Post-TARE Survival Outcomes in Hepatocellular Carcinoma: Influence of Pre-TARE Immunotherapy and Targeted Therapy in a Real-World Cohort

Background: Transarterial radioembolization (TARE) combined with systemic therapy has shown activity in unresectable hepatocellular carcinoma (HCC). However, the prognostic impact of different treatment exposures before TARE in real-world practice remains unclear. Methods: This single-center retrospective study included 71 patients with HCC who underwent TARE between November 2022 and August 2025. TARE was defined as the unified clinical landmark for outcome assessment. Patients were stratified according to treatment exposure before TARE: those who received ≥ 2 cycles of immune checkpoint inhibitors combined with targeted therapy prior to TARE (Group 1) and those who underwent TARE as the initial major treatment (Group 2). Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. Cox regression analyses were performed to identify prognostic factors, including baseline neutrophil-to-lymphocyte ratio (NLR). Results: Group 2 achieved a significantly higher ORR than Group 1 (87.5% vs 56.4%, P = 0.004). Median PFS was significantly longer in Group 2 than in Group 1 (17.45 vs 4.86 months; hazard ratio = 0.327, 95% confidence interval: 0.125– 0.856, P = 0.023). No significant difference in OS was observed during the current follow-up period. Patients with baseline NLR ≤ 3.28 experienced significantly prolonged PFS compared with those with NLR > 3.28. Conclusion: In this real-world cohort, treatment exposure prior to TARE was associated with post-TARE PFS and tumor response, but not with OS. These findings suggest that baseline treatment history and systemic inflammatory status influence post-TARE prognosis, rather than indicating the superiority of a specific treatment sequence. Prospective studies with longer follow-up are warranted. Plain Language Summary: Hepatocellular carcinoma (HCC) is a common type of liver cancer, and many patients are not suitable for surgery at diagnosis. Transarterial radioembolization (TARE) is a locoregional treatment that delivers radiation directly to liver tumors and is increasingly used together with systemic therapies such as immunotherapy and targeted drugs. However, it is still unclear whether treatments given before TARE influence patient outcomes in real‑world practice. In this retrospective study, we analyzed 71 patients with HCC who received TARE at a single center. Patients were divided into two groups: those who had received systemic therapy before TARE and those who underwent TARE as their initial major treatment. We evaluated tumor response and survival outcomes starting from the time of TARE. We found that patients who received TARE as the initial treatment had better tumor response and longer progression‑free survival than those who had received systemic therapy before TARE. However, overall survival was similar between the two groups during the current follow‑up period. In addition, patients with a lower neutrophil‑to‑lymphocyte ratio, a blood‑based marker reflecting immune status, tended to have better outcomes after TARE. These findings suggest that previous treatment exposure and baseline immune status may influence outcomes after TARE, rather than indicating that one treatment sequence is definitively superior. Further prospective studies with longer follow‑up are needed to confirm these results and guide treatment planning for patients with HCC. Keywords: hepatocellular carcinoma, HCC, transarterial radioembolization, TARE, immune checkpoint inhibitors, ICIs, treatment exposure, neutrophil‑to‑lymphocyte ratio, NLR