{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:44:58Z","timestamp":1789652698003,"version":"4.0.0"},"reference-count":7,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Objectives:<\/i><\/b> During targeted therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms. Sequential profiling of plasma cell-free DNA (cfDNA) provides a noninvasive method for early detection of patient progression. We investigated whether the genetic dynamics detected in cfDNA during treatment can act as a predictive or prognostic marker of outcome. <b><i>Methods:<\/i><\/b> Patients with advanced <i>EGFR<\/i>-mutated non-small cell lung cancer (NSCLC) were included for consecutive blood sampling during EGFR-tyrosine kinase inhibitor (TKI) treatment. Blood samples were serially collected from patients at baseline, first follow-up, and progression. Extracted cfDNA was analyzed with next-generation sequencing. <b><i>Results:<\/i><\/b> Serial plasma samples (<i>n<\/i> = 187) from 63 patients were analyzed, and 44 patients showed circulating tumor DNA (ctDNA). <i>EGFR<\/i> mutations were detected in 36 of the 44 patients at baseline (81.8%). <i>EGFR<\/i> mutations were no longer detected in 19 of 36 shedders (52.8%) at 2 months after EGFR-TKI treatment and rebounded with resistant <i>EGFR<\/i> mutations (T790M or C797S) at progression. Other driver mutations such as <i>KRAS<\/i> G12D and <i>BRAF<\/i> V600E were found at baseline regardless of tissue <i>EGFR<\/i> status, suggesting tumor heterogeneity. Detection of ctDNA (shedder) at baseline associated with poor overall survival (<i>p<\/i> = 0.04) compared to nonshedder. Furthermore, in patients showing <i>EGFR<\/i> mutations in plasma at baseline, the clearing rate of those during the first 8 weeks of treatment served as a positive predictor for clinical outcome. <b><i>Conclusion:<\/i><\/b> Longitudinal liquid biopsies capture spatial and temporal heterogeneity underlining resistance to EGFR-TKIs in NSCLC. Thus, ctDNA monitoring during EGFR-TKI treatment is useful for detecting resistance mutations or predicting response. Dense serial monitoring using blood enables early prediction of treatment failure and provides a window of opportunity for well-timed intervention. <\/jats:p>","DOI":"10.1159\/000516813","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T22:00:41Z","timestamp":1645653641000},"page":"228-237","source":"Crossref","is-referenced-by-count":10,"title":["Role of Circulating Tumor DNA Profiling in Patients with Non-Small Cell Lung Cancer Treated with EGFR Inhibitor"],"prefix":"10.1159","volume":"100","author":[{"given":"Bo Mi","family":"Ku","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghyun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Hoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seok","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunchil","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung-Ju","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Mu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.05.022"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.018"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0736"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3747\/co.25.3761"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.166"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.12.016"}],"container-title":["Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/516813","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/516813","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T14:59:02Z","timestamp":1745420342000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000516813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":7,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4,1]]},"published-print":{"date-parts":[[2022,4,5]]}},"URL":"https:\/\/doi.org\/10.1159\/000516813","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.19221222","asserted-by":"subject"}]},"ISSN":["0030-2414","1423-0232"],"issn-type":[{"value":"0030-2414","type":"print"},{"value":"1423-0232","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}