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Y. Wang



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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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      P1.01-034 - Cerebrospinal Fluid and Plasma Tumor DNA Profiling Reveals Heterogeneity of CNS Metastasis in Patients with Non-Small-Cell Lung Cancer (ID 8937)

      09:30 - 09:30  |  Author(s): Y. Wang

      • Abstract

      Background:
      Tumor heterogeneity in central nervous system (CNS) metastases may lead to poor response to treatment in some patients with non-small-cell lung cancer (NSCLC), and genotyping of cell-free DNA (cfDNA) from cerebrospinal fluid is a promising method to reveal CNS metastasis specific gene alterations.

      Method:
      We conducted deep-sequencing on a 168-gene panel in cfDNA from matched cerebrospinal fluid (CSF) and plasma among 32 advanced or progressive NSCLC patients with indicated CNS metastases.

      Result:
      We detected single nucleotide variants (SNV) in 68.8% (22/32) of CSF samples and 77.4% (24/31) of plasma samples. The SNV detection rate was 100% in cytology positive CSF samples (11/11) or samples with cfDNA above 20ng (8/8), while it dropped to 53.3% (11/21) in cytology negative CSF samples and 58.3% (14/24) in samples with cfDNA below 20ng. Enriched copy number variations were detected in 10 patients. We also found CNS metastases specific driver gene alterations in 10 patients, including gene mutations (EGFR, TP53, RB1) or amplifications (MET, ERBB2). Among them, 3 patients carried common gene alterations with plasma. In two patients with only intracranial progression after targeted therapy or chemotherapy, driver gene mutations were detected in CSF samples but not in paired plasma.

      Conclusion:
      CSF profiling could successfully reflect genetic alterations for the CNS metastatic sites for both cytology positive or negative patients. Copy number amplifications and mutations on TP53 and RB1 are unique events identified in CSF. NGS on CSF and plasma ctDNA reveals tumor heterogeneity in NSCLC patients with CNS metastasis.