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W. Weder

Moderator of

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    HOD3 - Tuesdays Highlights of the Day - Surgery, Staging, Imaging and Pulmonary (ID 227)

    • Event: WCLC 2013
    • Type: Highlight of the Day Session
    • Track: Imaging, Staging & Screening
    • Presentations: 2
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      HOD3.1 - Surgery and Staging (ID 4046)

      07:00 - 08:00  |  Author(s): H. Date

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      HOD3.2 - Imaging and Pulmonary (2 Day Coverage) (ID 4047)

      07:00 - 08:00  |  Author(s): P.E. Postmus

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    O09 - General Thoracic Surgery (ID 100)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Surgery
    • Presentations: 8
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      O09.01 - Sites, Symptoms, CT Scan Findings and Survival in Patients with Recurrence After Curative-Intent Surgical Resection for Stage I Lung Adenocarcinoma (ID 2907)

      16:15 - 17:45  |  Author(s): H. Ujiie, D. Buitrago, K. Kadota, J. Huang, W.D. Travis, V.W. Rusch, P.S. Adusumilli, N.P. Rizk

      • Abstract
      • Presentation
      • Slides

      Background
      The purpose of this study is to examine the patterns of recurrence for stage I lung adenocarcinoma and to identify clinicopathologic factors associated with post-recurrence survival (PRS).

      Methods
      We performed a retrospective review of 1027 patients with stage I lung adenocarcinoma who underwent a surgical resection between 1999 and 2009 (median follow-up 35 months). The manner of recurrence detection, either by scheduled CT scan, presentation with new symptoms, or by other means, was noted. Tumors were classified using the new IASLC/ATS/ERS nomenclature and grading as low (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic-predominant), intermediate (papillary-predominant or acinar-predominant), and high (micropapillary-predominant, solid-predominant, colloid-predominant, or invasive mucinous) grade. The Kaplan-Meier method was used to analyze recurrence-free survival (RFS). Log-rank tests and Cox proportional hazard models were used to analyze the association between predictive factors and PRS.

      Results
      Of the 1027 patients with follow-up data available, 151(15%) had recurrent disease (table), five-year RFS was 80%. Of the 151 patients with recurrence, 80 (52%) were detected by a scheduled CT scan (51 locoregional and 29 distant). Symptomatic recurrences were seen in 70 (46%) patients (9 locoregional and 61 distant). Overall, 5-year PRS was 27.8%. On multivariate analysis, recurrences identified by new symptoms (HR, 2.15; 95% CI, 1.36- 3.40; p=0.001), a recurrence free interval ≤ 24 months (HR, 2.52; 95% CI, 1.31- 4.84; p=0.006), and tumors with high architectural grade (HR, 1.69; 95% CI, 1.07- 2.67; p=0.024) and vascular invasion (HR, 1.79; 95% CI, 1.14- 2.81; p=0.012) were significantly associated with a worse PRS (Figure).Figure 1Figure 2

      Conclusion
      Our study demonstrates the recurrence patterns in patients who underwent surgical resection for stage I lung adenocarcinoma. We identify a symptomatic recurrence, a recurrence-free interval ≤ 24 months, high architectural grade, and vascular invasion, as independent factors associated with worse post recurrence survival.

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      O09.02 - Clinicopathological characteristics and surgical results of lung cancer patients aged up to 50 years: the Japanese Lung Cancer Registry Study 2004 (ID 83)

      16:15 - 17:45  |  Author(s): M. Inoue, M. Okumura, N. Sawabata, E. Miyaoka, H. Asamura, I. Yoshino, H. Tada, Y. Fujii, Y. Nakanishi, K. Eguchi, M. Mori, H. Kobayashi, K. Yokoi

      • Abstract
      • Presentation
      • Slides

      Background
      Since the incidence of lung cancer death increases from 50 years-old, the surgical results of young lung cancer patients remains unclear.

      Methods
      Seven hundred and four patients with lung cancer, aged up to 50 years, were enrolled from among the 11,663 patients registered in the Japanese Lung Cancer Registry Study 2004, and their clinical data were compared with those of 10959 patients older than 50 years.

