{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:51:05Z","timestamp":1777009865496,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L248057"],"award-info":[{"award-number":["L248057"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Purpose<\/jats:title>\n This study aimed to assess the efficacy and safety of intensity\u2010modulated radiotherapy (IMRT) combined with regorafenib with or without immune checkpoint inhibitors (ICIs) as a second\u2010 or later\u2010line treatment for advanced hepatocellular carcinoma (HCC).<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus ICIs after failures of at least one line of systemic treatment in a single center from April 2018 to August 2022 were retrospectively reviewed. Progression\u2010free survival (PFS) was the primary endpoint, while overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Fifty patients were included, with 44 (88.0%) in BCLC stage C, 37 (74.0%) having portal vein tumor thrombosis (PVTT), and 12 (24.0%) with extrahepatic metastasis. Thirty\u2010eight patients received conventional fractionated RT (56.4Gy\/22\u201328f), while 12 received hyperfractionated RT (50Gy\/5\u201310f). Twenty\u2010six were treated concurrently with regorafenib and 24 sequentially. ICIs were applied in 34 patients. For the entire cohort, when measured from the start of RT initiation, the median PFS and OS were 10.9\u2009months and not reached. The corresponding 2\u2010year PFS and OS rates were 25.3% and 53.5%, respectively. When assessed from regorafenib initiation, the median PFS and OS were 5.9\u2009months and not reached, with 2\u2010year PFS and OS rates of 22.8% and 54.9%, respectively. For tumors in the RT field, the ORR was 74.0% (RECIST) and 92.0% (mRECIST). The most common grade 3 toxicities were hand\u2010foot syndrome (16.0%), thrombocytopenia (8.0%), dermatitis (8.0%), and transaminase elevation (6.0%).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n IMRT concurrently or sequentially combined with regorafenib with or without ICIs is an effective, well\u2010tolerated, and promising regimen as second\u2010line or further\u2010line treatment in patients with advanced HCC.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.71745","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:21:45Z","timestamp":1775884905000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Intensity\u2010Modulated Radiotherapy Combined With Regorafenib With or Without Immune Checkpoint Inhibitors as Second\u2010Line Treatment for Advanced Hepatocellular Carcinoma: A Real\u2010World Cohort Study From a Single Center"],"prefix":"10.1002","volume":"15","author":[{"given":"Lingxia","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yirui","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-405X","authenticated-orcid":false,"given":"Liming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-3345","authenticated-orcid":false,"given":"Feng","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Radiology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago Biachi","family":"de Castria","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center Tampa Florida USA"},{"name":"Morsani College of Medicine University of South Florida Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjaya K.","family":"Satapathy","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Medicine and Northwell Center for Liver Diseases & Transplantation Northwell Health Manhasset New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-8142","authenticated-orcid":false,"given":"Vishal G.","family":"Shelat","sequence":"additional","affiliation":[{"name":"Department of General Surgery Tan Tock Seng Hospital Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaffer R. S.","family":"Mok","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology Moffitt Cancer Center Tampa Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Perlmutter Cancer Center of NYU Langone Health, NYU Grossman School of Medicine New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shulian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Center\/National Clinical Research 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