Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II) The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial

IMPORTANCE Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases. OBJECTIVE To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases. DESIGN, SETTING, AND PARTICIPANTS This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cmfrom any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years. INTERVENTIONS Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis. MAIN OUTCOMES AND MEASURES The main outcomewas grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale). RESULTS Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P =.13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P =.44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P >.99). There were no significant differences observed in patient-reported outcomes. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies.