and reporting data on the management of lung cancer patients for 10 years. This abstract summarises the progress made in this period.
Methods:
Hospitals working within the UK National Health Service are invited to submit data to a web portal on all incident cases of lung cancer (and mesothelioma). The dataset covers demographics, referral, investigation, diagnosis, treatment and outcome.
Results:
Clinical and organisational engagement in the audit increased rapidly over the first 5 years such that currently all hospitals submit data on 100% of the expected incident cases, with 93% of cases having stage and performance status recorded. Measures of good practice have shown incremental improvements (e.g. histological confimation rate 68% to 75%, proportion with subtyped NSCLC 64% to 87%, proportion of patients seen by a specilaist nurse 51% to 84%, proportion receiving anti-cancer treatment 45% to 60%. The surgical resection rate in histologically-confirmed NSCLC has risen from 14% to 23% in keeping with other data sources, reinforcing the suggestion that these improvements reflect real changes in practice rather than just better data. Survival has improved in patients with early stage disease and good PS as previously published utilising the audit data (Khakwani et al 2013). Moreover, overall survival in the whole cohort appears to be improving when clinical features (age, sex, stage PS) are taken into acocunt as shown in Table 1.*Adjusted for age, sex, stage and PS
Despite these overall improvements in process and outcome, there remains a variatin in ractice across organisations that perists after adjustment for case-mix (example Figure 1). Figure 1Year HR* CI 2008 1.0 - 2009 0.97 0.96-0.99 2010 0.96 0.94-0.98 2011 0.90 0.90-0.93 2012 0.88 0.87-0.90 2013 0.87 0.85-0.89
Conclusion:
The NLCA has been instrumental in driving improvements in lung cancer care in the UK. Future comparative audit projects spanning national and international boundaries hold the promise of further insights into variations in care and improvement in outcomes for our patients.
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- Abstract
- Presentation
Background:
Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitors (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to IIIA EGFR-mutated NSCLC.
Methods:
Patients with surgically resected stage IB (with high risk factors) to IIIA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other received platinum-based chemotherapy supplemented by a consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease free survival (DFS).
Results:
39 patients were enrolled between February 2011 and December 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 18 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). In the Cox proportional hazards model, the treatment groups and pTNM stage showed a statistically significant, the HR was 0.136 (95%CI: 0.022-0.829, p = 0.030) and 5.498 (95%CI: 1.333-22.673, p = 0.018) respectively. Adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.Figure 1
Conclusion:
The results suggest that, firstly, chemotherapy plus orally icotinib displayed a longer DFS compared with chemotherapy only, and secondly, patients receiving extra orally icotinib showed favorable tolerance without severe side effects. Nonetheless, our results are promising and future trials with larger sample sizes could confirm our current data.
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MINI32.13 - Racial/Ethnic and Gender Differences in Treatment and Survival of Early-Stage Non-Small Cell Lung Cancer in an Integrated Health Care System (ID 1083)
19:40 - 19:45 | Author(s): L.C. Sakoda, K.M. Uppal, K.B. Albers, M. Oehrli, L.A. Habel, C.P. Quesenberry Jr.
- Abstract
Background:
In the U.S., racial/ethnic and gender differences in treatment and survival of early stage non-small cell lung cancer (NSCLC) have been reported. These findings come largely from analyses of SEER-Medicare data, which inherently exclude younger and managed care patients, up through 2005. Whether such differences exist in an integrated health care system, other than the U.S. Military Health System and Veterans Health Administration, has not been comprehensively examined.
Methods:
Using electronic health record and cancer registry data from Kaiser Permanente Northern California, a fully integrated health care system, we identified a cohort of 1,566 patients of non-Hispanic White, Asian/Pacific Islander, Black, or Hispanic race/ethnicity diagnosed with incident stage I/II NSCLC at ages 21 to 80 years from 2004 to 2011. Patients were followed from NSCLC diagnosis to health plan termination, death, or study end (through 2013), whichever occurred earliest. We examined whether the following prognostic factors (at NSCLC diagnosis, unless otherwise specified), in addition to 3-year overall survival, differed statistically (p<0.05) by race/ethnicity or gender: age; marital status; smoking history; comorbidity score; tumor stage, size, and histology; and receipt, modality, and timing of initial treatment. Using multivariable Cox regression, we further examined the extent to which race/ethnicity and gender were associated with overall survival after accounting for other prognostic factors.
