{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:31:53Z","timestamp":1777401113455,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008746","name":"National Cancer Center","doi-asserted-by":"publisher","award":["2210551\u20101"],"award-info":[{"award-number":["2210551\u20101"]}],"id":[{"id":"10.13039\/100008746","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patterns of treatment failure and subsequent treatment in non\u2010small cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)\u2010tyrosine\u2010kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records. Patients' tumor characteristics, efficacy outcomes, affected organs from radiology studies, and treatment modalities before and after osimertinib were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighty\u2010four patients were included. At osimertinib initiation, bone (50.0%) and brain (41.9%) were the commonest single metastatic sites, whereas thoracic involvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo\u2010progressive disease (PD) and central nervous system (CNS)\u2010sanctuary PD were observed in 15 (17.9%) and 3 (3.6%) patients, respectively. Most patients without brain metastasis (BM) at osimertinib initiation remained BM\u2010free (46\/49, 93.9%), and 60% of patients (21\/35) with pre\u2010existing BM showed intracranial disease control despite extracranial PD. The resistance mechanisms to osimertinib were explored in 23 patients (27.4%), and T790M\u2010loss was observed in 14 patients (60.9%) who had worse survival outcomes than those without T790M\u2010loss (progression\u2010free survival, 5.4 vs. 16.5\u2009months, <jats:italic>p<\/jats:italic>\u2009=\u20090.02; overall survival, not reached, <jats:italic>p<\/jats:italic>\u2009=\u20090.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PD during osimertinib treatment occurred preferentially in the thorax and pre\u2010existing sites. Extracranial PD prevailed over intracranial PD regardless of baseline BM and prior brain radiation. These results support osimertinib's intracranial efficacy and may guide treatment strategies for <jats:italic>EGFR\u2010<\/jats:italic>mutated NSCLC with BM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5926","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T10:25:31Z","timestamp":1682418331000},"page":"12285-12298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dynamics of disease progression during treatment with Osimertinib in patients with <i>EGFR<\/i> T790M\u2010positive non\u2010small cell lung cancer"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-8335","authenticated-orcid":false,"given":"Hye Sook","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Oncology\/Hematology, Department of Internal Medicine Ilsan Paik Hospital, Inje University  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun Young","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Radiology and Research Institute and Hospital National Cancer Center  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo\u2010Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology and Research Institute and Hospital National Cancer Center  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyae Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology and Research Institute and Hospital National Cancer Center  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngjoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Lung Cancer, Research Institute and Hospital National Cancer Center  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u2010Youn","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Lung Cancer, Research Institute and Hospital National Cancer Center  Goyang Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.4235"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30508-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2013.11.008"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24877"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2015.01.020"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612674"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713137"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2012.09.016"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.2017.026500"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyp167"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2011.44"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30532-0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.2217\/lmt-2016-0012"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31891"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2018.11.037"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30480-0"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S287466"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.02.020"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.12.042"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2019.06.2428"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-019-00644-6"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2017.03.010"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2018.03.106"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000648"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.02.020"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.02.014"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-019-02193-w"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1542"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.2969"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210225"}],"container-title":["Cancer 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