The Diagnostic Accuracy of Next-Generation Sequencing in Advanced NSCLC

Abstract

<h3>Background</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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 <em>EGFR</em> mutations in 65·8% (n=73). The ctDNA TF high (TF>1%, range 1%-72%) group had a 100% positive percent agreement (PPA), while the ctDNA TF low group had a PPA of 47·5% for actionable mutations. The correlation between bTMB and tTMB was 0·13 for ctDNA TF low versus 0·71 for ctDNA TF high. The PPA for bTMB was 31·3% for ctDNA TF low and 92·3% for ctDNA TF high, with negative percent agreement (NPA) at 100% and 85·6%, respectively.</p><h3>Conclusion</h3><p>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.</p>