The diagnostic accuracy of next-generation sequencing in advanced NSCLC.

Background: Comprehensive genomic profiling is crucial for guiding treatment in advanced non-small cell lung cancer (NSCLC). However, tumor tissue-based targeted panel next-generation sequencing (TP-NGS) faces challenges, such as inadequate tissue sampling. Circulating tumor DNA (ctDNA) from peripheral blood has emerged as an alternative. Methods: Participants with advanced NSCLC were enrolled in a Precision Oncology Program to enhance personalized treatments. TP-NGS was conducted using FoundationOne®CDx and FoundationOne®Liquid CDx. The study included an unpaired cohort and a paired cohort. We evaluated the impact of ctDNA tumor fraction (TF) on TP-NGS diagnostic accuracy, focusing on sensitivity as a key metric of efficacy. Results: We prospectively analyzed data from 561 patients, of whom 62·4 % (n = 340) were in the unpaired cohort and 39·4 % (n = 221) were in the paired cohort. Specifically, in the paired cohort, actionable mutations were found in 50·2 % (n = 111) of patients, predominantly common Conclusion: In the context of high ctDNA TF, blood-based TP-NGS can detect clinically actionable mutations and may effectively replace tissue biopsies when obtaining tumor tissue is impractical.