Single-Fraction SABR Yields Comparable Overall Survival to Multi-Fraction SABR for Patients With Lung Oligometastases

Shankar Siva, PhD

A final survival analysis found no significant differences in patient survival outcomes between single or multifraction stereotactic ablative body radiotherapy (SABR) to treat oligometastases to the lung, according to findings from the Trans Tasman Radiation Oncology Group (TROG) /Australasian Lung Cancer Trials Group (ALTG) 13.001 trial (NCT01965223), which were published in the Journal of Clinical Oncology.

The median follow-up was 5.4 years; at which point, the estimated 3-year overall survival (OS) was 70% (95% CI, 59%-78%) and the estimated 5-year OS was 51% (95% CI, 39%-61%). No significant differences in OS were identified between patients who received multi- or single-fraction SABR (HR, 1.1; 95% CI, 0.6-2.0; P = .81).

The estimated 3- and 5-year disease-free survival (DFS) rates were 24% (95% CI, 16%-33%) and 20% (95% CI, 13%-29%), respectively. The rates of modified DFS (mDFS), which was defined as any progression not addressable by local therapy, or death, were 39% (95% CI, 29%-49%) and 34% (95% CI, 24%-44%), respectively. No significant differences were seen in either fractionation schedule in terms of DFS (HR, 1.0; 95% CI, 0.6-1.6; P = .92) or mDFS (HR, 1.0; 95% CI, 0.6-1.8; P = .90).

“This final long-term update to the SAFRON II trial is concordant with the initially published outcomes and the fact that there is no difference in clinical outcomes between single- and multifraction SABR for pulmonary oligometastases,” Shankar Siva, PhD, radiation oncologist at the Peter MacCallum Cancer Centre and associate professor at the University of Melbourne, and co-investigators, wrote in the study.

Previous reports demonstrated that, in a population of 90 patients, there were no differences in safety, efficacy, systemic immunogenicity, or survival, between single or multifraction SABR. Single-fraction SABR was determined to be the most cost-effective option as well; single-fraction treatment was determined to cost $1,194 less Australian dollars than multifraction SABR per patient. In the short term, the within-trial incremental cost-effectiveness ratio (ICER) was $15,821 Australian dollars/quality adjusted life-years (QALY). Over a 10-year span, the ICER was $23,265 Australian dollars/QALY.

Safety, which has been reported previously, was the primary end point. OS, DFS, and mDFS represented the long-term clinical outcomes.

The TROG 13.01/ALTG 13.001 SAFRON II study enrolled patients from 13 different institutions across Australia and New Zealand. Patients who participated had between 1 to 3 oligometastases to the lung, stemming from any nonhematologic structures. The oligometastases had to be located away from central structures. Tumor sizes could not exceed 5 cm.

All enrolled patients were 18 years or older, had an ECOG performance status of either 0 or 1, and their primary or extrathoracic diseases had been controlled with local therapy. Patients who were randomly assigned to receive single-fraction radiation received 28 GY. Those assigned to the multifraction arm received a total dose of 48 Gy in 4 daily 12-Gy fractions delivered over 2 weeks.

During the study, 69 patients progressed. Forty-six percent of patients did not receive systemic therapy on their first progression, at the discretion of the tumor board. For 29 of these patients, an additional course of local therapy was administered. Nine cases of first relapse were extrathoracic, and were thus treated with metastasis-directed therapy. Among the 23 cases of intrathoracic relapse, 3 patients (13%) did not undergo local therapy.

“As a meaningful proportion (one third) of patients observed were disease-free in the long term without the receipt of costly systemic therapy known to affect quality of life, we suggest that the strategy of SABR alone should be considered in selected patients,” study authors concluded.

Reference

Siva S, Sakyanun P, Mai T, et al. Long-term outcomes of TROG 13.01 SAFRON II randomized trial of single-versus multifraction stereotactic ablative body radiotherapy for pulmonary oligometastases. J Clin Oncol. 2023;41(19):3493-3498. doi:10.1200/JCO.23.00150