{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:33:41Z","timestamp":1786696421903,"version":"build-2736575974"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Grant No.82272752"],"award-info":[{"award-number":["Grant No.82272752"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"natural science foundation of shandong province","doi-asserted-by":"publisher","award":["ZR2023LZY007"],"award-info":[{"award-number":["ZR2023LZY007"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Province Key Discipline of Traditional Chinese Medicine Construction Project","award":["2022 No.04"],"award-info":[{"award-number":["2022 No.04"]}]},{"name":"National Key Laboratory for the Integration and Innovation of Classical Formulas and Modern Chinese Medicine"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The optimal approach to treatment intensification for epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma with brain metastases remains a topic of debate, especially in the context of high-risk molecular features such as TP53 co-mutation. The extent to which baseline clinical risk influences treatment efficacy is yet to be determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We aim to systematically evaluate the prognostic significance of EGFR\/TP53 co-mutations in treatment-na\u00efve patients with lung adenocarcinoma and newly diagnosed brain metastases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>This study enrolled 218 treatment-na\u00efve patients with EGFR-mutant lung adenocarcinoma and brain metastases who received first-line third-generation EGFR-tyrosine kinase inhibitors (TKIs). Treatment effects were evaluated using interaction models stratified by Lung-molGPA scores. Stratification: Group A (Lung-molGPA 1\u20132) versus Group B (Lung-molGPA 2.5\u20134).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Within each group, the influence of TP53 co-mutations on survival was analyzed. Additionally, among patients with TP53 co-mutations, the effects of cranial radiotherapy (CRT) and treatment with either third-generation EGFR-TKIs monotherapy or third-generation EGFR-TKIs combined with chemotherapy on overall survival (OS) were further investigated, taking into account the Lung-molGPA scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The Lung-molGPA significantly influenced the prognostic impact of TP53 mutations and the survival benefits of treatment intensification strategies (log-rank test\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.044, hazard ratio (HR)\u2009=\u20092.1832, 95% confidence interval (CI): 1.023\u20134.661). In patients with low Lung-molGPA scores, intensification with CRT did not correlate with a survival advantage (32.2 vs 28.0\u2009m, log-rank test\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.5088, HR\u2009=\u20091.417, 95% CI: 0.4768\u20134.211). Conversely, in patients with high Lung-molGPA scores, both CRT and systemic intensification were associated with improved outcomes (44.0 vs 26.3\u2009m, log-rank test\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0054, HR\u2009=\u20090.3199, 95% CI: 0.1585\u20130.6456; 20.1 vs 32.3\u2009m, log-rank test\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0074, HR\u2009=\u20092.547, 95% CI: 1.113\u20135.831).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Baseline clinical risk, as delineated by the Lung-molGPA, serves as a crucial determinant of therapeutic benefit in cases of EGFR-mutant lung adenocarcinoma with cerebral metastases. Implementing risk-adapted treatment intensification strategies could potentially prevent overtreatment in patients classified as low-risk, while simultaneously optimizing clinical outcomes in high-risk cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261471117","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:53:49Z","timestamp":1786517629000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lung-molGPA may stratify the prognostic impact of TP53 co-mutation in EGFR-mutant lung adenocarcinoma with brain metastases: a multi-center retrospective analysis"],"prefix":"10.1177","volume":"18","author":[{"given":"Guangchuan","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Nan\u2019an District, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Nan\u2019an District, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fan","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, China"},{"name":"Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Yuanzhu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenran","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, China"},{"name":"Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamao","family":"Lin","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, China"},{"name":"Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan City, Shandong Province, 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