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R. Pasquale



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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      57P - Targeted sequencing of plasma-derived cfDNA in patients with metastatic NSCLC (ID 557)

      12:30 - 13:00  |  Presenting Author(s): R. Pasquale

      • Abstract
      • Slides

      Background:
      Circulating cell free DNA (cfDNA) is an alternative to tumor tissue for molecular profiling in non-small cell lung cancer (NSCLC). Next generation sequencing (NGS) with targeted panels can concurrently evaluate multiple actionable mutations.

      Methods:
      NGS analysis was performed on tissue samples with the Oncomine Solid Tumour DNA kit, while plasma samples were analyzed with the Oncomine Lung cfDNA Assay. Droplet Digital PCR (ddPCR) was performed with the QX200 System to solve discordant cases.

      Results:
      We performed NGS analysis of tumor samples and matched cfDNA obtained from 102 patients with metastatic NSCLC before systemic treatment. NGS detected EGFR mutations in 21/25 plasma samples from EGFR-mutant patients (sensitivity 84%), and in 3/77 samples from EGFR wild type (wt) patients (specificity 96.1%), with a concordance rate of 93.1%. Analysis with ddPCR confirmed in plasma samples the absence of EGFR variants in false-negative cases according to NGS; in the 3 cases with EGFR mutant-plasma and wt-tissue, ddPCR confirmed the presence of EGFR mutations at low allelic frequency in both plasma and tissue samples, therefore confirming the specificity of NGS analysis. We also evaluated in the cohort of 77 EGFR wt tumors the concordance between tumor and plasma for the mutations in genes other than the EGFR covered by both NGS panels. The mean concordance was low (57.3%). In particular, a high discordance among KRAS mutations was observed. Out of 11 cases with KRAS mutations in tissue, only 3 showed also KRAS mutations in plasma. Analysis with ddPCR identified KRAS mutations in the cfDNA from 4/5 available samples that were negative by NGS, suggesting a low sensitivity of the panel for RAS mutations. In addition, NGS analysis revealed KRAS mutations in 3 cases that were negative on tissue. These variants were validated by ddPCR, confirming the specificity of NGS analysis and suggesting tumor heterogeneity for these variants.

      Conclusions:
      Our study showed that plasma-NGS is a suitable method for EGFR genotyping in NSCLC. Relatively low sensitivity and tumor heterogeneity might limit the ability of NGS to identify driver alterations other than EGFR variants.

      Clinical trial identification:


      Legal entity responsible for the study:
      Istituto Nazionale Tumori “Fondazione G. Pascale”- IRCCS, Naples, Italy

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.

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