{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T22:01:38Z","timestamp":1793916098539,"version":"4.8.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"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>Treatment options for Barcelona Clinic Liver Cancer (BCLC) Stage C hepatocellular carcinoma (HCC) remain limited, with targeted therapy combined with immune checkpoint inhibitors (ICIs) serving as the standard first-line treatment. This study investigates whether a combination of transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), donafenib, and ICIs (quadruple therapy) provides superior survival benefits compared to the targeted therapy combined with ICIs (targeted-immunotherapy).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of patients with BCLC stage C HCC who received quadruple therapy or targeted-immunotherapy at the Harbin Medical University Cancer Hospital between September 2019 and October 2024The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), Disease Control Rate (DCR) and safety. To minimize baseline imbalances between the groups, we applied stabilized inverse probability of treatment weighting (sIPTW) methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 195 patients were included in the study, of whom 125 were assigned to the quadruple therapy group and 70 to the targeted-immunotherapy Group. After applying sIPTW to balance the baseline characteristics between the two groups, patients in the quadruple therapy group demonstrated a significantly higher median OS (mOS) compared with the targeted-immunotherapy group (29.4 months [95% CI: 23.9-NA] vs 18.0 months [14.7-31.8]; P = 0.041). Additionally, the median PFS (mPFS) assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was longer in the quadruple therapy group(16.4 months [95% CI: 12.7-NA] vs 10.0 months [3.32-31.8]; P = 0.012). Under the mRECIST criteria, quadruple therapy group demonstrated superior)ORR (68.4% vs 28.%, P = 0.001) and DCR (92.3% vs 63.1%, P &amp;lt; 0.001). The incidence of any adverse events (AE) in the quadruple therapy group was 95.2%, compared with 97.1% in the targeted-immunotherapy group. Among these the incidence of grade \u22653 AE was 40.8% in the quadruple therapy group and 38.6% in the targeted-immunotherapy group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Compared with targeted-immunotherapy group, patients with BCLC stage C HCC treated with TACE-HAIC combined with donafenib and ICIs demonstrated superior efficacy and acceptable safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1669856","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:59:02Z","timestamp":1762847942000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["TACE-HAlC combined with Donafenib and immune checkpoint inhibitors for BCLC stage C HCC patients (THEME study): a retrospective IPTW-adjusted cohort 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