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K. Fong

Moderator of

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    PL01 - Opening Plenary (ID 72)

    • Event: WCLC 2013
    • Type: Plenary Session
    • Track: Prevention & Epidemiology
    • Presentations: 2
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      PL01.01 - 40 Years IASLC (ID 4032)

      F. Hirsch

      • Abstract
      • Slides

      Abstract not provided

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      PL01.02 - You Can Take on the Tobacco Industry and Win (ID 4031)

      N. Roxon

      • Abstract
      • Slides

      Abstract not provided

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    PL03 - Presidential Symposium Including Top Rated Abstracts (ID 85)

    • Event: WCLC 2013
    • Type: Plenary Session
    • Track:
    • Presentations: 8
      • Abstract
      • Slides

      Background
      The main challenge in computed tomography (CT) screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer. Thresholds for nodule size and growth rate, which determine which nodules require additional diagnostic procedures, should be based on the lung cancer probability of the individual.

      Methods
      Diameter, volume and volume-doubling time (VDT) of 9,681 non-calcified nodules detected by CT screening in 7,155 subjects were used to quantify lung cancer probability. Complete coverage on all lung cancer diagnoses was obtained by linkages with the national cancer registry. The nodule management algorithm recommended by the ACCP was evaluated and an improved algorithm, based on lung cancer probability, was proposed.

      Results
      Lung cancer probability was low in subjects with a nodule volume <100mm³ (≤0.7%) or maximum transverse diameter <5mm (≤0.6%) Moreover, probability in these subjects was not significantly different from that in subjects without nodules (0.4%). Lung cancer probability was 0.9-5.8% for nodules with a volume 100-300mm³ or a diameter 5-10mm; the VDT further stratified the probability: 0.0-0.9% for VDTs>600days, 4.0% for VDTs 400-600days and 6.7-25.0% for VDTs<400days. Lung cancer probability was high for participants with nodule volumes ≥300mm³ (8.9-26.1%) or diameters ≥10mm (11.1-26.2%), even with long VDTs. Finally, raising the thresholds for nodule size recommended by the ACCP for an indeterminate result from 4mm to 5mm and for a positive result from 8mm to 10mm, would yield fewer follow-up CT examinations (from 29.8% to 22.2%) and fewer additional diagnostic procedures (from 8.9% to 5.3%) while maintaining the sensitivity at 94.2%.

      Conclusion
      Small nodules (volume <100mm³ or diameter <5mm) are not predictive for lung cancer. Immediate diagnostic evaluation is necessary for subjects with large nodules (volume ≥300mm³ or diameter ≥10mm) and only for subjects with nodules of intermediate size is VDT assessment advocated.

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      PL03.02 - DISCUSSANT (ID 3884)

      C. Berg

      • Abstract
      • Slides

      Abstract not provided

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      PL03.03 - MesoVATS: A multi-centre randomised controlled trial of video assisted thoracoscopic pleurectomy versus talc pleurodesis in malignant pleural mesothelioma (ID 2423)

      R.C. Rintoul, A.J. Ritchie, J. Edwards, D.A. Waller, A. Coonar, E. Lovato, M. Bennett, C. Matthews, V. Hughes, J. Fox-Rushby, L.D. Sharples

      • Abstract
      • Slides

      Background
      Malignant pleural mesothelioma (MPM) incidence is increasing and has no known cure. Non randomised studies suggest that video assisted thoracoscopic (VAT) pleurectomy is effective in controlling pleural effusion and may be associated with increased survival compared to talc pleurodesis.

      Methods
      A multicentre randomised controlled trial of VAT pleurectomy versus talc pleurodesis was undertaken for patients > 18 years with any sub-type confirmed or suspected MPM with a pleural effusion who were fit enough to undergo VAT pleurectomy. Exclusion criteria included previous pleurodesis by any approach. Previous malignancy was permitted if there was no evidence of active disease and MPM had been confirmed. Participants were risk stratified using a modified EORTC prognostic scoring system. Talc pleurodesis was performed via tube thoracostomy or by poudrage at thoracoscopy. VAT pleurectomy involved partial parietal pleurectomy and decortication of the visceral pleura, where appropriate, to achieve lung re-expansion. A total of 196 patients was required to show a survival difference at 1 year of 59% (VAT pleurectomy) versus 37% (talc pleurodesis). Ethical approval was granted by Huntingdon, Cambridge (UK) Research Ethics committee: H02/809; ISRCTN: 34321019; ClinicalTrials.gov NCT00821860.

