Enhanced Detection of Druggable Mutations in Non-Small Cell Lung Cancer Using Targeted Collection of Bronchial Washing Fluid Compared With Plasma and Tumor Tissue.

Abstract

Purpose: Next-generation sequencing (NGS) has become the gold standard for the molecular testing of patients with non-small cell lung cancer (NSCLC). This prospective study evaluated the performance of NGS using cell-free tumor DNA (ctDNA) extracted from bronchial washing fluid (BWF) collected via a targeted washing technique to detect druggable mutations.

Materials and methods: All study participants simultaneously underwent NGS using three sample types: (1) BWF, (2) plasma, and (3) tumor tissue collected during bronchoscopy. The full patient set (FPS) included all enrolled patients, whereas the analysis intent group (AIG) included patients who underwent successful NGS across all specimen types (BWF, plasma, and tissue).

Results: Sixty and 50 patients were included in the FPS and AIG groups, respectively. In FPS, the detection rate of druggable mutations in BWF using NGS was 65%, which was significantly higher than that of plasma (47%) and tissue samples (48%; P = .003 and P = .002, respectively). In the AIG, the concordance rate for detecting druggable mutations between BWF and tissue samples was 94%. In addition, the detection rate of co-occurring genetic alterations in BWF using NGS was significantly higher than that in plasma samples (92% v 64%, P = .001), whereas it was comparable with that in tissue samples (92% v 94%, P = 1.000). No significant adverse events occurred during the BWF collection.

Conclusion: NGS using ctDNA from BWF obtained through a targeted washing technique is a feasible and reliable method for genomic profiling of NSCLC, providing a promising approach for identifying druggable mutations.