Efficacy and safety of Y90 radioembolization combined with targeted therapy and immunotherapy in patients with unresectable hepatocellular carcinoma: a dual-center, retrospective study

Patients with unresectable hepatocellular carcinoma (uHCC) have a poor prognosis and limited treatment options. The combination of transarterial radioembolization (TARE) with yttrium-90 (Y90), targeted therapy, and immunotherapy represents a novel integrated approach, yet real-world evidence regarding its efficacy and safety remains scarce. In this dual-center retrospective study, 32 patients with uHCC who received combined therapy with TARE, a targeted agent and an immune checkpoint inhibitor were enrolled. Tumor response was evaluated according to mRECIST and RECIST 1.1. Survival outcomes were analyzed using the Kaplan–Meier method, and prognostic factors were identified through Cox regression analyses. Among the 32 patients (87.5% male, 93.8% HBV-related), 71.9% had a maximum tumor diameter ≥10 cm, 53.1% had Vp3/4 portal vein tumor thrombosis, and 31.2% had extrahepatic metastasis. The objective response rate was 71.9% by mRECIST and 50.0% by RECIST 1.1. After a median follow-up of 12 months (IQR: 9–14.3), median progression-free survival was 10.5 months (95% CI: 7.4–13.6), and median overall survival was 17.0 months (95% CI: 11.5–22.5). A baseline alpha-fetoprotein level ≥400 ng/mL was identified as an independent adverse prognostic factor for both progression-free survival (HR = 2.755, p = 0.033) and overall survival (HR = 4.189, p = 0.029). Grade 3–4 treatment-related adverse events occurred in 43.8% of patients, with no treatment-related deaths. In conclusion, this real-world study provides preliminary evidence that the triple-modality regimen of TARE, targeted therapy, and immunotherapy has encouraging antitumor activity and a manageable safety profile in patients with uHCC, suggesting its potential as a feasible treatment strategy for this high-risk population.