{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:00:11Z","timestamp":1790312411437,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the association of ctDNA-based molecular retesting with treatment timeliness and clinical outcomes in patients with advanced EGFR-mutant NSCLC after first-line EGFR-TKI resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed patients with advanced EGFR-mutant NSCLC who had radiologically confirmed progression after first-line EGFR-TKIs between 2019 and 2024. Patients were classified as no retesting (n=86), tissue NGS (n=94), or ctDNA testing (n=49). Primary endpoints were second-line progression-free survival (2L-PFS) and overall survival from initiation of second-line therapy (2L-OS). Secondary endpoints included time to treatment initiation (TTI) and treatment patterns. Survival was analyzed using Kaplan\u2013Meier and log-rank methods; Cox models were used for exploratory subgroup analyses. A 1:1:1 propensity score\u2013matched analysis and sensitivity analyses restricted to patients who initiated second-line therapy within 28 or 30 days after progression were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 229 patients, median TTI was shorter with ctDNA than tissue NGS (11.0 vs. 20.5 days, P &amp;lt; 0.001). Subsequent targeted therapy was most frequently used in the ctDNA group (95.9%), followed by the tissue NGS (89.4%) and no-retesting groups (81.4%; P = 0.039). After matching, median 2L-PFS was 5.0, 9.0, and 9.0 months in the no-retesting, tissue NGS, and ctDNA groups, respectively (overall P = 0.005). Median 2L-OS was 12.0, 20.0, and 19.0 months, respectively (overall P = 0.074). No significant differences in 2L-PFS or 2L-OS were observed between ctDNA and tissue NGS, and findings were consistent in 28- and 30-day sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with tissue NGS, ctDNA testing was associated with shorter TTI, with no significant differences in 2L-PFS or 2L-OS. The ctDNA group had the highest observed targeted therapy use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1969822","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:28:07Z","timestamp":1790310487000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of post-resistance molecular retesting strategies on treatment timeliness and clinical outcomes in EGFR-mutant advanced NSCLC: a real-world study"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenting","family":"Zhang","sequence":"first","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhe","family":"Xu","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Meng","sequence":"additional","affiliation":[{"name":"Fuzong Clinical Medical College of Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongquan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Fuzong Clinical Medical College of Fujian Medical University & The 900th Hospital of Joint Logistic Support Force, People\u2019s Liberation Army (PLA)","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1056\/NEJMoa1913662","article-title":"Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC","volume":"382","author":"Ramalingam","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0573-8","article-title":"Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer","volume":"121","author":"Leonetti","year":"2019","journal-title":"Br J Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1038\/s41467-023-35962-x","article-title":"Analysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial","volume":"14","author":"Chmielecki","year":"2023","journal-title":"Nat Commun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.12.009","article-title":"Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Hendriks","year":"2023","journal-title":"Ann Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.06.017","article-title":"Liquid biopsy for advanced NSCLC: A consensus statement from the International Association for the Study of Lung Cancer","volume":"16","author":"Rolfo","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.520","article-title":"ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group","volume":"33","author":"Pascual","year":"2022","journal-title":"Ann Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.76.8671","article-title":"Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review","volume":"36","author":"Merker","year":"2018","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.25332","article-title":"Association of circulating tumor DNA testing before tissue diagnosis with time to treatment among patients with suspected advanced lung cancer: The ACCELERATE nonrandomized clinical trial","volume":"6","author":"Garc\u00eda-Pardo","year":"2023","journal-title":"JAMA Netw Open"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.7","article-title":"Liquid biopsies come of age: towards implementation of circulating tumour DNA","volume":"17","author":"Wan","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B11","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12885-023-10674-z","article-title":"Plasma ctDNA increases tissue NGS-based detection of therapeutically targetable mutations in lung cancers","volume":"23","author":"Xie","year":"2023","journal-title":"BMC Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.02.003","article-title":"ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer","volume":"33","author":"Passaro","year":"2022","journal-title":"Ann Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-19-0624","article-title":"Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer","volume":"25","author":"Leighl","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An introduction to propensity score methods for reducing the effects of confounding in observational studies","volume":"46","author":"Austin","year":"2011","journal-title":"Multivariate Behav Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m4087","article-title":"Mortality due to cancer treatment delay: systematic review and meta-analysis","volume":"371","author":"Hanna","year":"2020","journal-title":"Bmj"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213209","article-title":"Time to initial cancer treatment in the United States and association with survival over time: An observational study","volume":"14","author":"Khorana","year":"2019","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol31100449","article-title":"Implementation of liquid biopsy in non-small-cell lung cancer: An Ontario perspective","volume":"31","author":"Breadner","year":"2024","journal-title":"Curr Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1186\/s12885-025-15227-0","article-title":"Implementing liquid biopsy NGS in stage III\/IV NSCLC: clinical utility assessment from a real-world Chinese cohort","volume":"25","author":"Yang","year":"2025","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41571-020-0423-x","article-title":"Strategies for the successful implementation of plasma-based NSCLC genotyping in clinical practice","volume":"18","author":"Aggarwal","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.4305","article-title":"Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer","volume":"5","author":"Aggarwal","year":"2019","journal-title":"JAMA Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.2311","article-title":"Regarding the congruence between 2 circulating tumor DNA sequencing assays","volume":"4","author":"Oxnard","year":"2018","journal-title":"JAMA Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-17-3831","article-title":"Validation of a plasma-based comprehensive cancer genotyping assay utilizing orthogonal tissue- and plasma-based methodologies","volume":"24","author":"Odegaard","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"224ra224","DOI":"10.1126\/scitranslmed.3007094","article-title":"Detection of circulating tumor DNA in early- and late-stage human Malignancies","volume":"6","author":"Bettegowda","year":"2014","journal-title":"Sci Transl Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp369","article-title":"Detecting an overall survival benefit that is derived from progression-free survival","volume":"101","author":"Broglio","year":"2009","journal-title":"J Natl Cancer Inst"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/jto.0000000000000548","article-title":"Multitrial evaluation of progression-free survival as a surrogate end point for overall survival in first-line extensive-stage small-cell lung cancer","volume":"10","author":"Foster","year":"2015","journal-title":"J Thorac Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s43441-026-00924-0","article-title":"Evaluating post-progression survival in the context of progression-free survival benefits: A revisit of the CodeBreaK200 design","volume":"60","author":"Wei","year":"2026","journal-title":"Ther Innov Regul Sci"},{"key":"B28","doi-asserted-by":"publisher","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"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.77.2293","article-title":"Patient-reported symptoms and impact of treatment with osimertinib versus chemotherapy in advanced non-small-cell lung cancer: The AURA3 trial","volume":"36","author":"Lee","year":"2018","journal-title":"J Clin Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-023-03286-3","article-title":"Expert consensus to optimize the management of older adult patients with advanced EGFR-mutated non-small cell lung cancer","volume":"25","author":"Nadal","year":"2023","journal-title":"Clin Transl Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1969822\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:28:08Z","timestamp":1790310488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1969822\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":30,"alternative-id":["10.3389\/fonc.2026.1969822"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1969822","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"article-number":"1969822"}}