      Results
      Between 2003 and 2012, 196 patients (120 confirmed, 76 suspected) were randomised across 9 UK centres. 21 cases suspected MPM were subsequently found not to have MPM and excluded (pre-planned in protocol), leaving 87 VAT pleurectomy and 88 talc pleurodesis for the main analysis. Baseline characteristics were similar between the two groups; overall mean age 69 years, 86% men and 75% had known asbestos exposure. Eighty four per cent showed epithelioid disease, 78% were IMIG stage 3/4 and 49% were high risk as per EORTC criteria. The allocated procedure was completed for 73 (83%) talc and 78 (90%) VAT pleurectomy patients. One year survival rates (primary outcome measure) were 57% for the talc group and 52% in the pleurectomy group (hazard ratio 1.03 (95% CI: 0.76, 1.42), p=0.83). Of the secondary outcome measures, pleural effusion was controlled in 37% of talc and 59% pleurectomy patients at one month (p=0.008) and in 57% of talc and 76% pleurectomy patients at 6 months (p=0.04). At 9 and 12 months control of pleural effusion was similar between groups. Median hospital stay was longer in pleurectomy patients (8 days (range 1-31) vs. 6 (range 1-15), p<0.001) and this group had significantly more complications, predominantly prolonged air leak (26% vs. 8%, p=0.009). Based on patients with complete data there was a significant benefit in EQ5D quality of life at 6 months (mean difference 0.08 (95%CI 0.003,0.16), p=0.042) and 12 months (mean difference 0.19 (95%CI 0.05,0.32), p=0.006) in favour of the pleurectomy group. Adjusting for bias due to missing data prior to death reduced the difference in 12 month EQ5D to 0.09 (95%CI -0.04,0.22), p=0.16.

      Conclusion
      MesoVATS showed that VAT pleurectomy significantly improved control of pleural effusion versus talc pleurodesis and improved quality of life. However, overall survival was not increased and the pleurectomy group experienced more complications. Subgroup analyses will investigate which patients benefit most from which intervention. Funded by the BUPA Foundation

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      PL03.04 - DISCUSSANT (ID 3885)

      V. Rusch

      • Abstract
      • Slides

      Abstract not provided

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      PL03.05 - An intergroup randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) chemoradiotherapy (CRT) +/- cetuximab (cetux) for stage III non-small cell lung cancer (NSCLC): Results on cetux from RTOG 0617 (ID 1424)

      J. Bradley, G.A. Masters, C. Hu, G. Blumenschein, J. Bogart, S. Schild, J.M. Michalski, V. Kavadi, Y.I. Garces, S. Narayan, L. Nedzi, C.G. Robinson, R.B. Wynn, R. Paulus, W.J. Curran, H. Choy

      • Abstract
      • Slides

      Background
      The two primary objectives of RTOG 0617 were to compare the overall survival(OS) differences of 1) standard-dose(SD)(60Gy) versus high-dose(HD)(74Gy) radiotherapy (RT) with concurrent chemotherapy(CT); and 2) the addition of cetux to standard CRT. Cetux is a monoclonal Ab targeting EGFR with activity when combined with CT in metastatic NSCLC and head and neck cancer (HNC), and with RT in locally advanced HNC.

      Methods
      This Phase III Intergroup trial randomized pts in a 2 x 2 factorial design. Concurrent CRT included weekly paclitaxel(45 mg/m2) & carboplatin(AUC=2). Pts randomized to cetux received a 400 mg/m2 loading dose on Day 1 followed by weekly doses of 250 mg/m2. All pts were to receive 2 cycles of consolidation CT. This is the initial report of survival outcome based on cetux. The trial was designed for 450 evaluable patients with 80% power and a 1-sided alpha of 0.0125 to detect a 29% reduction in OS failure for each comparison (RT and cetux).

