{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T03:30:37Z","timestamp":1777865437736,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Circulating tumor DNA (ctDNA) provides a noninvasive method to clarify patients' genomic alterations. This study evaluated plasma\u2010derived ctDNA before second\u2010line osimertinib administration to explore the relationships between genomic alterations and clinical outcomes in patients with advanced non\u2010small\u2010cell lung cancer (NSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 64 advanced NSCLC patients with EGFR T790M receiving second\u2010line osimertinib. Targeted DNA sequencing was conducted on plasma samples, and both clinical and genomic characteristics were assessed for the correlation with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Female patients showed longer progression\u2010free survival (PFS) than male patients. Smokers exhibited shorter PFS and overall survival (OS) than nonsmokers. EGFR exon 19 deletion (E19Del) tended to have improved PFS compared with L858R. Plasma T790M abundance was not associated with the response to osimertinib, PFS, or OS. Patients with TP53 mutations experienced significantly worse PFS than wild\u2010type ones. A significant PFS reduction was observed in patients with a blood tumor mutational burden (bTMB)\u2009\u2265\u20098, compared to those with a bTMB \u27e8\u20098 mut.\/Mb. The EGFR driver mutation type (E19Del versus L858R) and TP53 mutation status were independent factors influencing PFS by multivariate survival analysis. Furthermore, the combination of EGFR driver type and TP53 mutation status improved the predictive performance for clinical outcomes, including objective response rate (ORR) and PFS, but not OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified potential molecular features via ctDNA sequencing that were correlated to clinical outcomes in EGFR T790M\u2010positive advanced NSCLC treated with second\u2010line osimertinib.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71319","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:11:00Z","timestamp":1762945860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma\u2010Based Genomic Features Influencing Outcomes of\n                    <scp>T790M<\/scp>\n                    \u2010Positive Non\u2013Small Cell Lung Cancer Receiving Osimertinib"],"prefix":"10.1002","volume":"14","author":[{"given":"Heng","family":"Liu","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junrong","family":"Yan","sequence":"additional","affiliation":[{"name":"Medical Department Nanjing Geneseeq Technology Inc.  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjun","family":"He","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-8116","authenticated-orcid":false,"given":"Rixu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411817"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.70.3223"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612674"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2246"},{"key":"e_1_2_10_7_1","first-page":"3100","article-title":"T790M Detection Rate After First\u2010Line Combination Therapy With Bevacizumab and EGFR\u2010TKIs in Advanced NSCLC (TERRA Study)","volume":"13","author":"Kuo C. 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