{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:23:28Z","timestamp":1784172208840,"version":"3.55.0"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:sec id=\"ab-cbr220027-4\"><jats:title>Importance<\/jats:title><jats:p>Molecular testing in non\u2013small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr220027-5\"><jats:title>Objective<\/jats:title><jats:p>To prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing <jats:italic>EGFR<\/jats:italic> variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr220027-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant <jats:italic>EGFR<\/jats:italic> status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR <jats:italic>EGFR<\/jats:italic> testing. <jats:italic>EGFR<\/jats:italic> status results with ddPCR testing of PE-cfDNA and blood were compared with <jats:italic>EGFR<\/jats:italic> status in matched tumor biopsy or PE cell block samples.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr220027-7\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Specificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing <jats:italic>EGFR<\/jats:italic> variants and acquired T790M variation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr220027-8\"><jats:title>Results<\/jats:title><jats:p>Among 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38\/102) were <jats:italic>EGFR<\/jats:italic>-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (\u0138\u2009=\u20090.94, <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) for the detection of sensitizing <jats:italic>EGFR<\/jats:italic> variants. It was more sensitive than plasma in detecting sensitizing <jats:italic>EGFR<\/jats:italic> variants (97% vs 74%, <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001). In cohort 2, 38% (15 of 40) were positive for the <jats:italic>EGFR<\/jats:italic> T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (\u0138\u2009=\u20090.42, <jats:italic>P<\/jats:italic>\u2009=\u2009.004) for acquired T790M. The <jats:italic>EGFR<\/jats:italic> T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr220027-9\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this diagnostic study, <jats:italic>EGFR<\/jats:italic> variants could be accurately detected from PE-cfDNA in patients with NSCLC. More <jats:italic>EGFR<\/jats:italic> T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting <jats:italic>EGFR<\/jats:italic> variants in patients with advanced NSCLC.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.6109","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T16:32:16Z","timestamp":1672331536000},"page":"261","source":"Crossref","is-referenced-by-count":16,"title":["Testing for <i>EGFR<\/i> Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non\u2013Small Cell Lung Cancer"],"prefix":"10.1001","volume":"9","author":[{"given":"Kirsty W. C.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly S. C.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxia","family":"Gai","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yat Ming","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen K. C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar S. H.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Khoon","family":"Lee","sequence":"additional","affiliation":[{"name":"National Health and Medical Research Council (NHMRC) Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca M. W.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherwood Y. H.","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai F.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny N. P.","family":"Kam","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony S. K.","family":"Mok","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong"},{"name":"State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"cbr220027r1","doi-asserted-by":"publisher","first-page":"i3","DOI":"10.1093\/annonc\/mdx702","article-title":"Overview of current systemic management of EGFR-mutant NSCLC.","volume":"29","author":"Hsu","year":"2018","journal-title":"Ann Oncol"},{"issue":"7","key":"cbr220027r2","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer.","volume":"376","author":"Mok","year":"2017","journal-title":"N Engl J Med"},{"issue":"3","key":"cbr220027r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtocrr.2022.100290","article-title":"Clinical and 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