{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:36Z","timestamp":1792790436778,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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>Objective<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with hepatic arterial infusion chemotherapy (HAIC), donafenib and camrelizumab in the treatment of unresectable hepatocellular carcinoma (uHCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective analysis enrolled patients with unresectable hepatocellular carcinoma (uHCC) from 4 Grade A tertiary hospitals in China, with data collected between December 2022 and December 2024. Patients were stratified into two groups based on their treatment modalities: the DEB-TACE-HAIC combined with donafenib and camrelizumab group (DHDC) and the DEB-TACE combined with donafenib and camrelizumab group (DDC). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized to assess and compare the objective response rate (ORR) and disease control rate (DCR) between the two cohorts. Survival curves were generated using the Kaplan-Meier method, and differences in progression-free survival (PFS) and overall survival (OS) were analyzed by the Log-rank test. Additionally, the Cox proportional hazards regression model was employed to identify independent prognostic factors for PFS and OS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 122 patients were ultimately enrolled in this study, with 58 patients were enrolled in the DHDC group and 64 patients were enrolled in the DDC group. Baseline characteristics were well balanced between the two groups. The median follow-up duration was 18 months in the DHDC group and 14 months in the DDC group. Before inverse probability of treatment weighting (IPTW) adjustment, the DHDC group had higher ORR (74.1% vs. 51.6%, P\u00a0=\u00a00.010) and DCR (91.4% vs. 75.0%, P\u00a0=\u00a00.017) than the DDC group. These advantages remained after IPTW adjustment (ORR: 72.5% vs. 53.4%, P\u00a0=\u00a00.036; DCR: 90.7% vs. 75.3%, P\u00a0=\u00a00.033). Kaplan\u2013Meier analysis showed that the DHDC group had longer median PFS (16 vs. 11 months, P &amp;lt; 0.001) and OS (28 vs. 18 months, P &amp;lt; 0.001) than the DDC group before IPTW adjustment; these differences remained after IPTW (PFS: 16 vs. 11 months, P &amp;lt; 0.001; OS: 28 vs. 19 months, P &amp;lt; 0.001).On multivariable Cox analysis, portal vein tumor thrombosis (PVTT) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007) and extrahepatic metastasis (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) were identified as independent risk factors for PFS, whereas treatment with the DHDC regimen was independently associated with improved PFS (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Similarly, PVTT (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.016) and extrahepatic metastasis (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) were independent predictors of poorer OS, while DHDC treatment remained an independent protective factor for OS (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Subgroup analyses consistently demonstrated clinically meaningful improvements in both PFS and OS with DHDC therapy across most prespecified clinical subgroups. Notably, more pronounced survival benefits were observed among male patients, those with hepatitis B virus infection, multiple tumors (&amp;gt;3), underlying cirrhosis, PVTT, extrahepatic metastasis, Barcelona Clinic Liver Cancer stage (BCLC) C disease, and tumor diameter greater than 10\u00a0cm. Although the DHDC group experienced a higher incidence of nausea and vomiting compared with the DDC group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), these adverse events were limited to grade 1\u20132 severity. No significant differences were observed between the two groups with respect to the overall incidence or severity of other adverse events (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with uHCC, the DHDC quadruple regimen was associated with improved survival outcomes while maintaining an acceptable safety profile. These findings suggest that a treatment strategy incorporating DEB-TACE\u2013HAIC in combination with targeted therapy and immunotherapy may represent a more effective therapeutic option for selected patients with uHCC, warranting further prospective investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1779170","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:11:35Z","timestamp":1780035095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["DEB-TACE-HAIC combined with donafenib and camrelizumab in the treatment of unresectable hepatocellular carcinoma: a multicenter retrospective study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuanjin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Interventional Medicine, The Second Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, 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