PMID- 34455431 OWN - NLM STAT- MEDLINE DCOM- 20220311 LR - 20220830 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 7 IP - 10 DP - 2021 Oct 1 TI - 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. PG - 1476-1485 LID - 10.1001/jamaoncol.2021.2939 [doi] AB - 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. FAU - Siva, Shankar AU - Siva S AD - Department of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia. AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. FAU - Bressel, Mathias AU - Bressel M AD - Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Victoria, Australia. FAU - Mai, Tao AU - Mai T AD - Radiation Oncology Centre, Princess Alexandra Hospital, Queensland, Australia. FAU - Le, Hien AU - Le H AD - Department of Radiation Oncology, Royal Adelaide Hospital, South Australia, Australia. FAU - Vinod, Shalini AU - Vinod S AD - Cancer Therapy Centre, Liverpool Hospital, New South Wales, Australia. FAU - de Silva, Harini AU - de Silva H AD - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. FAU - Macdonald, Sean AU - Macdonald S AD - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. FAU - Skala, Marketa AU - Skala M AD - Royal Hobart Hospital, Tasmania, Australia. FAU - Hardcastle, Nicholas AU - Hardcastle N AD - Department of Physical Sciences, Peter MacCallum Cancer Centre, Victoria, Australia. FAU - Rezo, Angela AU - Rezo A AD - Canberra Hospital, Garran, Australian Capital Territory, Australia. FAU - Pryor, David AU - Pryor D AD - Radiation Oncology Centre, Princess Alexandra Hospital, Queensland, Australia. FAU - Gill, Suki AU - Gill S AD - Sir Charles Gairdner Hospital, Western Australia, Australia. FAU - Higgs, Braden AU - Higgs B AD - Department of Radiation Oncology, Royal Adelaide Hospital, South Australia, Australia. FAU - Wagenfuehr, Kassandra AU - Wagenfuehr K AD - Trans Tasman Radiation Oncology Group (TROG) Cancer Research, New South Wales, Australia. FAU - Montgomery, Rebecca AU - Montgomery R AD - Trans Tasman Radiation Oncology Group (TROG) Cancer Research, New South Wales, Australia. FAU - Awad, Raef AU - Awad R AD - Royal Hobart Hospital, Tasmania, Australia. FAU - Chesson, Brent AU - Chesson B AD - Department of Radiation Therapy, Peter MacCallum Cancer Centre, Victoria, Australia. FAU - Eade, Thomas AU - Eade T AD - Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia. FAU - Wong, Wenchang AU - Wong W AD - Department of Radiation Oncology, Prince of Wales Hospital, New South Wales, Australia. FAU - Sasso, Giuseppe AU - Sasso G AD - Radiation Oncology Department, Auckland City Hospital, New Zealand. FAU - De Abreu Lourenco, Richard AU - De Abreu Lourenco R AD - Centre for Health Economics Research and Evaluation, University of Technology Sydney, New South Wales, Australia. FAU - Kron, Tomas AU - Kron T AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. AD - Radiation Oncology Centre, Princess Alexandra Hospital, Queensland, Australia. FAU - Ball, David AU - Ball D AD - Department of Radiation Oncology, Peter MacCallum Cancer Centre, Victoria, Australia. AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. FAU - Neeson, Paul AU - Neeson P AD - Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia. AD - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. CN - Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung (SAFRON) II Study Investigators LA - eng SI - ClinicalTrials.gov/NCT01965223 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 SB - IM CIN - JAMA Oncol. 2021 Oct 1;7(10):1485-1486. PMID: 34455429 MH - Child MH - Humans MH - Lung MH - Male MH - *Neoplasms/etiology MH - Progression-Free Survival MH - Proportional Hazards Models MH - *Radiosurgery/adverse effects/methods MH - Treatment Outcome PMC - PMC8404145 COIS- Conflict of Interest Disclosures: Dr Siva reported receiving grants from Cancer Australia Government and Varian Medical Systems during the conduct of the study and grants from Bayer Pharmaceuticals and Varian Industries, honoraria from Reflexion and AstraZeneca, and personal fees for travel expenses from AstraZeneca outside the submitted work. Dr Hardcastle reported receiving grants from Cancer Australia and Varian Medical Systems during the conduct of the study and grants from Varian Medical Systems outside the submitted work; in addition, Dr Hardcastle had a patent for US20130004034, a patent for WO2012123861, and a patent for WO2012069965 relevant to radiation therapy in general. Dr Pryor reported receiving personal fees from Roche outside the submitted work. Dr Chesson reported receiving grants from Cancer Australia and Varian Medical Systems. Dr Sasso reported receiving grants from Auckland Medical Research Foundation during the conduct of the study. Dr De Abreu Lourenco reported receiving grants from Cancer Australia during the conduct of the study. Dr Kron reported receiving grants from Cancer Australia during the conduct of the study and having an academic appointment at the University of Wollongong outside the submitted work. Dr Ball reported receiving personal fees from AstraZeneca outside the submitted work. Dr Neeson reported receiving grants from Cancer Australia Government and Varian Medical Systems during the conduct of the study and grants from BMS, Roche Genentech, Compugen, Allergan, CRISPR, and Merck Sharp & Dohme outside the submitted work. No other disclosures were reported. FIR - Bettington, Catherine IR - Bettington C FIR - Cook, Olivia IR - Cook O FIR - Foote, Matthew IR - Foote M FIR - Gowda, Raghu IR - Gowda R FIR - Haas, Marion IR - Haas M FIR - Haynes, Nicole M IR - Haynes NM FIR - Hilder, Bronwyn IR - Hilder B FIR - Lao, Louis IR - Lao L FIR - Lim, Adeline IR - Lim A FIR - Ludbrook, Jane IR - Ludbrook J FIR - Jansen, Therease IR - Jansen T FIR - MacManus, Michael IR - MacManus M FIR - McCullough, Susan A IR - McCullough SA FIR - Moore, Alisha IR - Moore A FIR - Ritchie, David IR - Ritchie D FIR - Shaw, Mark IR - Shaw M FIR - Sia, Joseph IR - Sia J FIR - Syed, Farhan IR - Syed F FIR - Tang, Colin IR - Tang C FIR - Trapani, Joseph IR - Trapani J EDAT- 2021/08/30 06:00 MHDA- 2022/03/12 06:00 PMCR- 2022/08/29 CRDT- 2021/08/29 21:04 PHST- 2021/08/30 06:00 [pubmed] PHST- 2022/03/12 06:00 [medline] PHST- 2021/08/29 21:04 [entrez] PHST- 2022/08/29 00:00 [pmc-release] AID - 2783660 [pii] AID - coi210047 [pii] AID - 10.1001/jamaoncol.2021.2939 [doi] PST - ppublish SO - JAMA Oncol. 2021 Oct 1;7(10):1476-1485. doi: 10.1001/jamaoncol.2021.2939.