Safety and Efficacy of Combining Metastasis-Directed Stereotactic Ablative Radiation Therapy with Tyrosine Kinase Inhibitors Versus Immune Checkpoint Inhibitors in Metastatic Hepatocellular Carcinoma.

[PURPOSE] Immune checkpoint inhibitors (ICIs) have become a standard therapy for metastatic hepatocellular carcinoma (HCC), often as an alternative to tyrosine kinase inhibitors (TKIs). However, safety data combining ICIs with stereotactic ablative radiotherapy (SABR) remain limited. We compared the safety and efficacy of SABR combined with ICIs versus TKIs in patients with extrahepatic metastatic HCC.

[MATERIALS AND METHODS] This single-center retrospective study included patients with HCC who received SABR for extrahepatic metastases combined with either TKIs or ICIs within 30 days of SABR between January 2010 and June 2024. Adverse events (AEs; CTCAE v5.0) and oncologic outcomes were evaluated using logistic regression and Cox models.

[RESULTS] Among 103 patients with 128 SABR-treated lesions, 72 patients (90 lesions) received SABR+TKI and 31 patients (38 lesions) received SABR+ICI. Acute AEs occurred only in the SABR+TKI group (8.9%), predominantly grade 1. Grade 3 late AEs were rare, occurring in one case in each group, while late AEs of lower grades were more frequent with SABR+ICI (any-grade: 57.9% vs. 25.6%, p<0.001; grade ≥2: 23.7% vs. 8.9%, p=0.024). Multivariable analysis showed borderline increased risk of grade ≥2 late AEs with SABR+ICI (p=0.052). One-year local control, progression-free survival, and overall survival were 76.6%, 35.3%, and 72.3% respectively, with no significant differences between groups.

[CONCLUSION] Metastasis-directed SABR combined with either TKIs or ICIs was generally well tolerated in patients with extrahepatic metastatic HCC, with rare grade 3 late AEs; grade ≥2 late AEs were more frequent with SABR plus ICIs, warranting prospective evaluation.