      Results
      544 pts were accrued, and 419 and 465 are eligible for RT and cetux analyses. Median follow up is 18.7 months. Cetux delivery was acceptable in both the concurrent and consolidation phases. Therapy related ≥Grade 3 non-hematologic toxicity was higher in the cetux group; 70.5% vs 50.7% (p<.0001). Grade 4 and 5 events were 35.8% and 28.2%, respectively. Median survival was 23.1 vs 23.5 months, & 18-month OS rates were 60.8% vs 60.2% on the cetux vs non-cetux arms, respectively (p=0.484, HR=0.99), which crossed a protocol-specified futility boundary for early reporting. As previously reported, median survival times and 18-month OS rates for SD and HD arms were 28.7 vs 19.5 months, and 66.9% vs 53.9% respectively (p=0.0007, HR=1.56). There was no significant interaction between RT dose and the use of cetux. The OS rates for the 4 arms of this trial are shown in Table. An H-score analysis, a measure EFGR positivity, is forthcoming.

      Table: Overall Survival Rates with 95% CI (pts accrued while all 4 arms were open)
      Time 60 Gy 74 Gy 60 Gy + Cetux 74 Gy + Cetux
      12m 78.4% (68.9, 85.4) 62.6% (51.7, 71.6) 80.0% (70.8, 86.6) 74.7% (64.9, 82.2)
      18m 67.9% (57.6, 76.2) 52.3% (41.5, 62.0) 67.1% (56.8, 75.5) 58.0% (47.6, 67.1)

      Conclusion
      In pts receiving CRT for Stage III NSCLC, 74 Gy is not superior to and may be worse than 60 Gy in terms of OS. Cetux provides no survival benefit in the setting of CRT for Stage III NSCLC.

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      PL03.06 - DISCUSSANT (ID 3886)

      J. Jassem

      • Abstract
      • Slides

      Abstract not provided

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      PL03.07 - Treatment with Therapies Matched to Oncogenic Drivers Improves Survival in Patients with Lung Cancers: Results from The Lung Cancer Mutation Consortium (LCMC) (ID 2444)

      M.G. Kris, B. Johnson, L. Berry, D. Kwiatkowski, A.J. Iafrate, I. Wistuba, M. Varella-Garcia, W. Franklin, S. Aronson, P. Su, Y. Shyr, D..R. Camidge, L.V. Sequist, B. Glisson, F.R. Khuri, E.B. Garon, W. Pao, C.M. Rudin, J. Schiller, E.B. Haura, M.A. Socinski, K. Shirai, G. Giaccone, M. Ladanyi, K. Kugler, J.D. Minna, P. Bunn

      • Abstract
      • Slides

      Background
      Detecting and targeting the oncogenic drivers EGFR and ALK have transformed the care of patients with lung adenocarcinomas. The LCMC was established to use multiplexed assays to test tumors for alterations in 10 genes and provide the results to clinicians to select treatments and clinical trials matched to the driver detected.

      Methods
      Fourteen LCMC sites enrolled patients with metastatic lung adenocarcinomas and tested their tumors in CLIA laboratories for activating mutations in 10 oncogenic driver genes.

      Results
      Tumors were tested from 1,007 patients for at least one gene and 733 for all 10 genes. An oncogenic driver was found in 466 (64%) of fully-genotyped cases. Among these 733 tumors, drivers found were: KRAS 182 (25%), sensitizing EGFR 122 (17%), ALK rearrangements 57 (8%), “other” EGFR 29 (4%), two genes 24 (3%), HER2 19 (3%), BRAF 16 (2%), PIK3CA 6 (1%), MET amplification 5 (1%), NRAS 5 (1%), MEK1 1 (<1%), AKT1 0. For cases with any genotyping, we used results to select a targeted therapy or trial in 275 (28%). Among 938 patients with follow-up, the median survivals were 3.5 years for the 264 with an oncogenic driver treated with genotype-directed therapy, 2.4 years for the 318 with an oncogenic driver with no genotype-directed therapy, and 2.1 years for the 360 with no driver identified (p<0.0001).

