ArticleFrontiers in immunology2026
The SAGES scoring model leads to personalized treatment via the combination of TACE, TKIs and ICIs for unresectable hepatocellular carcinoma.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and aims: Transcatheter chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) shows promising efficacy in treating unresectable hepatocellular carcinoma (uHCC), but the specific patient population that would benefit most from this regimen remains unclear. This study aims to evaluate the prognoses of uHCC patients receiving triple therapy and develop a practical prognostic scoring model to identify those with the best beneficial. Methods: This multicenter retrospective study enrolled 270 uHCC patients who received first-line triple therapy across 20 centers. These participants were divided into the training (n=190) and external validation (n=80) cohorts. Treatment response was assessed by the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety was evaluated via treatment-related adverse events (TRAEs) using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Cox proportional hazards regression was used to identify independent prognostic factors for overall survival, which were utilized to develop the SAGES score; Kaplan-Meier curves and area under the receiver operating characteristic curve (AUC) were employed to validate the model's performance. Results: In the training cohort, the objective response rate was 47.9% and disease control rate was 63.2%. The median progression-free survival was 15.9 months, with 3-year overall survival and progression-free survival rates of 52.2% and 30.7%, respectively. Independent prognostic factors for poor overall survival included albumin-bilirubin grade 2-3, alpha-fetoprotein ≥400 ng/mL, maximum tumor size ≥8 cm, presence of extrahepatic metastasis, and absence of conversion surgery. Integrating these five factors, the SAGES score effectively stratified patients into low- (0-3 points), intermediate- (4-7 points), and high-risk (8-10 points) groups with significantly divergent survival outcomes in both cohorts (all p<0.001). The model exhibited robust discriminative ability, with AUCs of 0.78 in the training cohort and 0.75 in the validation cohort, outperforming individual prognostic factors. Conclusion: Triple therapy showed promising clinical outcomes and the SAGES score provides reliable prognostic stratification and facilitates personalized treatment decisions for uHCC patients receiving this triple regimen.
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