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

Abstract

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(s): To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases. Design, Setting, and Participant(s): 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 cm from 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. Intervention(s): 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 outcome was 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). Result(s): 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. Trial Registration: ClinicalTrials.gov Identifier: NCT01965223.Copyright © 2021 American Medical Association. All rights reserved.