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Seo Ree Kim



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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-42 - Highly Sensitive Sel-CapTM Lung Cancer Panel NGS for Detection of Tumor-Derived EGFR Mutations in Plasma Cell-Free DNA in Lung Cancer (ID 1197)

      10:15 - 18:15  |  Author(s): Seo Ree Kim

      • Abstract

      Background

      Next-generation sequencing is a genetic analysis platform for multiple analysis and large-scale analysis. Sensitivity is limited by methods for detecting cancer mutations that are contained at low rates in blood.

      With two highly sensitive detection techniques for genetic alterations, we evaluated their diagnostic value for tumor-derived EGFR mutations in plasma cell-free DNA (cfDNA) and measured concordance rate of activating EGFR mutations between cfDNA and tumor tissue.

      Method

      We conducted this study using FFPE tissue and plasma samples which were donated from NSCLC patients (N=316) between 2011 and 2013 and stored in the Human-derived Biomaterials Bank in Seoul St. Mary's Hospital. Meanwhile, we prospectively collected plasma samples simultaneously when tumor tissue was taken out by surgery. We also collected peripheral blood just before administration of EGFR TKIs and each time imaging study was done during the administration of EGFR TKIs. We analyzed activating EGFR mutations in both cfDNA and tumor tissues using PNAclamping, Cancer panel and Sel-CapTM Lung Cancer Panel.

      Result

      The sensitivity and specificity of three detection techniques, PNAclamp, cancer panel and Sel-CapTM Lung Cancer Panel NGS for EGFR mutations in tumor tissues were more than 90% in all.

      In particular, EGFR T790M was found not only in the patients acquiring drug resistance approximately 10-12 months following the administration of 1st or 2nd generation EGFR TKIs, but also in the patients in whom EGFR TKI was continuously maintained over 30 months. The sensitivity of Sel-CapTM Lung Cancer Panel NGS for EGFR exon19 deletion and exon21 L858R in cfDNA was 76.2% and 61.1%, respectively. In addition, the sensitivity for double mutation of 19del and T790M was about 30% higher compared to that of cancer panel sold domestically (2/20, 10.0% vs. 9/20, 45.0%), suggesting that Sel-CapTM Lung Cancer Panel NGS enables to detect EGFR mutation up to 0.1% in plasma cfDNA. As a result of tracking of outcomes of EGFR TKIs treatment over time for patients with low frequency of EGFR mutations, we found that 1st or 2nd generation EGFR TKIs were switched into 3rd generation EGFR TKIs on the basis of disease progression on radiologic imaging, when an average of 6.8 months (0.2-25.4 months) elapsed from the first detection time of T790M in cfDNA. The presence of T790M in peripheral blood harvested periodically from patients receiving EGFR TKIs was initially identified about 3-5 months ahead of disease progress assessed by imaging study.

      Conclusion

      With regard to the detection of EGFR mutations in lung cancer patients, Sel-CapTM Lung Cancer Panel NGS platform showed superior sensitivity to conventional NGS-based cancer panels as well as higher concordance rate between tumor tissues and plasma cfDNA. In longitudinal plasma cfDNA samples isolated from periodic liquid biopsies, quantitative changes of EGFR mutation were found to be significantly correlated to tumor response by EGFR TKIs. Our data suggest that Sel-CapTM Lung Cancer Panel NGS is a highly sensitive diagnostic platform for detection of EGFR T790M induced by long-term administration of EGFR TKIs and for determining when 3rd generation EGFR TKI be begun.