Results:
Our cohort included 1137 non-Hispanic Whites (482 men, 655 women); 232 Asian/Pacific Islanders (95 men, 127 women); 126 Blacks (52 men, 74 women); and 71 Hispanics (36 men, 35 women). The median age at diagnosis was 68 years. Overall, 92% were treated (89% of those treated by surgery), within 1.8 months post-diagnosis on average, and 41% died during 69,894 person-years of follow-up (median=3.3 years). Comparing across the race/ethnicity groups, non-Hispanic Whites were generally older at diagnosis, while Asian/Pacific Islanders were more likely to be married, never or former smokers, have a lower comorbidity score, and diagnosed with adenocarcinoma. The group most commonly treated with surgery was Asians/Pacific Islanders (87.5%), followed by Hispanics (81.7%), non-Hispanic Whites (79.9%), and Blacks (65.1%), with 3-year overall survival probabilities of 77%, 73%, 69%, and 63%, respectively. Compared to women, men were more likely to be married, former or current smokers, have a higher comorbidity score, and have a tumor of higher stage, greater size, and squamous cell histology, although both their receipt of surgery (women: 82%, men: 78%) and 3-year overall survival probabilities (women: 71%, men: 69%) were similar. After accounting for age, marital status, smoking history, comorbidity score, tumor characteristics, and receipt, modality, and timing of initial treatment, overall survival was similar for Asian/Pacific Islanders (hazard ratio (HR): 0.90; 95% confidence interval (CI): 0.69-1.17), Hispanics (HR: 0.96; 95% CI: 0.66-1.42), and Blacks (HR: 0.99; 95% CI: 0.75-1.31) compared to non-Hispanic Whites, and for men (HR: 0.95; 95% CI: 0.80-1.13) compared to women.
Conclusion:
Among early stage NSCLC patients in our integrated health care system, we found racial/ethnic differences in treatment, but no racial/ethnic or gender differences in overall survival after accounting for treatment and other prognostic factors.
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MINI32.14 - Primary Early-Stage Lung Cancer Following Head and Neck Cancer: A Population Based Study of Treatment and Survival in the Netherlands (ID 1433)
19:45 - 19:50 | Author(s): A.V. Louie, R. Damhuis, C. Haasbeek, A. Warner, D. Rodin, B. Slotman, C.R. Leemans, S. Senan
- Abstract
- Presentation
Background:
Second primary lung cancer (SPLC) is an important cause of death in survivors of head and neck squamous cell cancer (HNSCC). The goal of this Dutch population study was to compare treatment patterns and outcomes in early-stage SPLC after HNSCC.
Methods:
Details on all patients in a population of 16 million diagnosed with lung cancer between 1997 and 2011 were obtained from the Netherlands Cancer Registry. After excluding patients with a history of other malignancies, patients were dichotomized with a primary lung cancer or a SPLC after HNSCC. The latter included oral cavity, oropharynx, larynx, and hypopharynx sub-sites. Baseline characteristics of early-stage primary and SPLC were compared using the chi-square, fisher’s exact, or t-test, where appropriate. After stratifying patients into five consecutive 3-year time periods, the Chi-Square Trend test was used to determine trends in treatment patterns over time. Overall survival was calculated using the Kaplan-Meier method, and the log-rank test used to assess differences in survival. 30- and 90-day treatment related mortality were calculated. To assess for stage migration due to routine availability of PET-staging, as well as the availability of stereotactic ablative radiotherapy (SABR), outcomes were analyzed before and after 2005. All statistical tests were two-sided and considered significant when p<0.05.
Results:
Of the 153,330 lung cancer patients, 19,501 with a history of a non-HNSCC primary cancer were excluded from the analysis. Of the 133,829 remaining patients, 2,556 (2%) represented a SPLC following HNSCC. SPLC patients were more likely to present in stage I (27% versus 16%, p<0.01) rather than stage IV (34% versus 44%, p<0.01). For early-stage SPLC, initial HNSCC anatomical subsites were most commonly larynx (53%) and oral cavity (24%). Treatment for early-stage SPLC included surgery (53%), radiotherapy (RT, 33%), or best supportive care (14%). The proportion of RT patients undergoing SABR was unknown. When compared to surgery, early-stage SPLC patients receiving any-form of RT tended to be older, with more advanced T-stage disease, poorly differentiated histology, and lower rates of pathologic diagnosis (all p<0.01). The proportion of all early-stage lung cancer patients receiving surgery over time remained stable in the primary setting (range: 59-63%, p=0.69), but decreased for early-stage SPLC patients (range: 68-42%, p<0.01). The use of RT increased over time for both primary (range: 21-30%, p<0.01) and early-stage SPLC patients (range: 23-43%, p<0.01). 30- and 90-day treatment related mortality rates were higher in surgical versus RT patients in both pre-2005 (3.8%, 8.6% versus 4.0%, 8.0%) and post-2005 (2.3%, 4.0% versus and 0%, 3.2%) eras. Overall, early-stage SPLC surgical patients had improved survival when compared to RT patients (p<0.01). In the post 2005 era, however, survival was similar for these two modalities (p=0.13).
