Phase 3 Multi-Center, Prospective, Randomized Trial Comparing Single-Dose 24 Gy Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Cancer

Purpose This prospective phase 3 randomized trial was designed to test whether ultra high single-dose radiation therapy (24 Gy SDRT) improves local control of oligometastatic lesions compared to a standard hypofractionated stereotactic body radiation therapy regimen (3 × 9 Gy SBRT). The secondary endpoint was to assess the associated toxicity and the impact of ablation on clinical patterns of metastatic progression. Methods and Materials Between November 2010 and September 2015, 117 patients with 154 oligometastatic lesions (≤5/patient) were randomized in a 1:1 ratio to receive 24 Gy SDRT or 3 × 9 Gy SBRT. Local control within the irradiated field and the state of metastatic spread were assessed by periodic whole-body positron emission tomography/computed tomography and/or magnetic resonance imaging. Median follow-up was 52 months. Results A total of 59 patients with 77 lesions were randomized to 24 Gy SDRT and 58 patients with 77 lesions to 3 × 9 Gy SBRT. The cumulative incidence of local recurrence for SDRT-treated lesions was 2.7% (95% confidence interval [CI], 0%-6.5%) and 5.8% (95% CI, 0.2%-11.5%) at years 2 and 3, respectively, compared with 9.1% (95% CI, 2.6%-15.6%) and 22% (95% CI, 11.9%-32.1%) for SBRT-treated lesions (P = .0048). The 2- and 3-year cumulative incidences of distant metastatic progression in the SDRT patients were 5.3% (95% CI, 0%-11.1%), compared with 10.7% (95% CI, 2.5%-18.8%) and 22.5% (95% CI, 11.1%-33.9%), respectively, for the SBRT patients (P = .010). No differences in toxicity were observed. Conclusions The study confirms SDRT as a superior ablative treatment, indicating that effective ablation of oligometastatic lesions is associated with significant mitigation of distant metastatic progression.