Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial
David A. Palma,
Robert Olson,
Stephen Harrow,
Rohann J. M. Correa,
Famke Schneiders,
Cornelis J. A. Haasbeek,
George B. Rodrigues,
Michael Lock,
Brian P. Yaremko,
Glenn S. Bauman,
Belal Ahmad,
Devin Schellenberg,
Mitchell Liu,
Stewart Gaede,
Joanna Laba,
Liam Mulroy,
Sashendra Senthi,
Alexander V. Louie,
Anand Swaminath,
Anthony Chalmers,
Andrew Warner,
Ben J. Slotman,
Tanja D. de Gruijl,
Alison Allan,
Suresh Senan
Affiliations
David A. Palma
Department of Oncology Western University, London Health Sciences Centre
Robert Olson
Department of Radiation Oncology, British Columbia Cancer, Centre for the North
Stephen Harrow
Beatson West of Scotland Cancer Centre
Rohann J. M. Correa
Department of Oncology Western University, London Health Sciences Centre
Famke Schneiders
Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam
Cornelis J. A. Haasbeek
Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam
George B. Rodrigues
Department of Oncology Western University, London Health Sciences Centre
Michael Lock
Department of Oncology Western University, London Health Sciences Centre
Brian P. Yaremko
Department of Oncology Western University, London Health Sciences Centre
Glenn S. Bauman
Department of Oncology Western University, London Health Sciences Centre
Belal Ahmad
Department of Oncology Western University, London Health Sciences Centre
Devin Schellenberg
Department of Radiation Oncology, British Columbia Cancer, Centre for the North
Mitchell Liu
Department of Radiation Oncology, British Columbia Cancer, Centre for the North
Stewart Gaede
Department of Oncology Western University, London Health Sciences Centre
Joanna Laba
Department of Oncology Western University, London Health Sciences Centre
Liam Mulroy
Nova Scotia Cancer Centre
Sashendra Senthi
Alfred Health Radiation Oncology
Alexander V. Louie
Department of Radiation Oncology, Sunnybrook Cancer Centre
Anand Swaminath
Juravinski Cancer Centre
Anthony Chalmers
Institute of Cancer Sciences, University of Glasgow
Andrew Warner
Department of Oncology Western University, London Health Sciences Centre
Ben J. Slotman
Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam
Tanja D. de Gruijl
Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam
Alison Allan
Department of Oncology Western University, London Health Sciences Centre
Suresh Senan
Department of Radiation Oncology, Amsterdam UMC Vrije Universiteit Amsterdam Radiation Oncology, Cancer Center Amsterdam
Abstract Background Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1–3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4–10 metastatic cancer lesions. Methods One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. Discussion This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4–10 oligometastatic lesions. Trial registration Clinicaltrials.gov identifier: NCT03721341. Date of registration: October 26, 2018.
