{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T16:59:59Z","timestamp":1785085199352,"version":"3.55.0"},"reference-count":39,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["82272753"],"award-info":[{"award-number":["82272753"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Noncommunicable Chronic DiseasesNational Science and Technology Major Project","award":["2023ZD0501600"],"award-info":[{"award-number":["2023ZD0501600"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>First-line immunotherapy-based combinations have improved outcomes in advanced hepatocellular carcinoma (HCC), but many patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC with portal vein tumor thrombus (PVTT) and\/or extrahepatic oligometastases remain difficult to treat and often unresectable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To characterize the safety, feasibility, and efficacy of a sequential strategy combining hepatic artery infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO), iparomlimab\/tuvonralimab plus bevacizumab, followed by stereotactic body radiotherapy (SBRT), in patients with BCLC stage C HCC with PVTT and\/or extrahepatic oligometastases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>The BITS-TO-HCC study is a prospective, single-center, single-arm, phase II trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis:<\/jats:title>\n                    <jats:p>Patients with BCLC stage C HCC complicated by PVTT and\/or extrahepatic oligometastases and Child\u2013Pugh class A liver function will be enrolled. On day 1 of each cycle, patients will receive HAIC-FO followed by bevacizumab plus iparomlimab\/tuvonralimab after protocol-defined laboratory reassessment. HAIC-FO will be delivered for up to four cycles. After cycle 4, patients without progressive disease will receive protocol-specified SBRT (25\u201340\u2009Gy in 5 fractions). Patients with radiographic complete response or no residual SBRT-amenable lesion will continue systemic therapy and follow-up. The primary endpoint is progression-free survival. Secondary endpoints include objective response rate, disease control rate, overall survival, local control rate, safety, and quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics:<\/jats:title>\n                    <jats:p>The final protocol was approved by the Ethics Committee of the Affiliated Cancer Hospital of Shandong First Medical University.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>This trial will prospectively evaluate whether a sequential strategy combining HAIC with bevacizumab plus iparomlimab\/tuvonralimab followed by SBRT can provide a surgery-sparing, ablative locoregional\u2013systemic pathway for this high-risk population, potentially enhancing efficacy while maintaining an acceptable safety profile.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic toggle=\"yes\">Trial registration<\/jats:italic>\n                        :\n                      <\/jats:bold>\n                      This study is registered on ClinicalTrials.gov Identifier: NCT07062055 (July 14, 2025).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359261470693","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:00:41Z","timestamp":1784887241000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bevacizumab plus iparomlimab\/tuvonralimab with hepatic artery infusion chemotherapy followed by stereotactic body radiotherapy in patients with BCLC stage C hepatocellular carcinoma with thrombus and\/or extrahepatic oligometastases (BITS-TO-HCC): study protocol of a prospective, single-center, single-arm, phase II study"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-6019","authenticated-orcid":false,"given":"Yuxin","family":"Liu","sequence":"first","affiliation":[{"name":"Shandong University Cancer Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"},{"name":"Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China"},{"name":"Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 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