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Original Investigation
August 29, 2021

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

Author Affiliations
  • 1Department of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia
  • 2Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
  • 3Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victoria, Australia
  • 4Radiation Oncology Centre, Princess Alexandra Hospital, Queensland, Australia
  • 5Department of Radiation Oncology, Royal Adelaide Hospital, South Australia, Australia
  • 6Cancer Therapy Centre, Liverpool Hospital, New South Wales, Australia
  • 7Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  • 8Royal Hobart Hospital, Tasmania, Australia
  • 9Department of Physical Sciences, Peter MacCallum Cancer Centre, Victoria, Australia
  • 10Canberra Hospital, Garran, Australian Capital Territory, Australia
  • 11Sir Charles Gairdner Hospital, Western Australia, Australia
  • 12Trans Tasman Radiation Oncology Group (TROG) Cancer Research, New South Wales, Australia
  • 13Department of Radiation Therapy, Peter MacCallum Cancer Centre, Victoria, Australia
  • 14Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia
  • 15Department of Radiation Oncology, Prince of Wales Hospital, New South Wales, Australia
  • 16Radiation Oncology Department, Auckland City Hospital, New Zealand
  • 17Centre for Health Economics Research and Evaluation, University of Technology Sydney, New South Wales, Australia
JAMA Oncol. 2021;7(10):1476-1485. doi:10.1001/jamaoncol.2021.2939
Key Points

Question  Is single-fraction or multifraction stereotactic ablative body radiotherapy (SABR) optimal for the treatment of patients with 1 to 3 oligometastases to the lung?

Findings  In this phase 2 randomized clinical trial that included 90 patients, the primary end point of severe toxicity was no different in the single-fraction arm (5%) than in the multifraction arm (3%). The secondary end points of efficacy, survival, and quality of life were also not different between the study arms.

Meaning  Single-fraction SABR is of shorter duration and thus may be preferred from resource and patient perspectives.

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  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 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).

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.

Trial Registration  ClinicalTrials.gov Identifier: NCT01965223

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