Supplementary Material for: Age-adjusted Charlson Comorbidity Index Guides Risk Stratification for Hepatocellular Carcinoma Patients Treated with TACE Combined with Immune Checkpoint Inhibitors and Targeted Therapy: a multicenter retrospective cohort study

Background: Hepatocellular carcinoma (HCC) imposes a substantial global burden. Triple therapy including transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs) and targeted therapy offers survival benefits but increases toxicity risk. We aimed to evaluate the impact of age or its-related comorbidities on the efficacy and safety of triple therapy.
Methods: This multicenter retrospective study included 627 HCC patients receiving triple therapy from CLEAP database (2019–2023). Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. Treatment response and treatment-related adverse events (TRAEs) were the secondary endpoints. Cox/logistic regression models were used to assess the risk factors of outcomes.
Results: Of 627 patients, 177 were classified as elderly (≥ 65 years) and 450 as younger (< 65 years), as defined according to World Health Organization criteria. Elderly patients present with lower tumor burden compared with younger patients. After propensity score matching (1:2), two cohorts were comparable in objective response rate, disease control rate, PFS, OS and grade ≥ 3 TRAEs. Age, either continuous or categorical data, was not associated with outcomes. In contrast, stratification by Charlson Comorbidity Index (CCI), there were significant outcome disparities for PFS and OS among low- (0-1), intermediate- (2-3), and high-risk (≥ 4) groups. The age-adjusted CCI (aCCI) could not only discriminate survival outcomes, but also predict the risk of TRAEs among low- (0-3), intermediate- (4-5), and high-risk (≥ 6) groups. Multivariable analyses demonstrated that high aCCI score (≥ 6) independently predicted shorter PFS (hazard ratio: 1.36, p = 0.02) and OS (hazard ratio: 1.75, p = 0.001), and increased grade ≥ 3 TRAEs (odds ratio: 1.96, p = 0.005).
Conclusion: aCCI was a potent predictor of efficacy and safety in triple therapy for HCC.