Next-Generation-Sequencing with the Base-Position Error Rate (BPER) method on circulating DNA in lung cancer patients

Background: Circulating tumor DNA (ctDNA) PCR-based methods have been approved at diagnosis or recurrence as companion tests for anti-EGFR therapies in lung cancer. However, the value of ctDNA to monitor treatment efficacy requires further evaluation. Using a newly validated Next-Generation Sequencing (NGS) approach we tested the clinical utility of ctDNA monitoring.Methods and Findings: We conducted a prospective observational study of ctDNA in monitoring patients with newly diagnosed advanced non-small cell lung cancers (NSCLC). The primary objective was the prognostic value of baseline ctDNA detection on overall survival. In this study 124 patients were included and plasma samples were informative at baseline (n=105), at first evaluation (n=85) and at tumor progression (n=66). CtDNA was assessed by ultra-deep targeted NGS using a dedicated variant caller algorithm. Common mutations were validated with digital PCR. Findings: We showed that optimized targeted NGS is a powerful method for ctDNA detection in clinics. We demonstrated that ctDNA is a prognostic and an early monitoring marker of treatment efficacy in NSCLC patients.