Conclusion:
In survivors of HNSCC who develop early-stage SPLC, RT deserves attention as an alternative gold standard to surgery. Previous studies indicated that a majority of RT delivered for early-stage NSCLC after 2006 was SABR [Palma D, 2010]. Despite negative selection of poorer baseline characteristics, use of RT resulted in comparable survival and lower post-treatment mortality when compared to surgery in the modern era.
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Author of
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GR 01 - Management of Challenging Clinical Scenarios in Localized Lung Cancer (ID 14)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:G. Darling, J. Mitchell
- Coordinates: 9/08/2015, 14:15 - 15:45, 601+603
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GR01.03 - T4 Lung Tumors According to the New Classification - What Is the Role of Surgery? (ID 1830)
15:00 - 15:20 | Author(s): D. Boffa
- Abstract
- Presentation
Abstract:
Surgical resection offers the best chance of cure for most patients with localized non-small lung cancer (NSCLC). However, the risk-benefit deliberation for surgery becomes less clear in patients with more locally advanced tumors (T4), because the procedures are typically more dangerous (higher risk) and the patient’s prognosis is worse (benefit less clear). That being said, surgery remains a curative option for a significant proportion of patients with T4 tumors. In order to minimize risk and maximize benefit, surgeons should select patients with 1) T4 tumors that can be removed safely, 2) T4 tumors that can be completely removed (R0) and 3) patients that are less likely to experience early systemic failure. The group of T4 NSCLC tumors that have historically been amenable to safe surgical resection include those that invade the spine, trachea, esophagus great vessels, and atrium. The 7[th] edition of the lung cancer stage classification system expanded the T4 designation to include tumors that involve a nodule in a separate ipsilateral pulmonary lobe. The recently released proposal for the 8[th] edition of the lung cancer stage classification system has moved tumors greater than 7cm in maximum diameter and tumors that invade the diaphragm to the T4 category. We have previously stated that changes in staging nomenclature should NOT be taken as justification for changing the way a patient is treated (because the revision only considers prognosis without any regard to treatment). However, these additional members of the T4 staging group pose the same risk-benefit conundrum that the others members pose and are discussed. Global health should be assessed as this is a critical component to the surgical risk calculation for patients. This typically includes an assessment of comorbid condition severity, pulmonary function testing, exercise testing and cardiopulmonary stress testing in patients at risk for cardiac disease. Strategies for safe removal of T4 tumors typically center around preparation for the unexpected. The supporting services should be alerted to not only the planned elements of the case but also possible needs in the event of a more extensive resection. The anesthesia team should be prepared to deal with abrupt bleeding (e.g. appropriate intravenous access that is located away from vessels that are likely to be clamped), the need for alternate ventilation strategies (e.g. jet ventilation). Any surgical specialty that could support an extended resection (e.g. spine service) should be alerted to the possibility. Surgeons should adjust their surgical approach to not only address what is apparent, but possible occult involvement of neighboring structures. Incisions should be placed in a way that allows the surgeon the flexibility to extend the planned resection. If possible, entrance should preserve tissues that can be used to treat surgical complications (e.g. preserving muscle for later use as a muscle flap). The exposure should allow for proximal and distal control of neighboring vessels, the use of cross table ventilation and the urgent use of cardiopulmonary bypass. Complete resection (removing all gross and microscopic disease) is of paramount importance, as the survival of patients is severely compromised by a positive surgical margin. While positive margins are an unfortunate reality to cancer surgery, every effort should be made to estimate the likelihood that a negative surgical margin can be obtained. At times this involves an exploratory phase of the resection (occasionally a minimally invasive approach to start) in order to assess the extent of local involvement (because imaging is notoriously inaccurate for determining the extent of local invasion). Finally the multi-disciplinary team must attempt to select patients that are less likely to develop early systemic failure, as these patients will not benefit from resection. This is of course not knowable with any degree of certainty but an estimate is helpful. Patients should undergo a thorough staging evaluation (brain imaging, PET scanning). While not an absolute contraindication for surgical resection, surgeons should be cognizant of other staging parameters that further compromise the patient’s potential for long-term survival. Most notably this would include the patient’s mediastinal lymph node status. The presence of mediastinal lymph node metastases (N2) is a further indication of the patient’s risk for systemic failure, and is an overall poor prognosticator. While prognosis does not alone define treatment, the patient’s overall prognosis should be considered when attempting to justify surgical risk (which is typically increased for T4 tumor resection). For this reason, it is recommended that surgeons refrain from resecting of T4 tumors associated with N2 disease as their default approach, and rather develop a strategy that attempts to allow patients to declare their potential for early failure. One strategy would be to offer the patient curative-intent nonsurgical therapy (chemoradiation) and observe the patient for a “local only” recurrence. In conclusion, surgical resection of T4 tumors is reasonable and effective in highly selected NSCLC patients. The onus is on surgeons and multidisciplinary care teams to attempt to identify the patients most likely to benefit and least likely to be harmed by surgery.
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