Amplicon-based DNA and RNA unified NGS for enhanced fusion variant detection in suboptimal real-world NSCLC FFPE specimens

Abstract

Highlights • Unified DNA+RNA amplicon NGS delivered guideline-relevant biomarkers from 759 real-world NSCLC FFPE samples, including small biopsies and cytology.• High success rates (>95%) across all specimen types suggest that a single low-input assay can often replace sequential DNA→RNA testing and reduce repeat biopsies.• Robust performance in 5–8-year archived FFPE samples (≥96% success) enables treatment decisions even when only old tissue blocks are available.• D+R NGS confirmed 99.3% of known fusions/exon-skipping events and rescued additional actionable alterations that would otherwise be missed by standard workflows.• Detecting 18.2% more targetable fusions in DNA-NGS–negative cases has the potential to change first-line treatment selection from empirical chemo/chemo-immunotherapy to matched TKIs.