      Results
      In the young/old groups, pneumonectomy was performed in 5.7%/3.2%; adjuvant therapies were given preoperatively in 10.4%/4.7% (p<0.001) and postoperatively in 31.4%/24.5% (p<0.001). The proportions of patients with p-stage IIIA and adenocarcinoma histology were higher in the young group. The 5-year overall survival rate (5Y-OS) was 94.8%/86.2% for p-stage IA (p<0.001), 87.0%/73.2% for p-stage IB (p=0.001), 61.0%/61.6% for p-stage IIA (p=0.595), 71.0%/48.4% for p-stage IIB (p=0.003), 49.6%/39.4% for p-stage IIIA (p=0.020), and 80.0%/24.8% for p-stage IIIB (p=0.012); it was 83.5%/80.7% for females (p=0.106) and 75.1%/62.3% for males (p<0.001) in the young/old groups. The postoperative survival was significantly better with all operative procedures in the young group. The 5Y-OS after recurrence was better in the young group (17.9%, p=0.016). In the young group, the 5Y-OS was better in females (83.5%) than in males (75.1%, p=0.002), and for patients with adenocarcinoma (80.3%) than for those with squamous cell carcinoma (68.5%, p=0.013). Age up to 50 years was identified as an independent prognostic factor on multivariate analysis. Figure 1

      Conclusion
      The postoperative survival in lung cancer patients aged up to 50 years was better than that in patients older than 50 years.

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      O09.03 - Quality Indicators in Thoracic Surgery: The importance of process indicators in lung cancer (ID 2034)

      16:15 - 17:45  |  Author(s): G.E. Darling, J. Dickie, R. Malthaner, L. McKnight, Y. Sallay, A. Hunter, Y. Li, R. McLeod

      • Abstract
      • Presentation
      • Slides

      Background
      Outcome after surgery is the result of many components of the care pathway.. The Thoracic Surgery Community of Practice of Cancer Care Ontario developed quality indicators which reflected processes of care as well as outcomes.

      Methods
      A systematic review of the literature identified potential indicators in the care of lung cancer patients which were relevant to thoracic surgery. These were then evaluated using a modified Delphi process. Seventeen indicators were chosen from seven domains: pre-operative assessment, staging, surgery, pathology, adjuvant therapy, surgical outcomes and miscellaneous based on actionability, validity, usefulness, discriminability, and feasibility. Data obtained from administrative databases is reported for 4 process indicators and 3 outcome indicators.

      Results
      Of the 3242 patients diagnosed with Stage I and Stage II non-small cell lung cancer in 2009 and 2010, 2172 (67%) received a surgical consultation and 1524 (47%) underwent resection within 3 months of diagnosis. For the 1075 Stage I and Stage II patients over age 75 only 634 (59%) received a surgical consultation and 322 ( 32%) underwent resection. Of the 2302 patients resected in total (all stages), only 736 (32%) had invasive mediastinal staging(IMS) prior to resection:15% for sublobar resections; 30% for stage I; and 42% for stage II. Surprisingly only 42% of patients with stage III disease had IMS. IMS was also performed in an additional 23% of patients for whom stage data was unavailable. In a similar cohort of patients resected in 2011-2012, only 28% had ≥10 lymph nodes removed at the time of resection but this did not include nodes assessed by IMS. However, for 20% of patients lymph node resection data was not available or could not be determined. Positive resection margins were reported in 7% of patients, however in a further 7% of patients margins could not be assessed. 30 day mortality for lobectomy was 1.9%, reoperation rate was 2.8% (2.0% for same day as resection).

      Conclusion
      Initial results of 7 quality indicators in thoracic surgery identified some quality gaps in processes of care as well as limitations in databases. Evaluation of process indicators allowed feedback to thoracic surgeons and pathologists who identified quality improvement opportunities. Rate of surgical consultation and resection for stage I and II disease was lower than expected as were rates of invasive mediastinal staging especially for patients with stage III disease for whom cytologic or histologic confirmation is recommended. To address variable intraoperative lymph node assessment, systematic lymph node sampling or complete mediastinal lymphadenectomy was recommended to standardize intraoperative lymph node assessment. Quality improvement opportunities for pathologists also included dissection of intralobar lymph nodes, standardization of pathological processing and margin assessment. Feedback of quality indicator data was important in stimulating quality improvement initiatives by thoracic surgeons and pathologists.

