{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:39:45Z","timestamp":1767206385487,"version":"build-2238731810"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the short-term efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in patients with hepatocellular carcinoma (HCC) complicated by high-flow hepatic arteriovenous fistula (HAVF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed clinical data from 40 patients with unresectable HCC complicated by high-flow HAVF who received FOLFOX regimen HAIC plus ICIs and TKIs between January 2021 and June 2023. The efficacy evaluation included HAVF effective rate, tumor response, progression-free survival (PFS), overall survival (OS) per RECIST 1.1 and mRECIST. Adverse events (AEs) were recorded for safety evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The median follow-up time was 10.5 months (range: 3.5-16.4 months). A total of 150 HAIC cycles were administered, with a median frequency of 3.8 cycles per patient. The objective response rate (ORR) and the disease control rate (DCR) was 42.5% and 92.5% according to the RECIST 1.1, and 75.0% and 92.5% according to mRECIST criteria, respectively. The median PFS and the median OS were 5.5 months (95% CI: 3.9-6.9) and 10.4 months (95% CI: 7.4-13.4), respectively. In univariate analysis, HAVF grade, extrahepatic spread, HAVF disappearance were potential prognostic factors for OS, while HAVF grade and extrahepatic spread being independently associated with PFS. Hypertension (12.5%), Thrombocytopenia (12.5%) and Albumin decreased (7.5%) were the most frequently observed grade 3-4 TRAEs.No treatment-related mortality occurred during the study period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HAIC combined with ICIs and TKIs demonstrates promising short-term efficacy and acceptable safety in patients with unresectable HCC complicated by high-flow HAVF. This combination therapy effectively controls tumor growth while simultaneously managing the arteriovenous shunt, providing a valuable treatment option for this challenging patient population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1643290","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:33:12Z","timestamp":1754026392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Triple therapy revolutionizes treatment paradigms for previously untreatable HCC complicated by high-flow hepatic arteriovenous fistulas"],"prefix":"10.3389","volume":"16","author":[{"given":"Jinpeng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingtao","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiasheng","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lujun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlong","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24199","article-title":"American association for the study of liver diseases","volume":"53","author":"Bruix","year":"2011","journal-title":"Manage hepatocellular carcinoma: an update Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2007.01520.x","article-title":"Application of ultrasonography in the diagnosis and treatment tracing of hepatocellular carcinoma-associated arteriovenous fistulas","volume":"27","author":"Li","year":"2007","journal-title":"Liver Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-011-9338-z","article-title":"Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy","volume":"7","author":"Hsu","year":"2013","journal-title":"Hepatol Internat"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1277329","article-title":"Transarterial chemoembolization combined donafenib with\/without PD-1 for unresectable HCC in a multicenter retrospective study","volume":"14","author":"Li","year":"2023","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.11952\/j.issn.1007-1954.2024.03.003","article-title":"Short-term efficacy and safety of hepatic arterial infusion chemotherapy in the treatment of unresectable hepatocellular carcinoma with high-flow hepatic arterioportal shunts","volume":"36","author":"Chen","year":"2024","journal-title":"J Hepatopancreatobiliary Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.0250","article-title":"Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial","volume":"5","author":"He","year":"2019","journal-title":"JAMA Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01963","article-title":"Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase III trial (FOHAIC-1)","volume":"40","author":"Lyu","year":"2022","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"997","DOI":"10.3760\/j.issn:1005-1201.2002.11.009","article-title":"Transmicrocatheter local injection of ethanol to treat hepatocellular carcinoma with high flow arteriovenous shunts","volume":"36","author":"Guan","year":"2002","journal-title":"Zhonghua Fangshexue Zazhi"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13429","article-title":"EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice","volume":"37","author":"Aub\u00e9","year":"2017","journal-title":"Liver Int"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s00270-017-1619-z","article-title":"Indicators of lung shunt fraction determined by Technetium-99?m macroaggregated albumin in patients with hepatocellular carcinoma","volume":"40","author":"Kallini","year":"2017","journal-title":"Cardiovasc Intervent Radiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-8179.20150370","article-title":"Imaging characteristics and intervention therapy for hepatic artery-portal vein shunts in patients with primary liver carcinoma","volume":"42","author":"Chen","year":"2015","journal-title":"Chin J Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12876-018-0899-3","article-title":"Clinical characteristics of hepatic Arterioportal shunts associated with hepatocellular carcinoma","volume":"18","author":"Wu","year":"2018","journal-title":"BMC Gastroenterol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/cancers4010165","article-title":"Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in Japan","volume":"4","author":"Nishikawa","year":"2012","journal-title":"Cancers (Basel)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvir.2014.11.002","article-title":"Arterioportal shunts in patients with hepatocellular carcinoma treated using ethanol-soaked gelatin sponge: therapeutic effects and prognostic factors","volume":"26","author":"Zhou","year":"2015","journal-title":"J Vasc Interv Radiol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i6.825","article-title":"Comparison of long-term effects between intra-arterially delivered ethanol and Gelfoam for the treatment of severe arterioportal shunt in patients with hepatocellular carcinoma","volume":"10","author":"Huang","year":"2004","journal-title":"World J Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.00608","article-title":"Hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin versus transarterial chemoembolization for large hepatocellular carcinoma: A randomized phase III trial","volume":"40","author":"Li","year":"2022","journal-title":"J Clin Oncol: Off J Am Soc Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2021.00100","article-title":"Hepatic arterioportal fistulas: A retrospective analysis of 97 cases","volume":"10","author":"Cao","year":"2022","journal-title":"J Clin Transl Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvir.2017.07.020","article-title":"Transarterial chemoembolization with small drug-eluting beads in patients with hepatocellular carcinoma: experience from a cohort of 421 patients at an italian center","volume":"28","author":"Aliberti","year":"2017","journal-title":"J Vasc Interv Radiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-014-0978-3","article-title":"A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis","volume":"50","author":"Song","year":"2015","journal-title":"J Gastroenterol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00270-017-1874-z","article-title":"Phase II study of sorafenib combined with concurrent hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin for unresectable hepatocellular carcinoma with major portal vein thrombosis","volume":"41","author":"He","year":"2018","journal-title":"Cardiovasc Intervent Radiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/s41392-022-01235-0","article-title":"Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001)","volume":"8","author":"Zhu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01663-6","article-title":"Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a Phase II study","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.954203","article-title":"Efficacy and safety of transarterial chemoembolization plus antiangiogenic- targeted therapy and immune checkpoint inhibitors for unresectable hepatocellular carcinoma with portal vein tumor thrombus in the real world","volume":"12","author":"Feng","year":"2022","journal-title":"Front Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1159\/000507262","article-title":"Increased arterio-portal shunt formation after drug-eluting beads TACE for hepatocellular carcinoma","volume":"98","author":"Shimose","year":"2020","journal-title":"Oncology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2007.8.4.311","article-title":"Polyvinyl alcohol embolization adjuvant to oily chemoembolization in advanced hepatocellular carcinoma with arterioportal shunts","volume":"8","author":"Kim","year":"2007","journal-title":"Korean J Radiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.607520","article-title":"Advanced hepatocellular carcinoma with hepatic arterioportal shunts: combination treatment of transarterial chemoembolization with apatinib","volume":"7","author":"Sun","year":"2020","journal-title":"Front Mol Biosci"}],"updated-by":[{"DOI":"10.3389\/fimmu.2025.1681008","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1643290\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:35:03Z","timestamp":1755599703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1643290\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":29,"alternative-id":["10.3389\/fimmu.2025.1643290"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1643290","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]},"article-number":"1643290"}}