Survival outcomes of intensity-modulated radiotherapy combined with immunotherapy and targeted therapy for hepatocellular carcinoma with classification I-IV portal vein tumor thrombus: a propensity score matching study.

PURPOSE: The study aimed to evaluate the efficacy and safety of intensity-modulated radiotherapy (IMRT) combined with immunotherapy and targeted therapy (IT) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) classification I-IV. PATIENTS AND METHODS: The study analyzed HCC patients with PVTT who received IMRT combined with immunotherapy and targeted therapy (RT+IT, n = 176) or immunotherapy and targeted therapy alone (IT, n = 136). Propensity score matching (PSM) was performed to reduce baseline imbalance. Comparisons were made between the two groups in overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Subgroup analyses were further conducted to evaluate OS and PFS across PVTT classification I-IV. Cox regression analysis was performed to identify independent prognostic factors in patients receiving RT+IT. RESULTS: Following PSM, 97 pairs of participants were matched. In RT+IT, the median OS was longer (27.63 months, 95% CI: 20.00-33.00) compared to IT (17.57 months, 95% CI: 15.20-22.10), with a hazard ratio (HR) of 0.467 (95% CI: 0.323-0.675, p < 0.001). The cumulative OS rates at 3, 6, 12, 24, and 36 months were 99.0%, 96.9%, 83.3%, 54.2%, and 27.6% for RT+IT vs. 99.0%, 91.6%, 76.8%, 27.1%, and 12.2% for IT (p < 0.001). RT+IT had a longer median PFS (12.30 months,95% CI: 10.47-16.45) than IT (7.20 months, 95% CI: 6.37-9.67) (p < 0.001). Subgroup analysis by PVTT classification revealed that RT+IT was associated with improved OS and PFS across PVTT I, II, III, and IV than IT. Grade 3-4 adverse events between the two groups had no significant statistical difference. Biologically effective dose (BED10, α/β = 10 Gy), alpha fetoprotein (AFP), Child-Pugh (CP) grade, Cheng's classification of PVTT, and combined transcatheter chemoembolization (TACE) were identified as independent predictors of OS in patients who underwent RT+IT. CONCLUSION: IMRT combined with immunotherapy and targeted therapy was associated with improved survival outcomes with a manageable safety profile in HCC patients with PVTT across classification I-IV.