Efficacy of Locoregional HAIC and Systemic Treatment for Treatment- Naive Unresectable Hepatocellulcar Carcinoma.

Background and Aim: Unresectable hepatocellular carcinoma (u-HCC) is highly heterogeneous, with limited survival expectancy. The aim of this study was to reappraise the efficacy and safety of locoregional hepatic arterial infusion chemotherapy (HAIC)combined with systemic treatment in initially diagnosed u-HCC. Methods: A total of 302 treatment-naive patients with u-HCC who received HAIC and systemic treatment therapy between December 2018 and November 2023 were enrolled. The cumulative progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors affecting survival were analyzed via Cox regression analysis. Results: The median PFS and OS were 11.5 (95% CI: 8.7-14.3) months and 30.0 (95% CI: 20.7-39.2) months, respectively. The estimated PFS rates were 66.2%, 47.9% and 35.2% at 0.5, 1 and 2 years, respectively, and the estimated OS rates were 68.0%, 52.5% and 41.7% at 1, 2, and 3 years, respectively. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), neutrophil to lymphocyte ratio (NLR), extrahepatic metastasis (EHM), metabolic comorbidity and treatment allocation were identified as factors associated with patient survival. The treatment regimen was well tolerated. Conclusion: Locoregional HAIC combined with systemic immune checkpoint inhibitors (ICIs) and targeted therapy represents an effective and safe treatment modality for initially diagnosed u-HCC. Favorable survival outcomes were associated with AST ≤ 56.5 U/L, ALP ≤ 174.5 U/L, NLR ≤ 1.77, absence of extrahepatic metastasis, presence of metabolic comorbidity, and HAIC combined with ICI plus targeted/anti-VEGF therapy. These findings require further validation in external and prospective cohorts.