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      O09.04 - DISCUSSANT (ID 3921)

      16:15 - 17:45  |  Author(s): H. Pass

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      O09.05 - Intraoperative autostapling cartridge lavage cytology in surgical resection of pulmonary malignant tumors - possible role in preventing local failure (ID 2543)

      16:15 - 17:45  |  Author(s): T. Miyoshi, K. Aokage, G. Ishii, Y. Matsumura, T. Haruki, T. Hishida, J. Yoshida, K. Nagai

      • Abstract
      • Presentation
      • Slides

      Background
      Limited resection of primary lung cancer or sublobar resection of pulmonary metastatic tumor can result in cut-end recurrence. It is important to confirm the absence of tumor cells at the cut-end. Since 2004, all autostapling cartridges used for wedge or segmental resection of pulmonary malignancies are washed with 50 ml saline. Washing saline is centrifuged and the sediment is stained using Papanicolaou’s method and examined for cancer cells during surgery to confirm negative margin. The aim of this study is to evaluate the efficacy of the intraoperative autostapling cartridge lavage cytology in preventing surgical cut-end recurrence.

      Methods
      The intraoperative cytology analysis was performed in 271 patients undergoing wedge or segmental resection for 319 lesions including primary lung cancers and pulmonary metastatic tumors between April 2004 and April 2010. We retrospectively reviewed the clinicopathologic features of patients with positive cytology results and those who developed recurrence at the surgical margins.

      Results
      The median age of the 271 patients at surgery was 67 years (range: 31−92 years). The median size of the 319 lesions was 1.4 cm (range: 0.4−3.5 cm), and there were 149 primary lung cancers and 170 pulmonary metastatic tumors (primary site: 116 colorectal and 54 others). Twenty-two lesions (7%) showed positive cytology results (11 primary and 11 metastatic). In primary lung cancers, tumor size (≧ 21 mm, p = 0.02), moderate to poor differentiation (p < 0.01), vascular invasion or lymphatic permeation (p < 0.01), and visceral pleural invasion (p < 0.01) were significant predictors of a positive result. In contrast, there were no significant predictors in pulmonary metastatic tumors. The cut-ends of the 19 lesions among the 22 positive cytology margin lesions were additionally resected, but those of the remaining 3 lesions were not because of impaired respiratory function. With the median follow-up period of 42 months, surgical cut-end recurrence occurred in 2 of the 19 lesions for which additional resection had been performed (11%, 1 primary and 1 metastatic). Of the 3 lesions for which additional resection was impossible, cut-end recurrence developed in 2 (67%, 1 primary and 1 metastatic). Among the 297 lesions showing negative cytology result, cut-end recurrence occurred in 5 (2%, 4 primary and 1 metastatic).

      Conclusion
      Intraoperative autostapling cartridge lavage cytology in sublobar resection for primary or metastatic lung tumor may be useful in preventing surgical cut-end recurrence.

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      O09.06 - Prognostic factors for long-term survival in non-small cell lung cancer patients with interstitial lung disease (ID 3453)

      16:15 - 17:45  |  Author(s): J. Jeon, Y.T. Kim, Y. Hwang, H.S. Kim, I.K. Park, C.H. Kang

      • Abstract
      • Presentation
      • Slides

      Background
      There is little information about prognosis after pulmonary resections for non-small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD). In this study, we examined the long-term outcome and the factors that affect long-term survival after resection for NSCLC in patients with ILD.

      Methods
      Between September 1996 and May 2011, 71 NSCLC patients were diagnosed as having ILD based on the CT and pathological findings. The extent of ILD on CT was scored visually at the level of 3 cm above the diaphragm as follows: minimal, <2 cm from the subpleura at the base of the lungs; moderate, >2 cm from the subpleura, but less than one-third of the lung area at the base of the lungs; severe, more than one-third of the lung area at the base of the lungs. Various clinical values such as gender, age, preoperative chemotherapy, severity of ILD on CT, preoperative pulmonary function test results, arterial blood gas studies, operative procedure, pathologic stage, cell type, and adjuvant treatment were evaluated using univariate and multivariate analysis.

