{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:04:45Z","timestamp":1788015885006,"version":"build-2784847793"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"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>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) with VP4 portal vein tumor thrombosis (PVTT) has a poor prognosis. Although hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed cell death protein 1 (PD-1) inhibitors shows activity in advanced HCC with PVTT, whether adding PD-1 inhibitors to HAIC plus TKIs improves outcomes specifically in VP4 PVTT remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective study enrolled consecutive treatment-na\u00efve patients with advanced HCC and VP4 PVTT who received HAIC plus TKIs (dual therapy) or HAIC plus TKIs and PD-1 inhibitors (triple therapy) from January 2018 to July 2025. Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize selection bias. Primary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ninety-seven patients were included: 43 in the dual therapy group and 54 in the triple therapy group. Median follow-up was 42.3 months. After sIPTW adjustment, triple therapy achieved a higher ORR (58.9% vs 31.4%, P\u00a0=\u00a00.012) and disease control rate (94.8% vs 72.1%, P\u00a0=\u00a00.003). PVTT ORR was also higher with triple therapy (49.9% vs 26.5%, P\u00a0=\u00a00.034). Triple therapy was associated with longer sIPTW-adjusted median PFS (7.3 vs 5.5 months; HR 0.48, 95% CI 0.31\u20130.75, P\u00a0=\u00a00.001) and OS (14.6 vs 10.1 months; HR 0.47, 95% CI 0.29\u20130.74, P\u00a0=\u00a00.001). Multivariable Cox regression identified treatment regimen and baseline neutrophil-to-lymphocyte ratio as independent prognostic factors for both PFS and OS. Grade 3\u20134 treatment-related adverse events were comparable (35.2% vs 30.2%, P\u00a0=\u00a00.606), with no treatment-related deaths.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with advanced HCC and VP4 PVTT, the addition of PD-1 inhibitors to HAIC plus TKIs was associated with improved tumor response and prolonged survival without an apparent increase in severe treatment-related adverse events. These findings support triple therapy as a potentially preferred first-line strategy for this high-risk population. Prospective randomized trials are needed to validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1832313","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:39:30Z","timestamp":1779255570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatic arterial infusion chemotherapy plus tyrosine kinase inhibitors with or without PD-1 inhibitors for advanced hepatocellular carcinoma with VP4 portal vein tumor thrombosis: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Weifu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oncology and Vascular Interventional Therapy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Tumor Biotherapy","place":["Fuzhou, 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