{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:00:27Z","timestamp":1785387627174,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The optimal sequencing of brain\u2010directed radiation and systemic therapy in stage IV non\u2013small cell lung cancer (NSCLC) with brain metastases remains uncertain in the era of CNS\u2010active systemic agents. We evaluated survival outcomes using national real\u2010world data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of adults diagnosed between 2010 and 2022 with stage IV NSCLC and brain metastases in the National Cancer Database who received both brain\u2010directed radiation and systemic therapy. Treatment sequence was classified as radiation\u2010first or systemic\u2010first based on initiation dates. Multivariable Cox proportional hazards models, stratified by treatment era (pre\u20102015 vs. 2015+), assessed associations with overall survival (OS), adjusting for demographic, clinical, tumor, and treatment factors. Propensity score matching and delayed\u2010entry sensitivity analyses were performed to address confounding and immortal time bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 45\u2009577 patients, 78.3% received radiation\u2010first and 21.7% received systemic therapy first. Unadjusted Kaplan\u2013Meier analysis showed no significant difference in OS (log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.624). In multivariable analysis, systemic\u2010first sequencing was associated with a modest increase in mortality (adjusted hazard ratio [aHR] 1.06; 95% CI: 1.04\u20131.09), which was consistent in propensity\u2010matched (HR 1.07; 95% CI: 1.04\u20131.11) and delayed\u2010entry analyses (aHR 1.09; 95% CI: 1.07\u20131.12). The use of systemic\u2010first therapy increased over time. Established prognostic factors demonstrated larger effect sizes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Systemic\u2010first sequencing was associated with a modest increase in adjusted mortality; however, the effect size was small relative to established prognostic factors and likely influenced by residual confounding and selection bias. These findings support individualized, multidisciplinary treatment decisions rather than a uniform sequencing strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70359","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:09:53Z","timestamp":1784506193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Treatment Sequencing and Overall Survival in Stage\n                    <scp>IV NSCLC<\/scp>\n                    With Brain Metastases: A National Cancer Database Study"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-0149","authenticated-orcid":false,"given":"Anand","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Medicine Rutgers New Jersey Medical  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7008-0214","authenticated-orcid":false,"given":"Pranav","family":"Gwalani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1485-5389","authenticated-orcid":false,"given":"Merry","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Medicine Rutgers New Jersey Medical  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-9204","authenticated-orcid":false,"given":"Ritik","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Medicine Rutgers New Jersey Medical  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6732-5956","authenticated-orcid":false,"given":"Joshua","family":"Kra","sequence":"additional","affiliation":[{"name":"Department of Medicine Rutgers New Jersey Medical  Newark New Jersey USA"},{"name":"Division of Hematology\/Oncology, Department of Medicine Rutgers New Jersey Medical School  Newark New Jersey USA"},{"name":"Rutgers Cancer Institute  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11912\u2010011\u20100203\u2010Y\/TABLES\/1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/CNCR.10541"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11060\u2010009\u20100060\u20109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.LUNGCAN.2004.07.967"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJCA.2020.03.006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/TLCR.2016.11.01"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1612674;SUBPAGE:STRING:FULL"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMOA1704795;JOURNAL:JOURNAL:NEJMS"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30111\u2010X"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2016.9839"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759\u20107714.14423;WGROUP:STRING:PUBLICATION"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13014\u2010015\u20100421\u20109"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02314;WGROUP:STRING:PUBLICATION"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02561"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JTHO.2026.01.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2026.44.16_SUPPL.8624"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.69.7144"},{"key":"e_1_2_9_19_1","unstructured":"\u201cNational Cancer Database (NCDB)|ACS \u201daccessed: January 31 2026. [Online]. Available https:\/\/www.facs.org\/quality\u2010programs\/cancer\u2010programs\/national\u2010cancer\u2010database\/."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMAONCOL.2016.6905"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0895\u20104356(92)90133\u20108"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ADVS.202502626;SUBPAGE:STRING:FULL"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S184922"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/NOAJNL\/VDAB106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JOP.19.00357"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/MCO.2025.2891"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00066\u2010024\u201002360\u20101"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/COC.0000000000000188"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/S11060\u2010021\u201003712\u2010Y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201015\u20100036"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.21.00485"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.15430\/JCP.2022.27.2.89"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/S40615\u2010023\u201001625\u20102"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70359","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.70359","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70359","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:36:38Z","timestamp":1785386198000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.70359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":32,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/1759-7714.70359"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.70359","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70359"}}