Hepatic Arterial Infusion Chemotherapy in the Treatment of Unresectable Hepatocellular Carcinoma with and Without Extrahepatic Spread: A Propensity Score Matching Study

<b>Purpose:</b> We aimed to study the efficacy and safety of hepatic artery infusion chemotherapy (HAIC) in the treatment of unresectable hepatocellular carcinoma (HCC) with extrahepatic spread (EHS). <b>Materials and Methods:</b> A total of 323 patients with unresectable HCC received HAIC plus lipiodol microvascular embolization. HAIC was performed via puncture of the left subclavian artery with a temporary 4-French angio-catheter placed in the common/proper hepatic artery. The HAIC regimen consisted of a daily infusion of cisplatin (10 mg/m²), mitomycin-C (2 mg/m²), and leucovorin (15 mg/m²), administered over a period of 20-30 min, and then a 5-fluorouracil (5-FU, 100 mg/m²) infusion for the remaining of 22 h of each day, for five consecutive days. Before the temporary catheter was removed, 10 mL of ethiodized oil (Lipiodol, Guerbet, France) was injected to obtain a synergistic effect of chemoinfusion and lipiodol microvascular embolization. Treatment responses were evaluated based on mRECIST criteria. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients with EHS were compared to those without. Subgroup analyses of patients with and without major portal vein tumor thrombosis (PVTT) were performed both before and after propensity score matching (PSM). The survival analyses were conducted with the Kaplan-Meier method and compared using the log-rank test. All the statistical analyses were performed by SPSS (version 26.0). <b>Result:</b> The overall ORR was 59.1%. The median OS of the initial cohort and patients positive and negative for EHS were 16.3, 12.0, and 18.0 months, respectively (<i>p</i> = 0.002). In the subgroup analysis, there was no statistical difference in survival in patients with major PVTT between the with-EHS and without-EHS groups (13.0 vs. 15.0 months, <i>p</i> = 0.407). However, the median OS in patients with EHS was significantly shorter than those without EHS (11.4 vs. 19.4 months, <i>p</i> < 0.001) in the subgroup of non-major PVTT patients. After PSM, there were no significant survival differences between the EHS and non-EHS groups in any patient cohort or sub-cohort analysis. <b>Conclusions:</b> For unresectable HCC, controlling intrahepatic tumor progression through HAIC is more important than controlling extrahepatic tumor growth, especially in patients with major PVTT. Personalized locoregional HAIC can be performed in patients with EHS.