Cytological-negative pleural effusion can be an alternative liquid biopsy media for detection of EGFR mutation in NSCLC patients

Objective: Though the possibility of using malignant pleural effusions (MPEs) as alternatives for tumor tissues in epidermal growth factor receptor (EGFR) mutation test has been examined, the diagnosis of MPE is often clinically challenging, especially if the cytology is negative for malignancy. The aim of this study was to examine whether cytological-negative PE (CNPE) is useful in detecting EGFR mutation and evaluated its feasibility for predicting clinical outcomes. Method: In this study, we performed capture-based targeted sequencing using a panel consisting of 520 lung cancer-related genes to detect EGFR mutation status in 121 MPEs and 40 CNPE samples from 161 advanced lung adenocarcinoma patients. Patients underwent TKI treatment with gefitinib, icotinib or erlotinib if EGFR sensitizing mutations were detected at their tumor biopsies or pleural effusion sediment. Results: We revealed a mutation detection rate of 99.2% and 100% for MPE and CNPE, respectively (p = 1). The maximum allelic fraction (maxAF) of MPE and CNPE were 57.4% and 56.8%, respectively (p = 0.77). CNPE supernatant is comparable to MPE in reflecting the mutational profile of lung adenocarcinoma. EGFR activating mutations were detected in 47.5% (19/40) of CNPE supernatant sample and 32.5% (13/40) of matched tumor biopsies. CNPE sample is superior to tumor tissues in identifying EFGR mutation. Among the 72 EGFR-TKI treated patients, 51 were cytology positive and the remaining 21 were cytology negative. Our data showed that MPE patients exhibited comparable PFS (p = 0.41) and OS (p = 0.26) with CNPE patients treated with EGFR-TKI. Among the 21 CNPE patients received TKI treatment, patients harboring either L858R or exon 19 deletion had longer PFS than patients without a detectable mutation (p = 0.036). Conclusion: Collectively, we demonstrated that CNPE supernatant provided a comprehensive profile of NSCLC, and can serve as a reliable lipid biopsy media for EGFR mutational detection.