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Abstract
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. An 85-year-old woman presented with a 100mm 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 100mm to 60mm) and significant decline in tumor markers (AFP 1550-110ng/mL; PIVKA-2 32,600 to 79AU/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. 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.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally and presents a significant public health challenge [1, 2]
We report an unresectable hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs) doublet, in which Cytokine release syndrome (CRS) developed
Early corticosteroid administration was associated with shortened survival, even when ICIs were continued. This suggests that while steroids effectively mitigate immune-related adverse events (irAEs), their timing may influence long-term oncologic outcomes. These findings align with the case reported here, where corticosteroid therapy for CRS led to rapid clinical improvement and did not appear to compromise tumor regression or subsequent conversion surgery
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally and presents a significant public health challenge [1, 2]. A Magnetic resonance imaging (MRI) showed a 100 mm tumor in the right hepatic lobe and two smaller intrahepatic metastases in segments 3 and 4 (Fig. 1A). The imaging showed narrowing of the middle hepatic vein (MHV) due to tumor compression and dilation of the posterior segmental bile duct (Fig. 1B). Three months following the initial treatment, which consisted of a single dose of therapy with no subsequent courses, imaging revealed significant tumor shrinkage from 100 mm to 60 mm. In addition no evidence of dilation was observed in the posterior segmental bile ducts, and two intrahepatic metastatic lesions in the left hepatic lobe had completely disappeared (Fig. 1C, 1D). Histopathological examination revealed that 90% of the lesions were necrotic, with lymphocyte and plasma cell infiltration, indicative of changes associated with ICI treatment (Fig. 3A).
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