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Jian Ma



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    EP1.12 - Small Cell Lung Cancer/NET (ID 202)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.12-37 - Higher Consistency of Mutations Between Tumor DNA and ctDNA in Small-Cell Lung Cancer Compared to Non-Small Cell Lung Cancer (ID 2060)

      08:00 - 18:00  |  Author(s): Jian Ma

      • Abstract

      Background

      Small-cell lung cancer (SCLC) is an aggressive neuroendocrine lung tumor representing 15% of lung cancers, patients with SCLC usually have a poor prognosis and limited treatment options. This is primarily due to the lack of adequate tumor tissues to assess and delaying therapy to repeat biopsies is often not possible. Circulating cell-free tumor DNA (ctDNA) based test for EGFR mutations in patients with Non-small cell lung cancer (NSCLC) has been approved by US Food and Drug Administration, however, whether it is feasible to perform genomic profiling of ctDNA from SCLC patients still have been lacking. SCLC is characterized by early hematogenous spread, we hypothesized that ctDNA sequencing in SCLC is more comprehensive as a promising biomarkers than that in NSCLC.

      Method

      To analyze the consistency of gene mutation sites between tumor DNA and perepheral blood ctDNA in patients with lung cancer (SCLC and advanced NSCLC), and further explore the feasibility of ctDNA as a clinical tool in SCLC. Paired tumor and blood samples were obtained from systemic treatment naïve patients with SCLC and advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 808 previously annotated genes related to solid tumors.

      Result

      During February 2017 to April 2018, 8 SCLC and 119 advanced NSCLC patients were enrolled from 3 centers. A total of 256 somatic variations were detected in tumor DNA and ctDNA. TP53 and RB1 are the most frequently mutated genes in SCLC patients and mutations occurred most frequently in NSCLC were EGFR , TP53 , KRAS , ALK. In matched tumor DNA and ctDNA, we observed significant higher concordance of mutations in SCLC (90%) compared to NSCLC (65%). Furthermore, the variant allele frequency (VAF) of shared mutations in SCLC highly correlated to each other (r=0.68). In addition, a subset of mutations was exclusively detected in ctDNA, indicating that the genomic landscape derived from ctDNA reflects that from SCLC to a certain degree.

      Conclusion

      Taken together, our data showed the potential advantage of sequencing ctDNA in SCLC over than that in NSCLC to reveal the global genomic landscape. SCLC ctDNA analysis will be used as a powerful research tool that can shed light on this poorly understood disease and could also provide clinical information that benefits patients.