      Conclusion
      Individuals with lung cancers with oncogenic drivers receiving a corresponding targeted agent lived longer than similar patients who did not. An actionable driver was detected in 64% of tumors from patients with lung adenocarcinomas; more than one was present in 3%. Multiplexed testing aided physicians in choosing therapies and targeted trials in 28% of patients. This paradigm for care and research will expand as genotyping becomes more efficient with Next-Gen platforms, additional drivers are identified (i.e.ROS1 and RET), and more targeted drugs become available in the pharmacy and through clinical trials. Supported by HSS NIH NCI 1RC2CA148394-01. Trial Registered with Clinicaltrials.gov: NCT01014286.

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      PL03.08 - DISCUSSANT (ID 3887)

      B. Solomon

      • Abstract
      • Slides

      Abstract not provided

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Author of

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    C - Inaugural Cochrane Workshop (ID 78)

    • Event: WCLC 2013
    • Type: Other Sessions
    • Track: Other Topics
    • Presentations: 2
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      C.00 - Inaugural Cochrane Workshop (ID 4023)

      K. Fong

      • Abstract

      Abstract
      The Cochrane Collaboration is an international, independent, not-for-profit organisation of over 28,000 contributors from more than 100 countries, dedicated to making up-to-date, accurate information about the effects of health care readily available worldwide. Cochrane contributors work together to produce systematic reviews of healthcare interventions, known as Cochrane Reviews, which are published online in The Cochrane Library. Cochrane Reviews are intended to help providers, practitioners and patients make informed decisions about health care, and are the most comprehensive, reliable and relevant source of evidence on which to base these decisions. Over 5,000 Cochrane Reviews have been published so far, online in the Cochrane Database of Systematic Reviews, part of The Cochrane Library. The Collaboration also prepares the largest collection of records of randomised controlled trials in the world, called CENTRAL, published as part of The Cochrane Library. Work from the Cochrane Collaboration is internationally recognised as the benchmark for high quality information about the effectiveness of health care. The Collaboration believes that effective health care is created through equal partnerships between researcher, provider, practitioner and patient. Cochrane Reviews are unique because they are both produced by, and are relevant to, everyone interested in the effects of human health care. Based on the best available evidence, healthcare providers can decide if they should fund production of a particular drug. Practitioners can find out if an intervention is effective in a specific clinical context. Patients and other healthcare consumers can assess the potential risks and benefits of their treatment. The Cochrane Collaboration's contributors are a mix of volunteers and paid staff who are affiliated to the organisation through Cochrane entities: healthcare subject-related review groups, thematic networks (called 'fields'), groups concerned with the methodology of systematic reviews, and regional centres. Many are world leaders in their field of medicine, health policy, research methodology or consumer advocacy, and our entities are situated in some of the world's finest academic and medical institutions. The Cochrane Collaboration is named after Archie Cochrane (1909-1988), a British epidemiologist, who advocated the use of randomised controlled trials as a means of reliably informing healthcare practice. The Collaboration is an independent, not-for-profit organisation, funded by a variety of sources including governments, universities, hospital trusts, charities and personal donations. The Collaboration is registered as a charity in the United Kingdom. To tie the organisation together, there are a number of overarching structures, led by the Steering Group, which provides policy and strategic leadership for the organisation. Members of this group are democratically elected from, and by, contributors. The Cochrane Operations Unit, is based in Oxford, UK, which manages the financial, legal and administrative work of the organisation, led by the Chief Executive Officer of the Collaboration; and a Cochrane Editorial Unit, based in London, UK, which supports Cochrane Review production, editorial processes, and training and methods development, led by the Editor in Chief of The Cochrane Library. There are annual conferences, known as "Colloquia", which are open to everyone. Colloquia are designed to bring people together in one place to discuss, develop and promote our work, and to shape the organisation's future direction In addition to the core mission of producing Cochrane Reviews, contributors are involved in a number of related activities, including advocacy for evidence-based decision-making, providing training in Cochrane Review preparation, developing the methodology for preparing reviews, and translating them from English into a variety of different languages. This session includes providing an introduction to developing a Cochrane Review and is kindly supported by the Cochrane Lung Cancer Review Group, based in Barcelona Spain (website ) and uses high quality training materials developed by the Cochrane Collaboration (grateful acknowledgement of for allowing the use of the training materials) delivered by volunteer Cochrane Collaborators. The session will address topics including; Introduction to systematic reviews, Writing a Cochrane protocol, Searching for studies, Collecting data, Risk of bias, Meta-analysis, Types of data, Heterogeneity, Analysing data and Interpreting results Other training resources include Online Learning Modules as part of a self-directed learning initiative of The Cochrane Collaboration. They provide an introduction to the core skills and methods required for new authors of Cochrane systematic reviews of interventions. The modules are intended to complement other learning opportunities such as face-to-face workshops and webinars, and the guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions.

