Efficacy and Safety of Sequential Radiotherapy and Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Single-Center PSM Retrospective Cohort Study
TL;DR
In this retrospective PSM cohort, RT followed by ICI was associated with improved PFS and tumor responses in advanced HCC, alongside manageable toxicity, suggesting potential value of RT as immune priming before ICI, though prospective validation is needed.
Abstract
Background The optimal administration sequence of immune checkpoint inhibitors (ICIs) and radiotherapy (RT) for advanced hepatocellular carcinoma (HCC) remains unclear. This study compared the efficacy and safety of ICIs administered before vs after RT in advanced HCC patients. Methods This single-center, retrospective cohort study employed propensity score matching (PSM). Patients with advanced HCC receiving sequential ICI-RT therapy (with or without concurrent targeted therapy) from January 2020 to December 2024 were divided into ICI+RT (ICI before RT, n=96) and RT+ICI (RT before ICI, n=100) groups, with treatment interval ≤14 days. Approximately half of patients in each group received concurrent targeted agents. Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). Results After 1:1 PSM, 77 paired patients were analyzed (median follow-up 19.4 months). The RT+ICI group demonstrated longer median PFS (7.8 vs 5.6 months, HR 1.551, 95% CI 1.038–2.317, p=0.031), higher ORR (74.0% vs 54.5%, p=0.019), and lower progressive disease rate as best response (0.0% vs 10.4%, p=0.006). Median OS showed numerical but non-significant improvement (14.1 vs 12.5 months, HR 1.112, 95% CI 0.746–1.657, p=0.600). Grade 3–4 thrombocytopenia was more frequent in RT+ICI (42.9% vs 20.8%, p=0.006). Longitudinal neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio changes suggested potential immune-priming effects of RT when administered before ICI. Conclusions In this retrospective PSM cohort, RT followed by ICI was associated with improved PFS and tumor responses in advanced HCC, alongside manageable toxicity. These findings suggest potential value of RT as immune priming before ICI, though prospective validation is needed given the observational nature and single-center design of this study.