Outcomes of SBRT to liver and portal vein tumor thrombus followed by immunotherapy or lenvatinib in BCLC-C hepatocellular carcinoma: A retrospective cohort study.

508 Background: Advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) poses a major therapeutic challenge due to aggressive biology and limited options. Systemic therapies like TKIs and immune checkpoint inhibitors offer clinical benefit, but their efficacy may improve with local tumor control. Following RTOG 1112, SBRT has gained relevance in managing BCLC-C patients. This study evaluates outcomes of SBRT to liver and PVTT followed by systemic therapy in a real-world cohort. Methods: We retrospectively analyzed 45 BCLC-C HCC patients treated at our center. All received SBRT to the primary liver lesion; selected cases received additional SBRT to PVTT based on thrombus extent and liver function. Post-SBRT, patients received either Lenvatinib or immunotherapy (monotherapy or combination). Primary endpoints: Overall survival (OS) and progression-free survival (PFS), defined from SBRT completion to death/progression or last follow-up. Secondary endpoint: Objective response rate (ORR) per RECIST criteria. Results: Median age was 59 years (range: 34–85); 91% were male. Macrovascular invasion was present in 78%. Median SBRT dose was 45 Gy (range: 30–60 Gy). Patients with Child-Pugh > B8 or residual liver volume <700 cc were excluded. Median follow-up: 22 months (95% CI: 13.7–30.2). Median OS: 12 months (95% CI: 4.6–19.3). Median PFS: 9 months (95% CI: 2.7–15.2). Systemic therapy post-SBRT: 13.4% received immunotherapy; 75.6% received TKIs. Surgical outcomes: 2 patients underwent liver transplantation; 1 underwent hepatectomy. Disease progression: 84.4% had no progression at data cutoff; 15.6% had distant progression. Radiologic response: 28.9% achieved complete response; 11.1% had partial response. ORR: Among 25 evaluable patients, ORR was 72%. Conclusions: In this cohort, SBRT combined with systemic therapy resulted in durable local responses and encouraging survival outcomes, with nearly half of the patients surviving one year. The observed improvement in median PFS compared to historical data suggests a potential synergistic effect of local and systemic therapies. In selected patients, combining SBRT with immunotherapy may offer a pathway to sustained disease control and increased eligibility for curative interventions such as liver transplantation. Further prospective studies are warranted to validate these findings and optimize treatment sequencing.