Stereotactic Body Radiation Therapy Combined With Immune Checkpoint Inhibitors in Unresectable Hepatocellular...

In locally advanced hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICI) are the frontline regimen, but the benefit of stereotactic body radiation (SBRT) in combination is unclear. Given randomized evidence for survival benefit with SBRT plus sorafenib, we performed a systematic review and meta-analysis to assess whether adding SBRT improves survival and response outcomes with acceptable toxicity.

Per PRISMA guidelines, we reviewed studies published from 2020 onward evaluating adults with intermediate or advanced HCC (BCLC B/C) treated with SBRT plus ICI. Eligible studies included phase II-III RCTs, prospective cohorts, prospective single-arm studies, and retrospective comparative cohorts (≥20 patients with confounding adjustment). Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and grade 3+ toxicity. A single-arm meta-analysis was performed using the REML method; logit transformation was applied for proportions, and heterogeneity was assessed through I 2 and Q-test.

Of 1120 screened studies, 6 (258 patients) met the inclusion criteria. Pooled median OS was 22.7 months (95% CI: 17.4-29.5; I2 =68.5%). Pooled median PFS was 7.9 months (95% CI: 5.6-11.2; I2 =92.1%). DCR was 93.4% (95% CI: 56.5-99.4%) and ORR was 56.3% (95% CI: 38-73%). Grade ≥3 toxicity occurred in 17.5% of patients (95% CI: 12.9-23.3%; I2 =0%).

SBRT combined with ICI demonstrates encouraging survival and response outcomes with manageable toxicity in unresectable HCC. Prospective randomized trials are needed to confirm efficacy and define optimal treatment algorithms.