Surgery and tile-based radiation therapy versus surgery and stereotactic radiation for newly diagnosed brain metastases (ROADS): a randomized, open-label, phase 3 trial

PURPOSE: Post-operative stereotactic radiation (SRT) is the standard-of-care for resected brain metastases. Implantation of cesium-131 collagen tiles (tile-based radiation therapy, TBRT) initiates focal radiation immediately after resection, potentially offering therapeutic and logistical advantages. ROADS: a randomized, open-label, non-inferiority, phase 3 trial (NCT04365374) compared the safety and efficacy of resection with TBRT (R+TBRT) to resection with SRT (R+SRT) for patients with a newly diagnosed brain metastasis indicated for surgical resection. PATIENTS AND METHODS: Across 32 United States centers, patients were pre-operatively randomized 1:1 to resection R+TBRT or R+SRT. Any non-resected brain metastases received SRT post-operatively. Co-primary outcomes were time-to-surgical bed recurrence (SBR) and surgical bed recurrence-free survival (SB-RFS). Outcomes were analyzed using Cox proportional hazards models with stratification factors as covariates. Multiplicity was controlled by hierarchical testing. Analyses used the pre-specified modified intent-to-treat (mITT) population (patients who underwent surgery, had pathologic confirmation of brain metastasis, and had follow-up information). RESULTS: From April 2021 through August 2025, 230 patients were randomized (115 per arm); 204 of whom (103 R+TBRT, 101 R+SRT) comprised the mITT population. Median follow-up was 12.9 months. Median time-to-SBR was not reached (R+TBRT) versus 17.4 months (R+SRT) (hazard ratio [HR]: 0.06; 95% confidence interval [CI]: 0.01-0.46; p=0.0070). SB-RFS was improved with R+TBRT, with a median of not reached versus 10.9 months (R+SRT) (HR: 0.48; 95% CI: 0.30-0.76; p=0.0021). Overall adverse events did not appear to differ: 83 patients (79.0%, 95% CI: 70.0-86.4) (R+TBRT) versus 67 patients (80.7%, 95% CI:70.6-88.6) (R+SRT). CONCLUSION: For patients with newly diagnosed brain metastases requiring resection, R+TBRT significantly improved SBR and SB-RFS, demonstrating both non-inferiority and superiority.