{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:15:50Z","timestamp":1771334150372,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011892","name":"Kaohsiung Chang Gung Memorial Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a major cause of cancer\u2010related mortality, particularly in patients with advanced stage. Atezolizumab plus bevacizumab (Ate\/Bev) is the standard first\u2010line therapy; however, its efficacy may be further enhanced using combination strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study evaluated the clinical impact of proton beam therapy (PBT) with Ate\/Bev in patients with unresectable HCC (uHCC). We retrospectively evaluated 362 patients with uHCC treated with Ate\/Bev between November 2020 and June 2023 at two centers in Taiwan. The patients were divided into the Ate\/Bev\u2010PBT and Ate\/Bev groups based on whether they received first\u2010line Ate\/Bev combined with PBT or Ate\/Bev alone. Propensity score matching was performed at a 1:2 ratio to reduce selection bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There were 39 and 71 patients in the Ate\/Bev\u2010PBT and Ate\/Bev groups, respectively. Treatment\u2010related adverse events were comparable between the two groups and were manageable, primarily involving mild\u2010to\u2010moderate liver inflammation. Compared with the Ate\/Bev group, the Ate\/Bev\u2010PBT group demonstrated significantly better objective response rates (56.8% vs 17.3%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), disease control rates (75.7% vs 44.2%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), progression\u2010free survival (7.3 vs 2.3\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and overall survival (16.7 vs 7.1\u2009months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02). In the multivariate analysis, Ate\/Bev\u2010PBT was strongly associated with reduced mortality (hazard ratio [HR], 0.406; 95% confidence interval [CI]: 0.236\u20130.700,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) after adjusting for preserved liver function, prognostic nutritional index and receiving sequential therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The addition of PBT to Ate\/Bev was associated with improved treatment response and survival in patients with uHCC without compromising safety of the treatment. This combined approach may represent a promising therapeutic strategy that warrants prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70465","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T11:50:56Z","timestamp":1764676256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proton Beam Therapy Boosts Outcomes of Atezolizumab\/Bevacizumab in Advanced Hepatocellular Carcinoma: A Propensity Score Analysis"],"prefix":"10.1111","volume":"46","author":[{"given":"Yuan\u2010Hung","family":"Kuo","sequence":"first","affiliation":[{"name":"Division of Hepatology\u2010Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital, Kaohsiung Medical Center  Kaohsiung Taiwan"},{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Teng","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen\u2010Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine Chang Gung Memorial Hospital, Kaohsiung Medical Center  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung\u2010Wei","family":"Su","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric Yi\u2010Liang","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Radiation Oncology and Proton Therapy Center Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing\u2010Shen","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Radiation Oncology and Proton Therapy Center Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung\u2010Han","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of General Surgery Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-0394","authenticated-orcid":false,"given":"Jen\u2010Yu","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Radiation Oncology and Proton Therapy Center Chang Gung Memorial Hospital, Kaohsiung Medical Center  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Chung","family":"Hsieh","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Chang Gung University  Taoyuan Taiwan"},{"name":"Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-9519","authenticated-orcid":false,"given":"Chao\u2010Hung","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Hepatology\u2010Gastroenterology, Department of Internal Medicine Chang Gung Memorial Hospital, Kaohsiung Medical Center  Kaohsiung Taiwan"},{"name":"College of Medicine, Chang Gung University  Taoyuan 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