Assessing In House Comprehensive Genomic Profiling by Liquid Biopsy for NSCLC Patients

Liquid biopsy has emerged as a valuable tool for detecting therapeutic targets and resistance mechanisms. In this study, we aimed at evaluating the analytical performance of the TruSight Oncology 500 ctDNA (TSO500) compared to the FDA-approved Guardant360 CDx (G360) in detecting actionable alterations in NSCLC patients progressing on targeted therapies. We analysed 44 plasma samples from 36 consecutive metastatic NSCLC patients with known molecular drivers. The comparative analysis included 31 paired samples from 27 patients. TSO500 demonstrated high sensitivity in detecting G360-identified variants (81.02%). Concordance was particularly high for ESCAT I alterations (sensitivity: 95.2%), including gene fusions (100% sensitivity). Both LB assays identified resistance mutations in 12/26 patients, with TSO500 detecting all but 3 G360-identified resistance alterations. Our findings support TSO500's analytical validity and clinical utility, demonstrating high concordance with G360 for actionable alterations detection, highlighting its potential value in guiding treatment decisions.