Time-dependent efficacy of tumor burden score in hepatocellular carcinoma treated with transarterial chemoembolization

Abstract

Tumor Burden Score (TBS) is an emerging prognostic indicator for hepatocellular carcinoma (HCC). We aimed to evaluate the long-term prognostic efficacy, time-dependent discrimination, and treatment response associations of TBS in patients with HCC undergoing transarterial chemoembolization (TACE). We analyzed 178 treatment-naïve HCC patients who underwent TACE. Survival outcomes were assessed using Kaplan-Meier curves, subgroup stratifications (BCLC stage, ALBI grade), and time-dependent Cox regression. Model discrimination was evaluated using time-dependent ROC and Harrell’s C-index. Independent predictors of mortality were identified using multivariate analyses. The median overall survival (OS) was 28 months (IQR: 18–58). Baseline continuous TBS significantly predicted OS; however, time-interaction analysis confirmed a time-dependent decay (p < 0.05), with hazard discrimination peaking early before attenuating during follow-up. Adding continuous TBS to a baseline staging model improved the 1-year AUC from 0.640 to 0.649 ($$\Delta \text{AUC}=0.009$$-->), whereas incremental shifts were negligible at 3 years ($$0.630\,\text{vs.}\,0.631$$-->, $$\Delta \text{AUC}=0.001$$-->) and 5 years ($$0.576\,\text{vs.}\,0.577$$-->, $$\Delta \text{AUC}=0.001$$-->), alongside a minimal change in overall C-index ($$0.581\,\text{vs.}\,0.582$$-->). Standalone continuous TBS showed peak discrimination at 1 year (AUC: 0.633), attenuating at 3 years (AUC: 0.570) and 5 years (AUC: 0.510). Subgroup analyses revealed significant survival stratifications by TBS tier at 3 years for BCLC B/C (p = 0.046) and ALBI 2/3 (p = 0.03) patients. TBS was significantly correlated with microvascular invasion (p = 0.03) and worse post-TACE response [(stable disease ($${\text{OR}}={1.365,95} \% \,{\text{CI}}:1.122-1.661,p=0.002$$-->) /progressive disease ($${\text{OR}}=1.381,95 \% \,{\text{CI}}:1.151-1.658,p=0.001$$--> )). In multivariate analysis, TBS remained an independent predictor of overall mortality (HR: 1.368, 95% CI: 1.030–1.815, p = 0.03). Baseline TBS is independently associated with overall mortality and non-response following TACE in patients with HCC. However, its predictive discrimination exhibits significant time-dependent attenuation, offering maximal prognostic value during the early post-treatment follow-up.