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A. Alizadeh



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    MA17 - Genetic Drivers (ID 409)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      MA17.07 - Circulating Tumor DNA Detects Minimal Residual Disease and Predicts Outcome in Localized Lung Cancer (ID 5388)

      15:02 - 15:08  |  Author(s): A. Alizadeh

      • Abstract
      • Slides

      Background:
      CT imaging is standard-of-care for surveillance following definitive lung cancer therapy but is complicated by difficulties in distinguishing recurrence from treatment-related fibrosis and inability to detect microscopic disease. CAPP-Seq is a novel blood-based assay that uses next-generating sequencing to quantitate circulating tumor DNA (ctDNA). We performed a prospective study to compare disease surveillance by CAPP-Seq to CT imaging after definitive treatment for localized lung cancer.

      Methods:
      We prospectively enrolled 34 patients treated definitively for non-metastatic primary lung cancer at Stanford University between June 2010 and September 2015. Our cohort included 22 (64.7%) patients with stage III, 6 (17.6%) patients with stage II and 6 (17.6%) patients with stage I disease. All patients received pre-treatment evaluation by thoracic CT and PET/CT scans as well as ctDNA quantitation by CAPP-Seq. Twenty-one (61.8%) patients were treated with conventionally fractionated radiotherapy, 8 (23.5%) with hypofractionated radiotherapy, 3 (8.8%) with surgery, and 2 (5.9%) with both surgery and radiotherapy. Twenty-five (73.5%) patients received platinum-based doublet chemotherapy. Following treatment completion, patients underwent disease surveillance by CT scans and CAPP-Seq every 3-6 months. CT scans were evaluated using RECIST v1.1. CAPP-Seq was performed at each time point as previously described (Newman et al, Nature Medicine 2015 and Nature Biotechnology 2016).

      Results:
      A total of 222 scans and 107 plasma samples were analyzed. Median follow-up time was 21.1 months and median overall survival was 30.0 months. Eighteen (52.9%) patients progressed based on RECIST criteria and CAPP-Seq detected ctDNA at or before the time of RECIST progression in all patients (18 of 18; 100%) with a lead-time of 121 +/- 39 days (mean +/- SEM). For 13 of 16 (81.3%) evaluable patients who progressed, ctDNA was detected at the first time-point after completion of all treatment (median 2 months post treatment), indicating detection of minimal residual disease. Two-year overall survival for patients with detectable post-treatment ctDNA was 25.3% versus 92.9% for those with no detectable post-treatment ctDNA (p=0.0003, HR=6.8, 95% CI=2.6-17.9). This difference remained significant in multivariate models controlling for stage, age, sex, and tumor volume (P=0.01).

      Conclusion:
      We found that noninvasive ctDNA profiling appears to be useful for evaluating response to lung cancer treatment. Quantitation of ctDNA allowed identification of minimal residual disease, which was strongly associated with outcome. These results suggest that ctDNA assessment after definitive intent treatment could potentially be used to guide risk-adapted treatment strategies for localized lung cancer.

      Information from this presentation has been removed upon request of the author.

      Information from this presentation has been removed upon request of the author.