A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer.

Abstract

e21584 Background: Pleural effusion (PE) is commonly observed in advanced lung cancer. Researches have suggested molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples in the real world setting. Methods: 656 metastatic lung cancer patients with pleural effusion were enrolled in this study. Seven hundred and thirty-two samples, including 351 samples of PE supernatant, 224 plasma, 138 tissue, and 25 PE sediments from these patients were collected and subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related genes in a real world setting. The efficacy of pleural effusion in detecting actionable mutations and identifying resistant mechanisms of targeted therapy were analyzed by comparing different samples. Results: Among the 656 NSCLC patients, 413 were in M1a stage and 243 were in M1b/M1c stage, while 272 were newly diagnosed and 384 was previously treated. When comparing different groups of stage and therapeutic history, PE supernatant was preferred as the choice for those patients (46.6% - 48.2% vs 23.3%-34.8% of plasma vs 16.8%-21.2% of tissue and 0.96%-7.3% of PE sediment). While mutant allele frequency (MAFs) of plasma in patients of M1a stage was significantly lower than that of M1b/c stages, MAFs was similar for PE supernatant. EGFR, KRAS, MET, ALK, BRAF, ERBB2, ROS1, and RET actionable mutations were identified in 60, 12, 9, 7, 6, 3, 2, and 1 of the 118 PE supernatant samples at M1a stage taken before treatment. PE-supernatant demonstrated higher sensitivity than plasma of detecting actionable mutations in M1a disease (84.7% of PE-supernatant vs 42.1% of plasma, p < 0.01) but not in M1b/c stages (80.7% of PE-supernatant vs 86.4% of plasma). Seventy-two of the 117 patients who were resistant to 1st or 2nd generation of EGFR-TKI, 22 of the 42 patients resistant to osimertinib, and 9 of the 13 patients resistant to crizotinib had known resistant mutations identified. Remarkably, PE supernatant outperformed plasma in identifying resistant mutations to 1st/2nd generation EGFR-TKI (75.4% vs 29.8%, p < 0.001). Conclusions: This real world large cohort study verified that genomic profiling of PE-supernatant has higher actionable mutation detection sensitivity than plasma. It offers an alternative approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available.