Revisiting HAIC and systemic treatment for initially diagnosed HCC with major portal vein (Vp3/4) tumor thrombosis

Abstract

Hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) has a dismal survival expectancy. The treatment for HCC with major PVTT remains challenging. The aim of the study was to revisit the survival outcomes and safety of locoregional hepatic arterial infusion chemotherapy (HAIC) and systemic treatment of immune checkpoint inhibitors (ICIs) and targeted therapy for initially diagnosed HCC patients with major PVTT. For this retrospective study, we enrolled 331 initially diagnosed HCC patients with major PVTT (Vp3/4) treated with HAIC plus systemic treatment of ICIs and/or targeted therapy between December 2018 and April 2024. The demographic and laboratory data, treatment allocations, tumor response, survival, and occurrence of adverse events were recorded. Survival outcomes and safety of the treatments were analyzed. Univariable and multivariable Cox regression analyses were conducted to identify predictive factors for overall survival (OS) and progression-free survival (PFS). In the patients with Vp3/4 PVTT receiving HAIC plus ICIs and/or targeted therapy, the median PFS and OS were 10.0 [95% confidence interval (CI), 8.7–14.3] months and 15.0 (95% CI, 13.2–16.8) months, respectively. The objective response rate (ORR) according to RECIST1.1 was 61.3%. On multivariate analysis, age, aspartate aminotransferase (AST), alkaline phosphatase (ALP), c-reactive protein (CRP), Child-Pugh grade, and metabolic comorbidity were prognostic factors associated with OS, while AST, ALP, CRP, extrahepatic metastasis (EHM), and metabolic comorbidity were prognostic factors associated with PFS. The most common grade 3–4 adverse events were thrombocytopenia (7.6%), elevated total bilirubin (7.6%), elevated transaminases (7.3%), upper gastrointestinal bleeding (7.3%), fever (7.6%), and ascites (5.4%). There was no treatment-related death. Locoregional HAIC in combination with systemic treatment of ICIs and/or targeted therapy preliminarily exhibits satisfactory anti-tumor activity for initially diagnosed HCC patients with Vp3/4 PVTT. The better survival outcomes can be expected under consideration of favorable prognostic factors including age ≤ 62.5 years, Child-Pugh grade A, AST ≤ 63.5 U/L, ALP ≤ 176.5 U/L, CRP ≤ 17.8 mg/L, no extrahepatic metastasis, and coexistence of metabolic comorbidity, which are hypothesis-generating observations and need external and prospect studies.