{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:04:42Z","timestamp":1791475482950,"version":"4.3.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"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><jats:title>Background<\/jats:title><jats:p>PD-1\/PD-L1 inhibitors have shown efficacy in improving the prognosis of patients with hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT) in pivotal clinical trials including the landmark IMbrave150 study. However, not all the patients benefit from the PD-1\/PD-L1 blockade immunotherapy. This study aimed to improve the identification of PVTT-associated HCC patients who may benefit from the combination of PD-1 inhibitor and hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitor (TKI) treatment under real-world conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From 377 HCC-PVTT patients receiving HAIC-TKI \u00b1 PD-1 inhibitors (2016-2023), we compared 76 dual-therapy (HT) and 175 triple-therapy (HTP) cases. Median follow-up period was 34.8 months in the HT group and 33.4 months in the HTP group (<jats:italic>P<\/jats:italic>=0.175). Propensity score matching (1:1 caliper=0.2) was used to balance baseline characteristics. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were evaluated in both groups. Specific subgroups including Vp4 type PVTT, extrahepatic metastases, and patients over 60 years old, were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Triple therapy significantly improved median OS (24.6 vs. 13.5 months; HR=0.58, 95%CI:0.42\u20130.80; <jats:italic>P<\/jats:italic>=0.001) and PFS (11.1 vs. 6.4 months; HR=0.56, <jats:italic>P<\/jats:italic>&amp;lt;0.001), with a 15% absolute ORR increase (66.3% vs. 51.3%, <jats:italic>P<\/jats:italic>=0.034). In subgroup analysis, for patients with Vp4 type PVTT, the addition of PD-1 inhibitor prolonged overall survival by 6.0 months (<jats:italic>P<\/jats:italic>=0.04). For patients aged 60 years and above, the addition of PD-1 inhibitor prolonged overall survival by 1.9 months (<jats:italic>P<\/jats:italic>=0.363). For patients with extrahepatic metastasis, the addition of PD-1 inhibitor prolonged overall survival by 3.0 months (<jats:italic>P<\/jats:italic>=0.913). Grade 3\u20134 adverse events were comparable (30.9% vs. 19.7%, <jats:italic>P<\/jats:italic>=0.09), but two patients experienced immune treatment-related fatalities in the HTP group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The triple therapy (HAIC-TKI-PD-1) demonstrated superior efficacy over HAIC-TKI dual therapy in HCC patients with PVTT, achieving significant improvements in ORR, mOS, and mPFS, with an acceptable safety profile. However, PD-1 inhibitors showed minimal survival benefits in patients aged &amp;gt;60 or with extrahepatic metastases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1602031","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T05:20:39Z","timestamp":1749705639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["PD-1 inhibitor-augmented HAIC-TKI therapy in hepatocellular carcinoma with portal vein tumor thrombosis: real-world survival benefits, safety, and subgroup-specific efficacy"],"prefix":"10.3389","volume":"16","author":[{"given":"Fei","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyong","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanggang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujun","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaojun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S318070","article-title":"Portal vein tumor thrombosis and hepatocellular carcinoma \u2013 the changing tides","volume":"8","author":"Khan","year":"2021","journal-title":"J Hepatocell Carcinoma"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000523997","article-title":"Guidelines for diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus in China (2021 edition)","volume":"11","author":"Sun","year":"2022","journal-title":"Liver Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290145","article-title":"Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials","volume":"29","author":"Llovet","year":"1999","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.cancergen.2024.06.002","article-title":"Cancer treatments: Past, present, and future","author":"Sonkin","year":"2024","journal-title":"Cancer Genet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1097\/ot9.0000000000000039","article-title":"Overview of perspectives on cancer, newer therapies, and future directions","volume":"10","author":"Joshi","year":"2024","journal-title":"Oncol Trans Med"},{"key":"B7","doi-asserted-by":"publisher","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":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.101567","article-title":"The management of hepatocellular carcinoma. 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