{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:06:19Z","timestamp":1789455979479,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303523"],"award-info":[{"award-number":["82303523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Leptomeningeal metastasis (LM) is a devastating complication of lung cancer. We investigated the clinical and molecular evolution of LM in the modern targeted\u2010therapy era and factors associated with post\u2010LM survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analyzed 201 patients with cytologically confirmed lung cancer LM diagnosed between November 2012 and May 2026. Patients were classified by LM diagnosis date (2012\u20132016 vs. 2017\u20132026). Intervals from lung cancer and Stage IV diagnosis to LM were compared using the Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      test. Paired primary tumor and cerebrospinal fluid (CSF) molecular profiles were assessed in 80 patients. Overall survival (OS) was evaluated using Kaplan\u2013Meier and prespecified multivariable cox analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Adenocarcinoma accounted for 93.0% of cases. The intervals from lung cancer and Stage IV diagnosis to LM were longer in the later cohort (23.7 vs. 13.8\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; 17.4 vs. 10.4\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Unadjusted OS from LM diagnosis did not differ significantly between eras (9.8 vs. 11.3\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.864). Tissue\u2010CSF driver discordance occurred in 7\/80 patients (8.75%). In multivariable analysis, later diagnostic era, smoking, and ECOG PS \u2265\u20092 were associated with higher mortality (adjusted HR, 1.826,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014; 1.847,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014; and 1.674,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007, respectively), whereas post\u2010LM third\u2010generation EGFR\u2010TKI exposure was associated with lower mortality (adjusted HR, 0.385;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The later era was associated with a longer interval to LM diagnosis but no statistically significant improvement in unadjusted post\u2010LM OS. Adjusted associations require cautious interpretation because of residual confounding and post\u2010baseline treatment bias. CSF profiling may provide clinically relevant information beyond primary tumor genotyping.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.70386","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:27:48Z","timestamp":1788164868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delayed Occurrence of Lung Cancer Leptomeningeal Metastasis and Era\u2010Associated Post\u2010\n                    <scp>LM<\/scp>\n                    Survival: A 14\u2010Year Single\u2010Center Cohort Study"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4334-587X","authenticated-orcid":false,"given":"Xiaoxing","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyue","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of International Medical Service Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0791-3673","authenticated-orcid":false,"given":"Chen","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Health Policy and Health Economics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5058-5658","authenticated-orcid":false,"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4040-6115","authenticated-orcid":false,"given":"Minjiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3540-2280","authenticated-orcid":false,"given":"Hanping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-3045","authenticated-orcid":false,"given":"Xiaoyan","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2832-2664","authenticated-orcid":false,"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9226-5393","authenticated-orcid":false,"given":"Mengzhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine Peking Union Medical College Hospital, Peking Union Medical College &amp; Chinese Academy of Medical Science  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70443-4"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy009"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-025-14583-1"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx221"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.09.140"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2026.108918"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70034-6"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-021-04763-w"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2022.11.050"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-24-477"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04396-1"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2023.101637"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.101594"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.06.001"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.70386","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:11:47Z","timestamp":1789452707000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.70386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":14,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/1759-7714.70386"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.70386","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70386"}}