{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:13Z","timestamp":1791262513472,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["82403096"],"award-info":[{"award-number":["82403096"]}],"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":["ZR2025LH162"],"award-info":[{"award-number":["ZR2025LH162"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS1427"],"award-info":[{"award-number":["ZR2025MS1427"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Liver metastasis represents one of the frequent drivers for cancer\u2010related mortality in lung adenocarcinoma. For advanced lung adenocarcinoma harboring wild\u2010type oncogene drivers, chemotherapies in combination with immune checkpoint inhibitors (ICIs) and\/or bevacizumab (named IC, BC, and IBC, respectively) are alternative first\u2010line schemes as recommended by canonical treatment guidelines. However, due to the immunosuppressive tumor microenvironment in the liver, patients with liver metastases are less effective to ICIs. For this subpopulation, the optimal regimen is still undetermined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective multicenter cohort study, treatment\u2010na\u00efve lung adenocarcinoma patients with wild\u2010type oncogene drivers and liver metastases were enrolled from 4 cancer centers between January 2018 and December 2023. All these patients received BC, IC, or IBC as the first\u2010line therapies. Propensity Score Matching (PSM) was applied to balance baseline covariates. Kaplan\u2010Meier survival analysis, log\u2010rank tests, and Cox proportional\u2010hazards regression were used to compare PFS and OS among groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 191 Patients were enrolled, in which 70 (36.6%) received IC treatment, 70 (36.6%) received BC and 51 (26.7%) received IBC treatment. After PSM, 135 eligible patients were selected, including 45 Patients in each group. IBC group showed a slightly higher ORR (44.4%) and significantly higher DCR (95.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013) compared with BC (ORR\u2009=\u200937.2%, DCR\u2009=\u200981.4%) and IC (ORR\u2009=\u200938.5%, DCR\u2009=\u200971.8%) groups, as evaluated by the primary lung lesions. When liver metastases were used as target lesions, similar response was observed. The median progression\u2010free survival (mPFS) in patients receiving IBC (8.48\u2009months, 95% CI: 5.98\u201316.10\u2009months) was significantly longer than those receiving BC (5.09\u2009months, 95% CI: 3.55\u20137.46\u2009months) and IC (4.86\u2009months, 95% CI: 3.06\u20137.82\u2009months) (IBC vs. BC: HR\u2009=\u20090.477, 95% CI: 0.295\u20130.772,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002; IBC vs. IC: HR\u2009=\u20090.479, 95% CI: 0.292\u20130.784,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). IBC also showed a numerically longer OS than IC (18.99\u2009months vs. 12.52\u2009months; HR\u2009=\u20090.692, 95% CI: 0.429\u20131.114,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.128), although this difference did not reach statistical significance. Subgroup analyses, conducted as pre\u2010specified exploratory analyses, showed that patients with male gender, smoking history, brain metastasis, polymetastases and low PD\u2010L1 expression (&lt;\u200950%) displayed superior PFS when treated with IBC compared with their counterparts. Besides, IBC showed comparable adverse events relative to IC and BC treatments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IBC treatment showed superior efficacy in oncogene wild\u2010type lung adenocarcinoma patients with liver metastases, especially in those with male gender, smoking history, brain metastasis, polymetastases, and low PD\u2010L1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72282","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:33:07Z","timestamp":1791261187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of First\u2010Line Treatment Options for Oncogene Wild\u2010Type Lung Adenocarcinoma With Liver Metastases"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6999-4371","authenticated-orcid":false,"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"School of Clinical Medicine Shandong Second Medical University  Weifang China"},{"name":"Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihui","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Thoracic Radiation Oncology, Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-2727","authenticated-orcid":false,"given":"Qiaohong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Central Hospital Affiliated to Shandong First Medical University  Jinan Shandong P.R. 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