{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:04:21Z","timestamp":1789992261060,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002456","name":"Chonnam National University","doi-asserted-by":"publisher","award":["2025-0358-03"],"award-info":[{"award-number":["2025-0358-03"]}],"id":[{"id":"10.13039\/501100002456","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025-0358-03"],"award-info":[{"award-number":["2025-0358-03"]}],"id":[{"id":"https:\/\/ror.org\/05kzjxq56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Real-world data in high-risk patients remain limited; this study evaluated survival, safety, and prognostic factors in this patient group. Methods: This multicenter study retrospectively reviewed 783 patients who received Ate\/Bev from 2022\u20132024 across South Korea. High-risk patients (n = 252, 32.2%) were defined by main portal vein tumor thrombus (Vp4), tumor occupancy \u226550% of liver volume, or bile duct invasion. Propensity score matching (PSM) was performed to balance host-related factors between the high-risk and non-high-risk (n = 531) groups. Results: After PSM (251 pairs, n = 502), overall survival (median 10.4 vs. 14.9 months; HR 1.57, 95% CI 1.28\u20131.92, p &lt; 0.001) and progression-free survival (median 6.0 vs. 6.8 months; HR 1.29, 95% CI 1.08\u20131.53, p = 0.009) remained significantly worse in the high-risk group. Objective response (25.1% vs. 19.9%, p = 0.200) and disease control rates (71.7% vs. 76.5%, p = 0.262) were comparable. Among 103 responders with documented response-onset dates, an exploratory complete-case analysis showed a numerically shorter duration of response in the high-risk group, although the difference did not reach statistical significance (median, 7.1 vs. 11.3 months; HR, 1.57; 95% CI, 0.97\u20132.55; p = 0.065). Conclusions: Ate\/Bev achieved similar antitumor response rates in high-risk and non-high-risk patients, but survival remained poorer in the high-risk group. High-risk status therefore did not preclude antitumor activity with Ate\/Bev.<\/jats:p>","DOI":"10.3390\/cancers18182932","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:07:41Z","timestamp":1789027661000},"page":"2932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discordant Antitumor Efficacy with Compromised Survival in High-Risk Unresectable Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8413-7306","authenticated-orcid":false,"given":"Young Eun","family":"Seo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Joong","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4328-3955","authenticated-orcid":false,"given":"Jun Sik","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-9233","authenticated-orcid":false,"given":"Yang-Hyun","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Wool","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dong-A University College of Medicine, Busan 49315, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1619-2660","authenticated-orcid":false,"given":"Woo Sun","family":"Rou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1034-4478","authenticated-orcid":false,"given":"Jeong Eun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Daegu Catholic University Medical Center, School of Medicine, Catholic University of Daegu, Daegu 42472, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonho","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Mi","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Pusan National University Yangsan Hospital, Pusan National University, Yangsan 50615, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Dongnam Institute of Radiologic & Medical Sciences, Busan 46033, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Chin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52725, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Pyo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52725, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Young","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, College of Medicine, Pusan National University, Busan 49241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-7851","authenticated-orcid":false,"given":"Jeong","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, College of Medicine, Pusan National University, Busan 49241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Rim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-4396","authenticated-orcid":false,"given":"Soo Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Young","family":"Tak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-2496","authenticated-orcid":false,"given":"Jae Hyun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Bum","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju 61469, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1056\/NEJMra1713263","article-title":"Hepatocellular Carcinoma","volume":"380","author":"Villanueva","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular carcinoma","volume":"400","author":"Vogel","year":"2022","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41575-021-00438-0","article-title":"Advances in immunotherapy for hepatocellular carcinoma","volume":"18","author":"Sangro","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1200\/JCO.23.02745","article-title":"Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update","volume":"42","author":"Gordan","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jhep.2021.11.030","article-title":"Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma","volume":"76","author":"Cheng","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Himmelsbach, V., Pinter, M., Scheiner, B., Venerito, M., Sinner, F., Zimpel, C., Marquardt, J.U., Trojan, J., Waidmann, O., and Finkelmeier, F. (2022). Efficacy and Safety of Atezolizumab and Bevacizumab in the Real-World Treatment of Advanced Hepatocellular Carcinoma: Experience from Four Tertiary Centers. Cancers, 14.","DOI":"10.3390\/cancers14071722"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/hep.32468","article-title":"Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study","volume":"76","author":"Fulgenzi","year":"2022","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Iwamoto, H., Shimose, S., Noda, Y., Shirono, T., Niizeki, T., Nakano, M., Okamura, S., Kamachi, N., Suzuki, H., and Sakai, M. (2021). Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice. Cancers, 13.","DOI":"10.3390\/cancers13112786"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1007\/s10637-021-01185-4","article-title":"Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice","volume":"40","author":"Hayakawa","year":"2022","journal-title":"Investig. New Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/liv.15102","article-title":"Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma","volume":"42","author":"Cheon","year":"2022","journal-title":"Liver Int."},{"key":"ref_13","first-page":"655","article-title":"Efficacy and Safety of Atezolizumab plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma with Main Trunk and\/or Contralateral Portal Vein Invasion in IMbrave150","volume":"13","author":"Finn","year":"2024","journal-title":"Liver Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hwang, S.Y., Woo, H.Y., Heo, J., Kim, H.J., Park, Y.J., Yi, K.Y., Lee, Y.R., Park, S.Y., Chung, W.J., and Jang, B.K. (2024). Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma. Cancers, 16.","DOI":"10.3390\/cancers16040838"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","article-title":"Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach-the ALBI grade","volume":"33","author":"Johnson","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100557","DOI":"10.1016\/j.jhepr.2022.100557","article-title":"The ALBI score: From liver function in patients with HCC to a general measure of liver function","volume":"4","author":"Toyoda","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1111\/liv.14223","article-title":"Biology and significance of alpha-fetoprotein in hepatocellular carcinoma","volume":"39","author":"Galle","year":"2019","journal-title":"Liver Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2394268","DOI":"10.1080\/21645515.2024.2394268","article-title":"Prognostic value of the neutrophil-to-lymphocyte ratio and prognostic nutritional index in unresectable hepatocellular carcinoma patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors","volume":"20","author":"Sun","year":"2024","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wu, Y.L., Fulgenzi, C.A.M., D\u2019Alessio, A., Cheon, J., Nishida, N., Saeed, A., Wietharn, B., Cammarota, A., Pressiani, T., and Personeni, N. (2022). Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Prognostic Biomarkers in Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab. Cancers, 14.","DOI":"10.3390\/cancers14235834"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1002\/cam4.3135","article-title":"Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti-PD-1 therapy","volume":"9","author":"Dharmapuri","year":"2020","journal-title":"Cancer Med."},{"key":"ref_21","unstructured":"European Association for the Study of the Liver (2025). EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J. Hepatol., 82, 315\u2013374."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.jhep.2021.11.018","article-title":"BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update","volume":"76","author":"Reig","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_23","unstructured":"National Cancer Institute (2017). Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e71655","DOI":"10.1002\/cam4.71655","article-title":"Durable Disease Control With Atezolizumab Plus Bevacizumab but Limited Post-Progression Outcomes: A Multicenter Real-World Study in Advanced Hepatocellular Carcinoma","volume":"15","author":"Inoue","year":"2026","journal-title":"Cancer Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1159\/000544981","article-title":"Depth and Duration of Response Are Associated with Survival in Patients with Unresectable Hepatocellular Carcinoma: Exploratory Analyses of IMbrave150","volume":"14","author":"Kudo","year":"2025","journal-title":"Liver Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1158\/1078-0432.CCR-14-0122","article-title":"Intratumor heterogeneity in hepatocellular carcinoma","volume":"21","author":"Friemel","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.acra.2022.08.010","article-title":"Effect of Biliary Tract Invasion with Obstructive Jaundice on the Prognosis of Patients With Unresectable Hepatocellular Carcinoma","volume":"30","author":"Jiang","year":"2023","journal-title":"Acad. Radiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"877","DOI":"10.5009\/gnl240032","article-title":"Effect of Biliary Drainage on the Prognosis of Patients with Hepatocellular Carcinoma and Bile Duct Invasion","volume":"18","author":"Yang","year":"2024","journal-title":"Gut Liver"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.livres.2024.09.002","article-title":"Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?","volume":"8","author":"Abdelhamed","year":"2024","journal-title":"Liver Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/HEP.0000000000001182","article-title":"Distinct immune microenvironment of venous tumor thrombus in hepatocellular carcinoma at single-cell resolution","volume":"82","author":"Zhou","year":"2025","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Feng, M., and Granito, A. (2026). Foxp3(+) Tregs in HCC immunity and immunotherapy. Trends Mol. Med.","DOI":"10.1016\/j.molmed.2026.05.004"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:06:47Z","timestamp":1789988807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":31,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18182932"],"URL":"https:\/\/doi.org\/10.3390\/cancers18182932","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}