Virtual Library

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    ORAL 22 - Moving Beyond a Smoking Related-Cancer to the Young, Never-smokers and Inherited Disease (ID 117)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 8
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      ORAL22.05 - The Genomics of Young Lung Cancer Study (ID 503)

      B.J. Gitlitz, D. Morosini, A. Sable-Hunt, B.J. Addario, M.B. Jennings, S. Novello, T. Vavala, S. Mach, C. Jones, G.R. Oxnard

      • Abstract
      • Presentation
      • Slides

      Background:
      Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis (< 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration. Our ALCMI study prospectively characterizes the somatic and germline genomics of young lung cancer (GYLC). Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for further studies of heritable and environmental lung cancer risk factors.

      Methods:
      Accrual opened July 2014. Patients are eligible if they were diagnosed with bronchogenic lung cancer less than age 40. A study website allows for virtual consenting so patients can participate remotely from anywhere in the world; and use social media to share our trial. We have an integrated data and bio repository that allows for seamless communication and completion of study activities like remote consenting and routing of blood and tumor specimens. We have defined 7 genomic alterations of interest based on the Lung Cancer Mutational Consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). We aim to demonstrate that the prevalence of targetable genomic alterations will be greater in our population compared to the LCMC and have powered our study to show an increase from 35% to 50%; and an improvement in use of targeted therapy from 22% to 40%. On study subjects without a known genotype will undergo comprehensive genomic profiling with the FoundationOne test to ensure that all of these genes have been tested. Subjects with advanced adenocarcinoma who are wild type for all 7 genes will receive additional genomic profiling using the FoundationOne Heme test; with the goal of identifying novel oncogenic drivers. Additional investigational genomics will include blood for germline analysis and plasma genomics. All on study genomic analysis is at no cost to the participant.

      Results:
      Preliminary results of the first 33 subjects show: Average age at diagnosis: 33 years; Range 22-39; Histology: adenocarcinoma n=29, squamous cell n=4; Stage at diagnosis: stage 4 n=26 (79%) stages 1-3 n=7 (21%). Of those with stage 4 adenocarcinoma (n=24); 18:24 (75%) have either an ALK re arrangement n=10 (42%), an EGFR activating mutation n=5 (21%) or a ROS1 fusion n=3 (13%).

      Conclusion:
      The trial is currently accruing (NCT02273336) https://www.openmednet.org/site/alcmi-goyl. We have accrued patients from the USA, Europe and Australia. Thus far in our prospective series those diagnosed with primary NSCLC < age 40 tend to have stage 4 adenocarcinoma. Preliminary results exceed our statistical expectation with 75% of our metastatic adenocarcinoma patients having an actionable mutation. We plan on presenting data for the first time at WCLC-2015 on the first 50 subjects. (Study, supported by grants from BJALCF, Beth Longwell Foundation, Peter Barker Foundation, Genentech, Schmidt Legacy Foundation, and Upstage Lung Cancer)

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    PRC 03 - Press Conference 3 (ID 198)

    • Event: WCLC 2015
    • Type: Press Conference
    • Track: Other
    • Presentations: 8
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      Abstract – The Genomics of Young Lung Cancer Study - Dr. Barbara Gitlitz, Associate Professor of Clinical Medicine at USC Keck School of Medicine, Los Angeles (ID 3632)

      B.J. Gitlitz

      • Abstract
      • Presentation

      Abstract not provided

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    OA04 - Epidemiology and Prevention of Lung Cancer (ID 370)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Epidemiology/Tobacco Control and Cessation/Prevention
    • Presentations: 8
    • Now Available
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      OA04.07 - Clinical Characteristics of Lung Adenocarcinoma in the Young: Results from the Genomics of Young Lung Cancer Study (Now Available) (ID 5578)

      B.J. Gitlitz, A.H. Wu, M. Bittoni, B.J. Addario, A.L. Sable-Hunt, M.B. Jennings, S. Novello, T. Vavala, R. Chen, D. Morosini, G.R. Oxnard, S..L. Park

      • Abstract
      • Presentation
      • Slides

      Background:
      Background: Lung cancer is increasingly recognized as a heterogeneous disease comprised of genomically defined subtypes with distinct targetable genomic alterations. However, it is unknown whether established lung cancer risk factors differ between these genomically distinct subtypes. In this study of the genomics of young lung cancer (GoYLC), we present preliminary results of lifestyle risk factors by specific genomic alteration to better characterize lung cancer in the young.

      Methods:
      Methods: Beginning in July of 2014, patients diagnosed with a bronchogenic lung cancer under the age of 40 were recruited to the GoYLC study. Informed consent was obtained in-person and virtually (online), allowing patients to participate globally, regardless of proximity to study sites (https://www.openmednet.org/site/alcmi-goyl). To date, this study has accrued a total of 101 cases, of which 85 are adenocarcinoma (AC). Stage 4 AC is the focus of this analysis.

      Results:
      Results: Among the 63 stage 4 AC cases, the most common genomic alterations were ALK rearrangements (n=28; 44% of stage 4 AC cases) and EGFR mutations (n=17; 27%) while the other genomic alterations (n=18; 29%) include ROS1, BRCA2, HER2, P53, RET and ATM. The prevalence of active smoking and/or exposure to passive smoking was highest among those with ALK (64%), intermediate for those with EGFR (47%) and lowest for those with other genomic alterations (39%). However, the prevalence of only active smoking was lowest among those with ALK (28%), followed by EGFR (35%) and highest for those with other genomic alterations (39%). The majority of patients with ALK rearrangements or EGFR mutations reported no family history of lung cancer (82% and 88%, respectively), compared with 67% among those with other genomic alterations.

      Conclusion:
      Conclusion: These preliminary results suggest that lifestyle characteristics and family history in young lung cancer patients may differ by genomic alteration. Passive smoke exposure was more prevalent among those with ALK rearrangements or EGFR mutations. Those with other genomic alterations, albeit, a heterogeneous group, were least likely to be exposed to passive smoking and more likely to be active smokers. We are continuing to enroll participants and are expanding the epidemiologic characterization to all study patients to evaluate if risk factors also differ by tumor stage and histology (Data to be presented). Importantly, this analysis lays the groundwork for the development of our more comprehensive epidemiology of young lung cancer study that may identify potential lifestyle and environmental risk factors related to specific genomic alterations.

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