Usefulness of Circulating Tumor DNA in Identifying Somatic Mutations and Tracking Tumor Evolution in Patients With Non-small Cell Lung Cancer

作者：Moom R. Roosan, Isa Mambetsariev, Rebecca Pharaon, Jeremy Fricke, Hatim Husain, Karen L. Reckamp, Marianna Koczywas, Erminia Massarelli, Andrea H. Bild, Ravi Salgia · 发表于：CHEST Journal · 年份：2021 · DOI：10.1016/j.chest.2021.04.016 · 被引用次数：45 · 研究领域：Cancer Genomics and Diagnostics、Lung Cancer Treatments and Mutations、Lung Cancer Diagnosis and Treatment

BACKGROUND: The usefulness of circulating tumor DNA (ctDNA) in detecting mutations and monitoring treatment response has not been well studied beyond a few actionable biomarkers in non-small cell lung cancer (NSCLC). RESEARCH QUESTION: How does the usefulness of ctDNA analysis compare with that of solid tumor biopsy analysis in patients with NSCLC? METHODS: We retrospectively evaluated 370 adult patients with NSCLC treated at the City of Hope between November 2015 and August 2019 to assess the usefulness of ctDNA in mutation identification, survival, concordance with matched tissue samples in 32 genes, and tumor evolution. RESULTS: A total of 1,688 somatic mutations were detected in 473 ctDNA samples from 370 patients with NSCLC. Of the 473 samples, 177 showed at least one actionable mutation with currently available Food and Drug Administration-approved NSCLC therapies. MET and CDK6 amplifications co-occurred with BRAF amplifications (false discovery rate [FDR], < 0.01), and gene-level mutations were mutually exclusive in KRAS and EGFR (FDR, 0.0009). Low cumulative percent ctDNA levels were associated with longer progression-free survival (hazard ratio [HR], 0.56; 95% CI, 0.37-0.85; P = .006). Overall survival was shorter in patients harboring BRAF mutations (HR, 2.35; 95% CI, 1.24-4.6; P = .009), PIK3CA mutations (HR, 2.77; 95% CI, 1.56-4.9; P < .001) and KRAS mutations (HR, 2.32; 95% CI, 1.30-4.1; P = .004). Gene-level concordance was 93.8%, whereas the positive concordanc...