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      C.03 - Defining a Review Question (ID 803)

      K. Fong

      • Abstract
      • Slides

      Abstract not provided

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    P3.01 - Poster Session 3 - Cancer Biology (ID 147)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.01-011 - Heterogeneity in tumour content and necrosis in primary lung cancers: Implications for molecular analysis (ID 3326)

      K. Fong

      • Abstract

      Background
      Lung adenocarcinoma (AC) and squamous cell carcinoma (SCC) tumours have a large variance in tumour cell content. This heterogeneity is a concern for genomic studies, as it is difficult to distinguish mutational differences between tumour and non-tumour if low percentage tumour is used for analysis. In addition to this, tumour samples are affected by the amount of necrosis present, as the overall number of viable cells is decreased. We assessed tumour and necrotic content in lung tumour specimens from AC and SCC patients and aimed to identify possible implications for the suitability of these samples in molecular characterisation studies using next generation sequencing technology.

      Methods
      Lung tissue specimens were collected during the period of 1990 to 2013 from patients at The Prince Charles Hospital who consented to donate their surgically resected lung tissues for research. Tissues were macroscopically dissected, snap frozen in liquid nitrogen and stored at -80°C. A tissue section was taken and stained with haematoxylin and eosin (H&E) for two pathologists to independently assess tumour cell and necrotic content. Tumour cell content (TC) in each specimen was scored as percentage of viable cells as seen on the H&E slide, where necrotic content (NC) was recorded as a percentage of the whole slide section. Statistics were calculated using SPSS v21 software. Tumour specimens screened for eligibility to The Cancer Genome Atlas sequencing project are presented here.

      Results
      Tumours from 62 AC and 104 SCC subjects were scored (specimen characteristics in Table 1). Scoring between the two pathologists was highly correlated, with a high intraclass reliability (0.94 and 0.96 for TC and NC respectively).

      Table 1: Clinical and Pathological Characteristics of Specimens
      AC SCC
      Number of Specimens 384 609
      Number of Males/Females 36/26 84/20
      Median Specimens per Subject 4 4
      Range of Specimens per Subject 1-25 1-27
      Median TC 35% 30%
      Range of TC 0-88% 0-90%
      Median NC 0% 6%
      Range of NC 0-90% 0-100%
      Median Age 62 yrs 68 yrs
      Range of Age 45-85 yrs 46-91 yrs
      Median Smoking Pack Years 40 56
      Range of Smoking Pack Years 0-115 0-158
      TC varied from 0-~90% for both subtypes. Comparing AC and SCC, the median TC was higher in AC than SCC (35% vs 30% respectively, p<0.05). NC varied from 0-~100%, but was generally low. The median NC was statistically significantly different between AC and SCC (0% and 6% respectively, p<0.001). TC was weakly correlated with NC (Spearman Rank r = 0.32, p<0.01). There were no clinically important correlations between smoking pack years, gender or age with TC and NC of specimens.

      Conclusion
      Lung AC and SCC specimens are heterogeneous in terms of TC and NC. Therefore, only a small proportion of resected lung cancer specimens meet the criteria required for massively parallel sequencing projects that require high quality tumour DNA and RNA (ie low NC) and relatively low stromal contamination (ie high TC).