{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:58:44Z","timestamp":1773809924936,"version":"3.50.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"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>Purpose<\/jats:title><jats:p>To evaluate the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (PA-HAIC) combined with lenvatinib and PD-1 inhibitors versus PA-HAIC with lenvatinib alone in patients with solitary large hepatocellular carcinoma (HCC, &amp;gt;5 cm).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 183 patients who underwent curative resection and subsequent PA-HAIC plus lenvatinib (HAIC-L, n = 108) or PA-HAIC combined with lenvatinib and PD-1 inhibitors (HAIC-L-P, n = 75) were enrolled from three centers between April 2021 and April 2023. Propensity score matching (PSM) was applied to balance baseline characteristics. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan\u2013Meier method and Cox proportional hazards models, while treatment-related adverse events (TRAEs) were compared between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The HAIC-L-P group demonstrated significantly improved DFS compared to the HAIC-L group both before (HR: 0.570; P = 0.007) and after PSM (HR: 0.518; P = 0.018). In contrast, no statistically significant difference was observed in OS between the two groups. Multivariate analysis identified elevated AFP (\u2265400 ng\/mL), microvascular invasion, and treatment strategy (HAIC-L <jats:italic>vs<\/jats:italic>. and HAIC-L-P) as independent predictors of DFS. Additionally, the overall safety profiles were comparable, with similar incidences of TRAEs and no significant increase in hepatic toxicity with PD-1 inhibitor addition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PA-HAIC combined with lenvatinib and PD-1 inhibitors significantly enhances DFS in patients with solitary large HCC, offering a promising adjuvant approach with acceptable safety. Further prospective, biomarker-driven trials are warranted to validate these findings and optimize patient selection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1609352","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T05:18:44Z","timestamp":1756271924000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and safety of postoperative adjuvant HAIC combining lenvatinib with or without PD-1 inhibitors in solitary large HCC: A multicenter retrospective 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