Author of

• 16549

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  P1.02 - Poster Session with Presenters Present (ID 454)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 16560

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    P1.02-011 - Comparison of EGFR and KRAS Mutations in Archival Tissue and Circulating Tumor DNA: The Impact of Tumor Heterogeneity (ID 4504)

    14:30 - 14:30  |  Author(s): I. Bosdet
    • Abstract

    Background:
    In non-small cell lung cancer (NSCLC), circulating tumour DNA (ctDNA) has gained acceptance as a potential alternative to tissue biopsies to identify targetable mutations. Individual ctDNA platforms have varying abilities to detect specific mutations. A prospective, multicenter study was conducted to determine concordance, sensitivity, and specificity of ctDNA genotyping, with archival tissue DNA (atDNA) as the reference standard.
    
    Methods:
    Patients with incurable advanced NSCLC at the BC Cancer Agency were enrolled over 14 months. Next-Generation Sequencing (NGS) and high-throughput multiplex amplification of a 27-gene panel (Raindance) was used for atDNA analysis. Four mL of plasma was collected in Streck (Cell Free DNA BCT) tubes for ctDNA genotyping using the Boreal Genomic OnTarget. Analysis of concordance, sensitivity, and specificity was conducted with atDNA used as the standard.
    
    Results:
    Seventy-six patients were enrolled, median age 66, 33 (44%) male, 69 (91%) metastatic disease, 47 (62%) with primary disease in-situ. Twenty-six EGFR mutations in 22 atDNA samples, and 12 mutations in 11 ctDNA samples were detected, with a concordance of 78%, sensitivity of 39%, and specificity 98%. One EGFR T790M mutation was positive by ctDNA alone. Twenty-one KRAS mutations in 21 atDNA samples were detected. Within this subgroup, 10 ctDNA samples had KRAS mutations with a concordance of 76%, sensitivity of 50%, and specificity of 80%. Fourteen KRAS mutations were detected by ctDNA only. The interval between archival tissue and ctDNA collection, and time between treatment and ctDNA collection, did not significantly impact the rate of concordance (p> 0.05).
    
    Conclusion:
    Although the sensitivity is limited, the Boreal Genomic OnTarget ctDNA analysis is specific in identifying clinically relevant EGFR mutations and has acceptable concordance rates between ctDNA and atDNA testing. Targetable EGFR and KRAS mutations were detected in ctDNA but not atDNA, which may reflect site of biopsy, tumor heterogeneity, or technical limitations of assays used. Given the high specificity and non-invasive nature of this test, positive results in EGFR mutations can be used to direct therapeutic decisions, especially accounting for clonal evolution overtime in detection of resistance mutations.