{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T19:16:58Z","timestamp":1787339818538,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102023R1A2C2004339"],"award-info":[{"award-number":["NRF\u20102023R1A2C2004339"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102023R1A2C2006375"],"award-info":[{"award-number":["NRF\u20102023R1A2C2006375"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u201000440714"],"award-info":[{"award-number":["RS\u20102024\u201000440714"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with advanced hepatocellular carcinoma (HCC). Here, we investigate the organ\u2010specific objective response rate (OSORR) of nivolumab plus ipilimumab (Nivo\/Ipi) combination treatment, considering prior ICI exposure, compared with nivolumab (Nivo) monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 204 lesions from Nivo\/Ipi\u2010treated and 305 lesions from Nivo\u2010treated patients with advanced HCC at five referral cancer centers in Korea. Organ\u2010specific response criteria were adopted from Response Evaluation Criteria in Solid Tumors 1.1, according to the indicated sites: the liver, lung, lymph nodes (LNs), and other metastatic sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nivo\/Ipi combination therapy showed OSORRs of 18.1% in the liver, 17.7% in the lungs, 30.0% in LNs, and 12.5% in other metastatic sites. Patients without prior ICI exposure had OSORRs of 29.0% in the liver, 31.3% in the lungs, 33.3% in LNs, and 23.1% in other metastatic sites (72 individual lesions). Conversely, patients with prior ICI exposure had OSORRs of 11.5% in the liver, 11.4% in the lung, 27.8% in LNs, and 7.4% in other metastatic sites (132 individual lesions). Furthermore, patients who achieved a response in the liver or the lung had longer progression\u2010free and overall survival, compared with those without responses. Nivo monotherapy yielded OSORRs of 13.5%, 25.3%, 39.3%, and 18.4% in the liver, lungs, LNs, and other metastatic sites, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Nivo\/Ipi combination therapy induced superior intrahepatic responses compared to Nivo monotherapy in patients with advanced HCC without prior ICI exposure, highlighting its potential to overcome liver\u2010specific immune tolerance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70997","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T10:34:51Z","timestamp":1749465291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Organ\u2010Specific Responses to Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma: A Multicenter, Retrospective Study"],"prefix":"10.1002","volume":"14","author":[{"given":"Jung Sun","family":"Kim","sequence":"first","affiliation":[{"name":"Medical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"},{"name":"CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngun","family":"Kim","sequence":"additional","affiliation":[{"name":"CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beodeul","family":"Kang","sequence":"additional","affiliation":[{"name":"Medical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Internal Medicine Haeundae Paik Hospital, Inje University College of Medicine  Busan Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ulsan University Hospital, University of Ulsan College of Medicine  Ulsan Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Suk","family":"Lee","sequence":"additional","affiliation":[{"name":"Medical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Yong","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Yeong","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Sang","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Gon","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine Yonsei University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-6453","authenticated-orcid":false,"given":"Sanghoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Radiology CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0484-6658","authenticated-orcid":false,"given":"Chansik","family":"An","sequence":"additional","affiliation":[{"name":"Department of Radiology CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-6155","authenticated-orcid":false,"given":"Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Oncology, Department of Internal Medicine CHA Bundang Medical Center, CHA University School of Medicine  Seongnam Korea"},{"name":"CHA University School of Medicine  Seongnam Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6979-5812","authenticated-orcid":false,"given":"Hong Jae","family":"Chon","sequence":"additional","affiliation":[{"name":"Medical Oncology, Department of Internal Medicine CHA 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