66 - The METAL Score for Early Risk Stratification in Hepatocellular Carcinoma Treated with TACE and Immunotherapy Combinations

Purpose: Although transarterial chemoembolization (TACE) combined with immune-based systemic therapy represents a promising regimen for patients with unresectable hepatocellular carcinoma (uHCC), it remains unclear which subgroups are most likely to benefit. We aimed to develop and validate a prognostic tool for identification of ideal candidates.

Materials and Methods: This multicenter retrospective study included 526 uHCC patients who received first-line TACE plus targeted and immunotherapy at 13 tertiary hospitals between December 2018 and August 2023. A prognostic score was developed in a derivation cohort (n=378) using 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 benchmarked against 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 (HR 1.47 for oligometastases, p = 0.032; HR 4.31 for polymetastases, p < 0.001), log₁₀alpha-fetoprotein (HR 1.18, p = 0.006), and albumin-bilirubin grade (HR 1.50, p = 0.018) was developed, showing a linear association with mortality risk (overall p< 0.001; nonlinear p=0.556). 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 METAL score outperformed existing TACE- or immunotherapy-related models, showing 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). Additionally, 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% by mRECIST, p< 0.001; 49.7% vs.30.8% by RECIST v1.1, p=0.029) with combination therapy compared to systemic therapy alone.

Conclusion: The proposed METAL score enables pretreatment risk stratification in uHCC patients undergoing TACE-immunotherapy combinations and has the potential to facilitate individualized treatment decision-making in real-world settings.