Abstract
BACKGROUND: Combination immunotherapy, particularly the STRIDE regimen (durvalumab plus tremelimumab), is recommended as first-line treatment for advanced hepatocellular carcinoma (HCC). Cytokine release syndrome (CRS), while rare, can be a life-threatening adverse event associated with immune checkpoint inhibitors (ICIs). The relationship between CRS and antitumor activity remains unclear; however, some studies suggest that the occurrence of immune-related adverse events (irAEs) may be indicative of enhanced immune activation. We report a case in which severe CRS following ICI therapy led to marked tumor shrinkage and enabled conversion surgery. CASE PRESENTATION: An 85-year-old woman presented with a 100 mm HCC in the right hepatic lobe with intrahepatic metastases, initially deemed unresectable. She received the STRIDE regimen and developed Grade 3 CRS with fever, hypotension, and multi-organ dysfunction. Corticosteroid therapy led to rapid clinical improvement. Three months post-treatment, imaging revealed tumor regression (from 100 mm to 60 mm) and significant decline in tumor markers (AFP 1550-110 ng/mL; PIVKA-2 32,600 to 79 AU/mL). Extended anterior sectionectomy was performed, with histopathology showing 90% tumor necrosis. The postoperative course was uneventful, and the patient was discharged on postoperative day 16. CONCLUSION: CRS is a potentially severe irAE that may also signal favorable immune activation. Early recognition and appropriate management of CRS are essential, and in select cases, ICI-induced CRS may facilitate curative conversion surgery in advanced HCC.