Prognostic model for unresectable hepatocellular carcinoma treated with transarterial therapy plus TKIs and anti-PD-1 antibodies.

BACKGROUND: Transarterial therapy, including transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC), has long been a cornerstone in the management of unresectable hepatocellular carcinoma (uHCC). In parallel, the emergence of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein 1 (PD-1) antibodies has reshaped the systemic treatment landscape. Recently, the combination of transarterial therapy with TKIs and anti-PD-1 antibodies has shown promising efficacy in treating uHCC, but lacks a standardized prognostic model. METHODS: We retrospectively included 243 patients with uHCC treated with transarterial therapy plus TKIs and anti-PD-1 antibodies, divided into training (n = 169) and validation (n = 74) cohorts. Within the training cohort, Cox regression identified factors associated with overall survival (OS), forming a scoring model. Model performance was assessed using time-dependent receiver operating characteristic curves, calibration plots, and the concordance index. RESULTS: Multivariate analysis identified hepatitis B virus infection, largest tumor size pre-treatment, baseline neutrophil-to-lymphocyte ratio, and spleen volume at 6 weeks post-treatment as independent prognostic factors for OS. The HLNS score was constructed and stratified patients into low- and high-risk categories, with median OS of 34.6 vs. 7.3 months (p < 0.001), and objective response rates of 49.6% vs. 23.8% (p = 0.006). The model's performance was corroborated across both the validation and entire cohorts. CONCLUSION: The HLNS score provides a useful tool for personalized prognostication and risk classification of uHCC patients treated with transarterial therapy plus TKIs and anti-PD-1 antibodies.