SIRT Combined with Targeted Therapy and Immunotherapy Achieves Sustained Complete Remission in Advanced...

Sorafenib was the standard systemic therapy for advanced hepatocellular carcinoma (HCC) for over a decade, but has largely been replaced by immunotherapy-based combinations. Current international guidelines recommend atezolizumab plus bevacizumab (A+T) or durvalumab plus tremelimumab (Dur/Tre) as first-line regimens for unresectable HCC. In the 5-year update of IMbrave150, A+T achieved an objective response rate (ORR) of 30% and a 5-year overall survival (OS) rate of 19%. In the Phase III HIMALAYA trial, Dur/Tre produced an ORR of 20%. By contrast, single-agent tyrosine kinase inhibitors (TKIs) such as sorafenib or lenvatinib yield a median OS of only 10-14 months. Median OS with locoregional therapies alone-transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC) and selective internal radiation therapy (SIRT)-range from 8 to 24 months, depending on baseline tumor burden and liver function. Even among responders to immune checkpoint inhibitors (ICIs), only 40-50% maintain durable responses; meanwhile, patients may also experience adverse events of varying severity, highlighting a substantial unmet need. Early-phase studies suggest that combining SIRT with systemic therapy can increase ORR to 40-60% while keeping grade 3-4 toxicities below 15%. Therefore, beyond survival, health-related quality of life (HRQOL) and treatment burden should be incorporated as key endpoints to evaluate the real-world trade-off between disease control and treatment burden.

This case indicates that, even with traditional relative contraindications, such as a high lung-shunt fraction (LSF) and low tumor-absorbed dose⁠ (TAD), SIRT may still serve as an "antigen-release platform", providing a foundation for sequential targeted therapy and immunotherapy, enabling deep remission in advanced HCC and creating conditions to maintain or improve HRQOL.