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V. Hariniv

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-024 - Plasma Circulating cfDNA as a Potential Biomarker in Clinical Management of NSCLC: Experience of Tata Memorial Hospital, India (ID 7975)

      09:30 - 16:00  |  Author(s): V. Hariniv

      • Abstract

      Circulating cell free tumor DNA (ctDNA) from liquid biopsy is a potential source of tumor genetic material in absence of tissue biopsy for EGFR testing. NSCLC patients with detectable levels of oncogenic driver mutations in peripheral blood are known to be associated with more advanced disease and poorer prognosis. Liquid biopsy was performed on132 NSCLC patients with matched tumor tissue for genomic analysis. An EGFR mutation of one major molecular subtype in NSCLC was performed on massive parallel sequencing. The Study’s primary goals were to: (1) Derive high concordance between tissue biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the EGFR gene. (2) Establish and validate Liquid biopsy as a clinically useful surrogate for tissue biopsy in NSCLC whenever tissue biopsy is unavailable and (3) Treatment monitoring and detection of early recurrence.

      Single gene EGFR mutation analysis was performed on the ctDNA by using ultra deep sequencing on the HiSeq platform. Then custom designed bioinformatics algorithms were used to detect somatic mutations at allele frequencies as low as 0.01%.

      Overall concordance of mutation status between 132 pairs of tissue and plasma ctDNA samples for EGFR mutation status was about 97%. 34% (45/132) of the study subset was EGFR mutated on tissue typing and 31% (41/132) in ctDNA, with 100% specificity, 91.1% sensitivity. Positive predictive value was 100% and negative predictive value was 95.6% - with diagnostic accuracy of 97%. A false negative rate of 3% was observed in this study. 14 out of 132 (10%) samples which had rare Exon19 deletions and complex indels could be confidently detected by NGS methods. 6/31 patients (19%) who could not go for biopsy got the EGFR mutation testing on plasma alone, who were positive for Exon19/ Exon21 hotspot mutations could benefit from targeted therapy. An objective efficacy response rate for Gefitinib was estimated at 74%, with a disease control rate of 95.7%. Median period of follow-up was 13.9 months. Median PFS was 18.933 months (95% CI 11.168-26.198) and overall survival was 78.3%.

      10% of newly diagnosed NSCLC patients could get the additional benefit of targeted therapy, by using the NGS which detected recurrent novel HOTSPOT mutations. Liquid Biopsy based tests will soon be as widespread as “standard” biopsies and imaging techniques, offering invaluable diagnostic, prognostic, and predictive information and would promisingly move from research into clinical practice in lung cancer.