Assessing in house comprehensive genomic profiling by liquid biopsy for NSCLC patients
Andrea Vingiani, Alberta Piccolo, Adele Busico, Iolanda Capone, Elena Tamborini, Federica Perrone, Cinzia De Marco, Paolo Verderio, Chiara M. Ciniselli, Claudia Proto, Marta Brambilla, Giuseppe Lo Russo, Elena Conca, Andrea Devecchi, Daniele Lorenzini, Luca Agnelli, Giancarlo PruneriPurpose:
Liquid biopsy has emerged as a valuable tool for detecting therapeutic targets and resistance mechanisms. This study evaluated the analytical performance and clinical utility of TruSight Oncology 500 ctDNA (TSO500) compared to the FDA-approved Guardant360 CDx (G360) in detecting actionable alterations in non-small cell lung cancer (NSCLC) patients progressing on targeted therapies.
Patients and methods:
We analyzed 44 plasma samples from 36 consecutive metastatic NSCLC patients with known molecular drivers (
Results:
TSO500 demonstrated high sensitivity for G360-identified variants (81.02% overall; 85.26% for pathogenic/likely pathogenic variants). Concordance was particularly high for ESCAT I alterations (95.2% sensitivity), including 100% sensitivity for gene fusions (five detected fusions). TSO500 identified 102 additional variants not detected by G360. Among nine patients with concurrent tissue biopsy, TSO500 detected 16 potentially actionable mutations absent in tissue samples. Both assays identified resistance mutations in 12/26 patients (46.2%), with TSO500 detecting all but three G360-identified alterations. High correlation was observed between variant allele frequencies (Pearson's r = 0.89).
Conclusions:
TSO500 demonstrates high concordance with G360 for detecting actionable alterations and robust fusion identification. Its ability to detect additional variants and resistance mutations not found in tissue highlights its potential value in guiding personalized treatment decisions for NSCLC patients.