In the phase II SAFRON II study reported in JAMA Oncology, Shankar Siva, PhD, MBBS, FRANZCR, and colleagues found no significant differences in safety or efficacy between single-fraction vs multifraction stereotactic ablative body radiotherapy (SABR) for the treatment of pulmonary oligometastases.
Shankar Siva, PhD, MBBS, FRANZCR
Study Details
The open-label multicenter trial included 87 patients with one to three lung oligometastases ≤ 5 cm from any nonhematologic malignant tumors located away from the central airways. Patients were randomly assigned between January 2015 and December 2018 to receive SABR with a single fraction of 28 Gy (n = 44) or four fractions of 12 Gy (n = 43) to each oligometastasis. Patients had to have all primary and extrathoracic disease controlled with local therapy.
The primary endpoint was grade ≥ 3 treatment-related adverse events occurring within 1 year of SABR. Minimum patient follow-up was 2 years.
Adverse Events
The 87 patients were treated for a total of 133 pulmonary oligometastases. Median follow-up was 36.5 months (interquartile range = 24.8–43.9 months).
Among 38 patients in each group who completed 1 year of follow-up and were eligible for the primary endpoint analysis, grade ≥ 3 treatment-related adverse events occurred in one patient (3%, 80% confidence interval [CI] = 0%–10%) in the multifraction group vs two patients (5%, 80% CI = 1%–13%) in the single-fraction group (P = .37). A grade 5 adverse event occurred in one patient in the multifraction group, consisting of hypoxia and radiation pneumonitis within 3 months of SABR.
Any-grade radiation dermatitis (7 vs 0 patients) and esophagitis (8 vs 1 patient) were more common in the multifraction group.
Efficacy Outcomes
KEY POINTS
- No significant difference in grade ≥ 3 treatment-related adverse events was observed between the multifraction vs single-fraction groups.
- No significant differences between groups were observed for freedom from local failure, overall survival, or disease-free survival.
No significant differences were found between the multifraction vs single-fraction groups 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). Median duration of freedom from local failure was not reached in either group, with estimated 1- and 3-year rates of 95% vs 93% and 80% vs 64%.
Median overall survival was not reached in either group, with estimated 1- and 3-year rates of 93% vs 95% and 67% vs 81%. Median disease-free survival was 13.2 months vs 14.3 months.
The investigators concluded, “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 endpoints, could be chosen to escalate to future studies.”
Dr. Siva, of Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by Cancer Australia and Auckland Medical Research Foundation. For full disclosures of the study authors, visit jamanetwork.com.
