Author of

• 25937

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  P1.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 949)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26782

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    P1.17-08 - Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer (ID 12804)

    16:45 - 18:00  |  Author(s): Federica Oro
    • Abstract

    Background
    

    Radiation with platinum-based doublet chemotherapy is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic alterations are associated with response to therapy.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation, who had undergone tumor molecular profiling through an institutional next-generation sequencing platform. This platform is an FDA-approved, targeted-DNA-sequencing panel that contains 341 (now expanded to 468) somatic mutations and other genetic alterations. Basic patient and tumor characteristics, clinical outcomes including loco-regional recurrence, distant recurrence, and overall survival, were collected. Overall and recurrence-free survivals were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate association between clinical outcome and genetic alterations.

    4c3880bb027f159e801041b1021e88e8 Result
    

    We identified 110 patients with stage III NSCLC who were treated with definitive radiation between 2013 and 2017 and underwent tumor molecular profiling. Fifty-one patients (46%) had stage IIIA disease and 59 patients (54%) had stage IIIB disease. Median radiation dose delivered was 60Gy in 30 fractions (range 48.6Gy to 74Gy). Either concurrent or sequential chemotherapy was given in 104 patients (95%) with 83 patients (75%) receiving concurrently. One patient received induction crizotinib and one patient died before start of chemotherapy. With a median follow-up time of 15.3 months, the median overall survival was 31.2 months. Several genetic mutations were significantly associated with worse overall survival after therapy, including AKT2 any mutation (Hazard ratio 13.71, p<0.001), KMT2C truncating mutations (HR 13.42, p<0.001), KMT2D truncating mutations (HR 6.97, p<0.001), ARID1A frameshift mutations (HR 8.54, p<0.001), and FLT1 any mutation (HR 6.62, p<0.001). These genes were also associated with increased loco-regional recurrence. Mutation in the PIK3C2G gene was significantly associated with improved overall survival. Association of other common genetic alterations such as EGFR mutation with response to therapy was not observed.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    This study coupled multiplex targeted sequencing with clinical outcome information to identify several potential genetic predictors of response to chemotherapy and radiation in locally advanced NSCLC. KMT2C and KMT2D encode two subunits of a histone methyltransferase, and mutations of KMD2 have been shown to correlate with worse survival in locally advanced and advanced NSCLC patients. Further studies including in vitro validations are necessary to confirm the findings.

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