The ATC score: a novel efficacy scoring model for risk stratification and personalized management of unresectable HCC patients receiving TACE-lenvatinib-PD-1 inhibitor therapy

Abstract

Unresectable Hepatocellular Carcinoma (uHCC) has limited therapeutic options. The combination therapy of Transarterial chemoembolization (TACE), lenvatinib, and PD-1 inhibitors (T-L-P) shows promising efficacy, but a tool to predict individual treatment responses is lacking. To develop and validate an efficacy scoring model for uHCC patients undergoing T-L-P therapy. This retrospective study included 154 uHCC patients receiving initial T-L-P therapy between 2020 and 2022. Patients were divided into training ( n = 90) and validation ( n = 64) cohorts. Independent factors associated with Objective Response Rates (ORR) were identified by univariate and multivariate logistic regression analyses. An efficacy scoring model was constructed using these factors. Overall Survival (OS) and Progression Free Survival (PFS) were evaluated by Kaplan-Meier analysis. The model performance was assessed by the area under the curve (AUC). The ORR and Disease Control Rate (DCR) were 48.9 (44/90) and 80.0% (72/90) in the training cohort, and 59.4% (38/64) and 81.3% (52/64) in the validation cohort, respectively. Multivariate analysis identified Alpha-fetoprotein (AFP) > 100 ng/mL (OR = 3.270), Tumor Burden Score (TBS) > 8 (OR = 3.474), and Child-Pugh B stage (OR = 3.163) as independent predictors of ORR in the training cohort (all p < 0.05), confirmed in the validation cohort. Based on the above variables, we established an efficacy scoring model, naming ATC score (range 0–3; 1 point per factor), which stratified patients into low-risk (score 0), intermediate-risk (score 1), and high-risk (score ≥ 2) groups. In the training cohort, the 2-year OS rates were 83.57% for score 0, 64.13% for score 1, and 20.69% for score ≥ 2. The 2-year PFS rates were 66.48%, 46.55%, and 9.33%, respectively. In the validation cohort, the 2-year OS rates were 94.12% for score 0, 64.71% for score 1, and 25.93% for score ≥ 2. The 2-year PFS rates were 82.35%, 47.06%, and 16.67%, respectively. The ATC score exhibited superior predictive accuracy (training AUC: 0.826; validation AUC: 0.811) compared to its individual components. The novel ATC score effectively stratifies uHCC patients receiving T-L-P therapy into efficacy groups, guiding personalized treatment decisions.