The METAL Score for Early Stratification of Radiological Response and Survival in Hepatocellular Carcinoma Treated
Qian Chen1, Long-Wang Lin1, Zhi-Cheng Jin1
1Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China (Q.C., L.W.L., Z.C.J., J.J.C., H.D.Z., G.J.T.); National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Southeast University, Nanjing, China (Q.C., L.W.L., Z.C.J., H.D.Z., G.J.T.).
Rationale And Objectives:
To develop and validate a prognostic stratification tool for patients with unresectable hepatocellular carcinoma (uHCC) receiving transarterial chemoembolization (TACE) combined with targeted and immunotherapy (triple therapy).
Materials And Methods:
This multicenter retrospective study included uHCC patients treated with first-line triple therapy at 13 tertiary hospitals from December 2018 to August 2023. A prognostic score was developed (n=378) based on multivariate Cox regression and validated in an external cohort (n=148). Radiological response and overall survival (OS) were assessed across different risk strata. Score performance was compared to existing prognostic models and further evaluated in a separate cohort receiving systemic therapy without TACE (n=232).
Results:
A three-variable score (METAL) integrating metastatic burden, alpha-fetoprotein, and albumin-bilirubin grade was developed. Median OS for low-, intermediate-, and high-risk groups was 30.8, 25.2, and 11.6 months in the derivation cohort, and 34.6, 23.0, and 14.8 months in the external validation cohort, respectively (all p<0.001). In both cohorts, confirmed objective response rates (ORR) also declined progressively across risk strata (all p<0.001). The current score was superior to existing TACE- or immunotherapy-related models, with higher discrimination and lower prediction error (C-index, 0.70 and 0.70; integrated Brier score, 0.140 and 0.122 in the derivation and validation cohorts, respectively). The METAL-low score successfully identified a subgroup achieving significantly longer OS (32.6 vs. 23.8 months; p=0.034) and higher ORR (77.2% vs. 48.1%; p<0.001) with triple therapy compared to systemic therapy alone.
Conclusion:
The proposed METAL score enables early identification of ideal uHCC candidates most likely to benefit from triple therapy.
