Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II)

Abstract

for the Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung (SAFRON) II Study Investigators 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 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.INTERVENTIONS Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis. MAIN OUTCOMES AND MEASURESThe 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).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 RELEVANCEIn 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.

Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done

“…Nine studies met criteria for this analysis [10,11,16,[21][22][23][24][25][26]. Publication years ranged from 2003 to 2021.…”

“…The phase II SAFRON II trial randomized 87 patients with 133 pulmonary metastases to either 28 Gy in a single fraction or 48 Gy in four fractions [16]. No significant differences were found between the multi-and single-fraction arms for freedom from local failure (95% versus 93%, p = 0.13), OS (95% versus 93%, p = 0.44), or median disease-free survival (13.2 versus 14.3 months, p > 0.99) [16].…”

“…The lungs are the first site of distant metastatic disease for many malignant tumors. A randomized trial in pulmonary oligometastases suggested similar outcomes at 1 year post single-or multi-fraction SBRT [16].…”

Image-Guided Robotic Radiosurgery for the Treatment of Lung Metastases of Renal Cell Carcinoma—A Retrospective, Single Center Analysis

“…Interestingly, higher doses showed a trend towards better outcomes in this study [ 21 ]. Recent clinical trial data revealed that single-fraction SBRT is more effective than multi-fraction SBRT in pulmonary oligometastases [ 22 ]. This evidence supports the rationale for RRS treatment in the setting of renal cell carcinoma with pulmonary metastases.…”

Bibliometric Analysis of the Top-Cited Publications and Research Trends for Stereotactic Body Radiotherapy

“…A phase 3 randomized trial showed that the local recurrence rate of single-dose 24 Gy radiotherapy was lower than that 27 Gy SBRT in three fractions, with no significant difference in toxicity ( 25 ). However, the results of a phase 2 randomized trial (SAFRON II) published in August 2021 demonstrated that SABR with a single 28-Gy fraction and four fractions of 12 Gy for lung oligometastases yielded comparable outcomes ( 26 ).…”