Study on NGS-based molecular profiling of malignant pleural effusion supernatant cfDNA in guiding targeted therapy...

For patients with advanced non-small cell lung cancer (NSCLC), obtaining histological specimens can be challenging due to the presence of malignant pleural effusion (MPE), making liquid biopsy an important alternative for molecular profiling. This study aims to comparatively analyze the advantages of MPE supernatant over other sample types in molecular testing and to assess the feasibility and clinical utility of next-generation sequencing (NGS) using MPE supernatant for guiding targeted therapy.

A total of 77 NSCLC patients with MPE were enrolled from the Cancer Hospital, CAMS. Hybrid capture-based NGS was used to detect molecular alterations in supernatants and cell blocks derived from the same MPE sample. Mutation detection rates and their correlation with tumor cellularity were analyzed. Differences in molecular profiles between supernatant and matched plasma samples were assessed, and the predictive value of supernatant-derived epidermal growth factor receptor (EGFR) mutation status for targeted therapy response was evaluated.

MPE supernatants harbored a greater diversity of mutation types and exhibited slightly higher overall mutation detection rates compared to cell blocks (97.4% [75/77] vs. 89.6% [69/77]). As tumor cellularity decreased, mutation detection rates declined in supernatants and cell blocks; however, the reduction was less pronounced in supernatants. The mutation detection rate in supernatants was 96.0% (24/25), significantly higher than that in matched plasma (64.0% [16/25]), with a particularly notable difference in EGFR mutation detection rates (68.0% vs. 36.0%). Among 19 patients treated based on supernatant EGFR results, the median progression-free survival (PFS) was 9.0 months; EGFR-mutant patients achieved a median PFS of 10.5 months, compared to 2.0 months in wild-type patients (p = 0.17).

MPE supernatant is a highly effective sample source for molecular testing in NSCLC, demonstrating superior detection sensitivity compared to cell blocks-particularly at low tumor cellularity-and outperforming plasma in mutation detection. NGS results from supernatant provide reliable and clinically actionable data, enabling accurate guidance of targeted therapy for patients who cannot undergo tissue biopsy.