      Results
      The mean age was 65.9 years, and the majority of patients were male(65:91.5%). In-hospital mortality was 9.9% (7/71). The causes of early mortality included pneumonia (n=4), acute respiratory distress syndrome (n=2), and acute exacerbation of ILD (n=1). The 5-year overall survival rate was 43.1% (stage I: 59.4%, stage II: 41.3%, stage III: 35.0%, respectively). In univariate analysis, the risk factors for long-term mortality were lower preoperative FEV~1~, FVC, severe ILD on CT, presence of pathologic pulmonary fibrosis, and non-squamous cell type. In multivariate analysis, severity of ILD on CT and non-squamous cell type remained as poor prognostic factors.Figure 1

      Conclusion
      Although patients with ILD undergoing pulmonary resection for NSCLC has resulted in a high in-hospital mortality, long-term survival can be expected in highly selected patients. NSCLC patients with severe ILD on CT findings and those with non-squamous cell type should be carefully selected for major pulmonary resection.

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      O09.07 - Phase II Double-blind Randomized trial comparing Posterolateral Thoracotomy versus Nerve Sparing Thoracotomy for lung surgery (PoTNeST) - Impact of preservation of the neurovascular bundle during thoracotomy on post-operative pain (ID 2587)

      16:15 - 17:45  |  Author(s): C.S. Pramesh, S. Jiwnani, P. Ranganathan, V. Patil, G. Karimundackal, V. Agarwal

      • Abstract
      • Presentation
      • Slides

      Background
      Posterolateral thoracotomy has been extensively used for non-cardiac thoracic surgery. Although this procedure provides excellent access for cancer surgery, it is responsible for considerable postoperative pain and contributes to postoperative pulmonary insufficiency. Post-thoracotomy pain has been reported to occur in 10 to 70% of patients. Intercostal nerve injury has been implicated as a major factor in the etiology of post-thoracotomy pain. We performed a study to compare post-thoracotomy pain in patients undergoing posterolateral thoracotomy with and without the preservation of the intercostal neurovascular bundle.

      Methods
      This randomized double-blind phase II trial was carried out in a tertiary-referral cancer centre. We included adult patients undergoing posterolateral thoracotomy for pulmonary resection. Patients were randomized into two groups – standard posterolateral thoracotomy (PoT) where no attempt was made to preserve the intercostals neurovascular bundle or modified nerve-sparing thoracotomy (NeST) which involved preservation of the intercostal neurovascular bundle while opening the intercostal space and closure by drilling holes in the lower rib, thereby avoiding pericostal sutures. All surgeries were performed under general anaesthesia with fentanyl, morphine, diclofenac and paracetamol for intra-operative analgesia. Post-operatively, all patients received round-the-clock paracetamol and diclofenac with an intravenous morphine patient-controlled analgesia pump for additional analgesia. Worst and average pain scores (on a Numerical Rating Scale) and morphine requirements on the first three post-operative days were assessed. Patients and assessors were blinded to study group. Chronic pain was assessed 6 months after surgery using a standard questionnaire. The primary outcome was the mean worst pain score over the first three post-operative days. Secondary outcomes were mean average pain score over the first three post-operative days, morphine consumption and incidence of post-thoracotomy pain at 6 months.

      Results
      We recruited 90 patients between May 2010 and July 2012. Groups were comparable in terms of age, gender, weight and type of surgery. There was no significant difference between the PoT and the NeST group in mean worst pain scores over the first three post-operative days (3.83 versus 3.71, difference 0.12, 99% CI -0.7 to 0.9). Mean average pain scores were also similar between the groups (1.85versus 1.77, difference 0.08, 99% CI -0.4 to 0.6) as was the mean morphine consumption in milligram per kilogram body weight (1.40 versus 1.45, difference of -0.05, 99% CI -0.4 to 0.3). Chronic pain was present in 18 of 39 assessable patients (46.1%) in the PoT group and 17 of 41 assessable patients (41.2%) in the NeST group (difference 4.7%, 99% CI -22.8% to 30.7%).

      Conclusion
      Preservation of the neurovascular bundle during thoracotomy using a modified nerve-sparing approach has no impact on acute or chronic post-thoracotomy pain or analgesic requirements as compared to a standard posterolateral approach.

