title: Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases.
abstract: BACKGROUND
  In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection.
  
  
  METHODS
  Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed.
  
  
  RESULTS
  Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity.
  
  
  CONCLUSIONS
  NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois. Electronic address: hal-hallaq@radonc.uchicago.edu.
authors.forename: Hania A
authors.initials: HA
authors.lastname: Al-Hallaq
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Steven
authors.initials: S
authors.lastname: Chmura
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Salama
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.affiliation: Department of Radiation Oncology, Washington University, St. Louis, Missouri.
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Robinson
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pisansky
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado, Denver, Colorado.
authors.forename: Virginia
authors.initials: V
authors.lastname: Borges
authors.affiliation: Imaging and Radiation Oncology Core Group (IROC) Houston, MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lowenstein
authors.affiliation: Imaging and Radiation Oncology Core (IROC) Philadelphia RT, Philadelphia, Pennsylvania.
authors.forename: Susan
authors.initials: S
authors.lastname: McNulty
authors.affiliation: Imaging and Radiation Oncology Core (IROC) Philadelphia RT, Philadelphia, Pennsylvania.
authors.forename: James M
authors.initials: JM
authors.lastname: Galvin
authors.affiliation: Imaging and Radiation Oncology Core Group (IROC) Houston, MD Anderson Cancer Center, Houston, Texas.
authors.forename: David S
authors.initials: DS
authors.lastname: Followill
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern/Simmons Cancer Center, Dallas, Texas.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Timmerman
authors.affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, Ohio.
authors.forename: Julia R
authors.initials: JR
authors.lastname: White
authors.affiliation: Imaging and Radiation Oncology Core (IROC) Philadelphia RT, Philadelphia, Pennsylvania; Department of Radiation Oncology, The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Martha M
authors.initials: MM
authors.lastname: Matuszak
mesh_terms: D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy* / Q000556:secondary; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D054547:National Cancer Institute (U.S.); D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000473:pathology; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D014481:United States