Title : A prospective study of tislelizumab combined with radiotherapy in unresectable or recurrent advanced hepatocellular carcinoma: Efficacy and immunological safety analysis
Abstract:
Background: Radiotherapy (RT) can induce immunogenic cell death and enhance tumor antigen release and presentation, thereby augmenting the host anti-tumor immune response. The combination of PD-1 inhibitor tislelizumab with RT may produce synergistic effects and improve outcomes in advanced or recurrent hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and immunological safety of tislelizumab combined with RT in patients with unresectable or progressive recurrent HCC.
Methods: This was a single-center, single-arm, prospective clinical study. From March 2023 to March 2025, 32 patients with unresectable or recurrent progressive HCC were enrolled. All patients received local RT (30–50 Gy) combined with tislelizumab (200 mg every 3 weeks) administered concurrently or sequentially for at least one cycle. The primary endpoints were immune-related adverse events (irAEs) and treatment-related adverse events (TRAEs). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and duration of response (DOR).
Results: A total of 32 patients were enrolled, with a median age of 59 years (range 43–75); 28 were male and 4 were female. The clinical stages included IIIA (n=3), IIIB (n=17), and IVA (n=12), with 29 patients presenting with portal vein tumor thrombus (PVTT). The incidence of any-grade TRAEs was 96.9% (31/32), mainly fatigue (65.6%), decreased appetite (75.0%), hepatic dysfunction (87.5%), and hematologic toxicity (anemia 6.3%, thrombocytopenia 18.8%). Grade ≥3 TRAEs occurred in 15.9% of patients, with no treatment discontinuation or death due to adverse events. The incidence of irAEs was 96.9%, including hepatotoxicity (50.0%), endocrine disorders (31.2%), mild diarrhea/colitis (34.4%), and skin reactions (9.4%), with grade ≥3 irAEs in 21.9% of patients.
The overall response rate (ORR) was 37.5%, and the disease control rate (DCR) was 65.6%. The median PFS was 7.3 months, with a 6-month PFS rate of 47.1%. The 6-month OS rate was 86.7%, and the median OS had not yet been reached at data cutoff.
Conclusions: Tislelizumab combined with radiotherapy demonstrated promising efficacy and manageable immunological safety in patients with unresectable or recurrent advanced HCC. This combined approach provides a potential therapeutic option and warrants further validation in multicenter randomized controlled trials.
