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However, the efficacy and safety of integrating local\u2013regional therapy with chemotherapy, ICIs, and lenvatinib in advanced intrahepatic cholangiocarcinoma (ICC) remain unclear. This study evaluated the efficacy and safety of first-line treatment combining local\u2013regional therapy, chemotherapy, ICIs, and lenvatinib in advanced ICC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter study included 47 advanced ICC patients receiving local\u2013regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus chemotherapy, ICIs, and lenvatinib from October 2019 to January 2025. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and prognostic factors analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The multimodal therapy demonstrated mPFS of 10.2 months and mOS of 20.2 months. ORR and DCR reached 61.7% and 93.6%, respectively. Conversion surgery was performed in 10.6% (5\/47) of patients, with 60.0% (3\/5) achieving sustained remission. All patients experienced AEs, with grade 3\u20134 AEs in 66.0%, primarily including myelosuppression (23.4%), AST or ALT increased (19.1%), fatigue (14.9%), and pain (10.6%). No grade 5 AEs were observed, and all toxicities were manageable. Survival outcomes, tumor response rates, and grade 3\u20134 AE incidence showed no significant differences among local\u2013regional therapy subgroups. Multivariate analyses identified impaired performance status as an independent predictor of poorer OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combined regimen of local\u2013regional therapy, chemotherapy, ICIs, and lenvatinib exhibited marked efficacy and a tolerable safety profile, establishing it as a viable first-line approach for advanced ICC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00262-025-04085-1","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T07:55:55Z","timestamp":1748591755000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and safety of local\u2013regional therapy combined with chemotherapy, immune checkpoint inhibitors and lenvatinib as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study"],"prefix":"10.1007","volume":"74","author":[{"given":"Shuofeng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjian","family":"Piao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Xun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiongyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"issue":"1","key":"4085_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","volume":"7","author":"PJ Brindley","year":"2021","unstructured":"Brindley PJ, Bachini M, Ilyas SI, Khan SA, Loukas A, Sirica AE et al (2021) Cholangiocarcinoma. 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