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Anne Traynor



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    P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.15-12 - Real World Applications of Next-Generation Sequencing of Non-Small Cell Lung Cancer in the Veteran Population (ID 12509)

      16:45 - 18:00  |  Author(s): Anne Traynor

      • Abstract

      Background

      Population studies to date have demonstrated decreased rates of driver mutations in non-small cell lung cancer (NSCLC) for veterans with prior tobacco use who receive care at Department of Veterans Affairs (VA) facilities. Causes of this reduced rate have not been identified, but may result in underutilization of broadly based genetic tumor profiling. The VA recently expanded next-generation sequencing (NGS) to include both tissue and liquid biopsies for comprehensive genetic profiling for patients (pts) with advanced malignancy. Herein, we describe clinical utility of NGS from our retrospective cohort of a rural-based NSCLC veteran population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective cohort analysis of 79 veterans with metastatic NSCLC from 07/2015-04/2018. A trainee-initiated quality improvement initiative in 07/2017 disseminated education at the VA facility about the role of NGS testing for non-squamous NSCLC, with support from the University of Wisconsin Precision Medicine and Molecular Tumor Board. Baseline demographics, time to tissue biopsy, and genetic tumor profiling were analyzed; clinical outcome data were collected including overall survivial and progression-free survival.

      4c3880bb027f159e801041b1021e88e8 Result

      As expected, the cohort was predominantly male (91.1%), with tobacco use (median 45 pk-yrs, 95% >5 pk-yrs) and median age 69 yrs. For molecular profiling, 52% had sufficient tissue at metastatic diagnosis, 20% underwent repeat biopsy within 30 days, 17% underwent biopsy after 30 days, and 11% presented with comorbidity resulting in empiric or palliative management. After implementation of the quality improvement project, the frequency of genetic profiling increased compared to pre-expanded NGS availability in the following targets: EGFR (59% v. 90%), ALK (65% v. 90%), ROS1 (35% v. 90%), and BRAF (8% v. 60%). Actionable targets were identified in EGFR 15.4% (5/39 pts), ALK (1/41), ROS1 (1/24), and BRAF (1/11); additional mutations in NTRK1, NTRK3, ERBB2, and FGFR1 were detected.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary results demonstrate that the availability and use of NGS was associated with increased rates of comprehensive genetic profiling in a largely rural veteran population. Ongoing work will expand this retrospective cohort to more thoroughly characterize barriers to diagnosis and target-specific frequency over historical advances in precision oncology. We will review how these genetic profiles may offer both prognostic and predictive value by reporting clinical outcomes between targeted therapy and early applications of immunotherapy within the veteran population.

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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-08 - Identifying Resistance to Immune Checkpoint Inhibitors by Screening for PD-L1 and MHC I Expression on CTCs in Pts with NSCLC (ID 14173)

      12:00 - 13:30  |  Author(s): Anne Traynor

      • Abstract
      • Slides

      Background

      PD-L1 expression on tumor predicts benefit to immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC. However, there are a significant number of patients whose tumor test positive for PD-L1 expression that do not derive benefit from ICIs, suggesting the existence of intrinsic resistance mechanisms. PD-L1 blockade aims to trigger tumor cell recognition and lysis by CD8+ T cells, but this process requires concordant expression of MHC I by tumor cells. Recently, MHC I negativity was observed in 49% of patients with lung carcinoma, and correlated with a lack of CD8+ T cell infiltration, emphasizing the importance of screening for MHC I in combination with PD-L1.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      For the purposes of both screening and the detection of acquired resistance, we developed a minimally invasive diagnostic test using Circulating Tumor Cells (CTCs). CTCs were captured and stained on the ExtractMax system (Gilson, Inc.) with Exclusion-Based Sample Processing (ESP) technology (Salus Discovery, LLC). With automation, the ExtractMax simplifies complex multi-step procedures, reduces variability, and ensures gentle manipulation of rare cell targets for optimal yield and viability.

      4c3880bb027f159e801041b1021e88e8 Result

      A range of PD-L1 and MHC I expression levels were detected on CTCs captured from a cohort of patients with NSCLC, with two patients showing no MHC 1 expression and all others with heterogeneous expression of MHC 1. PD-L1 expression was variable across all samples tested with subset of patients with PD-L1 positive CTCs but MHC I negative, suggesting intrinsic resistance to PD-L1 targeted therapies.

      abstract_14173.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This data supports the feasibility of using an automated CTC processing system to detect and monitor PD-L1 and MHC I expression in patients with NSCLC. Ongoing efforts include expanding this patient cohort in larger clinical trials and transitioning this test into a clinical laboratory testing facility for regulatory approval and use as a clinically actionable diagnostic tool.

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