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Malignant pleural effusions are common in non–small cell lung cancer (NSCLC). Molecular testing is among the most critical steps in the management of patients with advanced NSCLC. However, the optimal approach for epidermal growth factor receptor (EGFR) mutation testing in such effusion samples remains unclear.    Methods  We prospectively collected effusion samples from patients with EGFR–mutant NSCLC. Following sample centrifugation, genomic DNA and cell–free DNA were respectively extracted from the sediment and supernatants. EGFR mutation was detected through a real–time PCR assay.    Results  A total of 108 effusions from 78 patients were examined, with 12 and 96 obtained before and after EGFR tyrosine kinase inhibitor treatment, respectively. Carcinoma cells or atypical cells were identified in 73 effusions (67.6%). EGFR mutations were detected in 86 (79.6%) sediment and 84 (77.8%) supernatant samples. Among the effusions with positive cytological findings, the EGFR mutation detection rates were 95.9% (70/73) and 86.3% (63/73) in the sediment and supernatants, respectively. Among the effusions with negative cytological findings, the corresponding detection rates were 45.7% (16/35) and 60% (21/35), respectively. Current clinical practice is to arrange EGFR mutation testing only for sediment from cytologically positive effusions. Through the proposed cytology–based specimen triage, wherein sediment and supernatants with positive and negative cytological findings, respectively, are tested, the detection rate was increased from 64.8% (70/108) to 84.3% (91/108). At half of the cost, this strategy provided a detection rate only slightly lower than the rate in a combined test of all the sediment and supernatants (87.0%, 94/108).    Conclusions  The separate extraction of DNA from sediment and supernatants obtained from centrifuged effusion samples can improve the overall EGFR mutation detection rate. The present cytology–based specimen triage is an efficient strategy for EGFR mutation testing in patients with EGFR–mutant NSCLC.

Cytology–Based Specimen Triage for Epidermal Growth Factor Receptor Mutation Testing of Malignant Pleural Effusions in Non–Small Cell Lung Cancer