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      O09.08 - DISCUSSANT (ID 3922)

      16:15 - 17:45  |  Author(s): H. Date

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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Author of

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    MS15 - Extending the Limits of Combined Modality Treatment for NSCLC (ID 32)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Combined Modality
    • Presentations: 1
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      MS15.4 - Surgery after Induction Chemo/Radiation Therapy (ID 529)

      14:00 - 15:30  |  Author(s): W. Weder

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MS16 - ESTS/IASLC Thymic Session (ID 33)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      MS16.3 - Surgery for Thymic Tumours: Outcomes from the ESTS Data Base (ID 532)

      10:30 - 12:00  |  Author(s): W. Weder

      • Abstract
      • Presentation
      • Slides

      Abstract
      Introduction: Thymic tumors are rare malignancies and most of the current literature is composed of single-institutional series collecting small number of patients spanned over short time periods. The European Society of Thoracic Surgeons (ESTS) thymic working group developed a retrospective database among its members collecting patients with thymic tumors submitted to surgical resection between 1990 and 2010. Methods: A total of 2151 patients were collected from 35 Institutions, including 1798 thymomas, 191 thymic carcinomas (TC), and 41 Neuroendocrine Thymic Tumors (NETT)). 1709 patients (89%) received a complete resection. Myasthenia Gravis (MG) was present in 629 patients (35%). Different clinical-pathologic characteristics were analyzed for their impact on survival and recurrence. Primary outcome was overall survival (OS); secondary outcomes were the proportion of incomplete resections, disease-free survival (DFS) and the cumulative incidence of recurrence (CIR). Results: Ten-year OS and DFS rates were 73% and 70%. The risk of mortality increased with age and with the stage. It also increased in the presence of TC, NETT and incomplete resection. Ten-year CIR was 12%. Predictors of incomplete resection included male gender, tumor size, the absence of MG, non-thymoma categories (TC and NETT) and high-risk thymomas (B2-B3). The risk of recurrence increased with tumor size, increased stage and NETT. Finally, our analysis indicates that the overall effect of adjuvant therapy after complete resection on OS was significantly beneficial (p=0.05) using a propensity score. Conclusions: Masaoka stages III-IV, incomplete resection and non-thymoma histology showed a significant impact in increasing recurrence and in worsening survival. The administration of adjuvant therapy after complete resection is associated with improved survival.

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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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      P2.06-002 - Protein tyrosine kinase substrates profiling to detect short-term survivors in early stage lung adenocarcinoma (ID 165)

      09:30 - 16:30  |  Author(s): W. Weder

      • Abstract

      Background
      With existing therapeutic efforts, patients with lung cancer have a poor prognosis. Assessment of tumor size, lymph node status and presence of metastases is currently applied for determining prognosis and treatment modality, but predicted and real outcomes can vary significantly. Biomarkers with reliable prognostic significance are therefore of utmost importance but due to a lack of immediate correlation between levels of protein and their corresponding mRNA, a screen based on the kinase activity become a promising option to circumvent this limitation with the tremendeous advantage of focusing on therapeutically targetable enzymatic activities. Several protein tyrosine kinase inhibitors already clinically approved for the treatment of lung cancer are targeting some of the 400 types of DNA signatures described in silico in the human genome. The aim of this study is to clarify the following hypothesis: Is the in vitro multiplexed tyrosine phosphorylation of substrates a possible approach to molecularly classify the kinome of early stage lung adenocarcinoma biopsies and obtain a diagnostic /prognostic signature correlating with the survival of patients?

      Methods
      We have built a tumor bank of frozen malignant and non-neoplastic lung surgically obtained specimen and recorded all clinical interventions, follow up treatments and outcome for each of our patients. We incubated TNM stage 1 and 2 lung adenocarcinoma kinomes on PamChip®4 microarrays and followed the kinetics of the multiplexed tyrosine phosphorylation for 144 peptides substrates. Image quantification, quality control, statistical analysis and interpretation of data were performed with the BionavigatoR software.

      Results
      We screened 84 paired malignant TNM stage 1 and 2 lung adenocarcinoma and non-neoplastic lung biopsies for the multiplex tyrosine phosphorylation of substrates immobilized on a PamChip®4microarrays. Based on a 76-point ‘response-signature’ we obtained 73 % of correct prediction with a 10 fold cross validation PLS-DA analysis in TNM stage 1 lung adenocarcinoma biopsies. Moreover, we detected 26 peptides substrates significantly more inhibited in kinomes of long-term survivors than in kinomes of the short-term survivors.

      Conclusion
      In frozen biopsies of TNM stage I adenocarcinoma and with a PLS-DA analysis applied to a 76-point ‘response-signature’ we present the feasibility to discriminate between long-term and short-term survivors. Furthermore, the found differences in enzymatic activities in lung biopsies may result in the identification of new targets in future anti lung cancer therapy efforts.