PMID- 33885704
OWN - NLM
STAT- MEDLINE
DCOM- 20220311
LR  - 20230317
IS  - 2374-2445 (Electronic)
IS  - 2374-2437 (Print)
IS  - 2374-2437 (Linking)
VI  - 7
IP  - 6
DP  - 2021 Jun 1
TI  - Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of 
      Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial.
PG  - 845-852
LID - 10.1001/jamaoncol.2021.0687 [doi]
AB  - IMPORTANCE: Stereotactic body radiotherapy (SBRT) for oligometastases is 
      hypothesized to improve survival and is increasingly used. Little evidence 
      supports its safe use to treat patients with multiple metastases. OBJECTIVE: To 
      establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 
      metastases in close proximity to each other. DESIGN, SETTING, AND PARTICIPANTS: 
      This phase 1 trial opened on August 4, 2014, and closed to accrual on March 20, 
      2018. Metastases to 7 anatomic locations were included: bone/osseous (BO), 
      spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic 
      (AP), mediastinal/cervical lymph node (MC), and liver (L). Six patients could be 
      enrolled per anatomic site. The setting was a consortium of North American 
      academic and community practice cancer centers participating in NRG Oncology 
      trials. Patients with breast, prostate, or non-small cell lung cancer with 3 to 4 
      metastases or 2 metastases in close proximity (</=5 cm) amenable to SBRT were 
      eligible for this phase 1 study. Statistical analyses were performed from 
      December 31, 2017, to September 19, 2019. INTERVENTIONS: The starting dose was 50 
      Gy in 5 fractions (CL, MC), 45 Gy in 3 fractions (PL, AP, L), and 30 Gy in 3 
      fractions (BO, SP). MAIN OUTCOMES AND MEASURES: The primary end point was 
      dose-limiting toxicity (DLT) defined by the Common Terminology Criteria for 
      Adverse Events, version 4.0, as specific adverse events (AEs) of grades 3 to 5 
      (definite or probable per the protocol DLT definition) related to SBRT within 180 
      days of treatment. Dose levels were considered safe if DLTs were observed in no 
      more than 1 of 6 patients per location; otherwise, the dose at that location 
      would be de-escalated. RESULTS: A total of 42 patients enrolled, 39 were 
      eligible, and 35 (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White 
      patients [85.7%]) were evaluable for DLT. Twelve patients (34.3%) had breast 
      cancer, 10 (28.6%) had non-small cell lung cancer, and 13 (37.1%) had prostate 
      cancer; there was a median of 3 metastases treated per patient. Median survival 
      was not reached. No protocol-defined DLTs were observed. When examining all AEs, 
      8 instances of grade 3 AEs, most likely related to protocol therapy, occurred 
      approximately 125 to 556 days from SBRT initiation in 7 patients. CONCLUSIONS AND 
      RELEVANCE: This phase 1 trial demonstrated the safety of SBRT for patients with 3 
      to 4 metastases or 2 metastases in close proximity. There were no 
      treatment-related deaths. Late grade 3 AEs demonstrate the need for extended 
      follow-up in long-surviving patients with oligometastatic disease. Treatment with 
      SBRT for multiple metastases has been expanded into multiple ongoing randomized 
      phase 2/3 National Cancer Institute-sponsored trials (NRG-BR002, NRG-LU002). 
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02206334.
FAU - Chmura, Steve
AU  - Chmura S
AD  - University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
FAU - Winter, Kathryn A
AU  - Winter KA
AD  - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
FAU - Robinson, Clifford
AU  - Robinson C
AD  - Department of Radiation Oncology, Washington University in St Louis, St Louis, 
      Missouri.
FAU - Pisansky, Thomas M
AU  - Pisansky TM
AD  - Department of Medicine-Medical Oncology, Mayo Clinic, Rochester, Minnesota.
FAU - Borges, Virginia
AU  - Borges V
AD  - University of Colorado-Anschutz Medical Center, Aurora.
FAU - Al-Hallaq, Hania
AU  - Al-Hallaq H
AD  - University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
FAU - Matuszak, Martha
AU  - Matuszak M
AD  - Department of Radiation Oncology, University of Michigan, Ann Arbor.
FAU - Park, Sean S
AU  - Park SS
AD  - Department of Medicine-Medical Oncology, Mayo Clinic, Rochester, Minnesota.
FAU - Yi, Sun
AU  - Yi S
AD  - Department of Radiation Oncology, University of Arizona Medical Center - 
      University Campus, Tucson.
FAU - Hasan, Yasmin
AU  - Hasan Y
AD  - University of Chicago Comprehensive Cancer Center, Chicago, Illinois.
FAU - Bazan, Jose
AU  - Bazan J
AD  - Ohio State University Comprehensive Cancer Center, Columbus.
FAU - Wong, Philip
AU  - Wong P
AD  - Centre Hospitalier de L'Universite de Montreal, Hotel Dieu de Montreal, Montreal, 
      Quebec, Canada.
FAU - Yoon, Harold A
AU  - Yoon HA
AD  - Heartland Cancer Research National Cancer Institute Community Oncology Research 
      Program, Decatur, Illinois.
FAU - Horton, Janet
AU  - Horton J
AD  - Department of Radiation Oncology, Duke University Medical Center, Durham, North 
      Carolina.
FAU - Gan, Gregory
AU  - Gan G
AD  - New Mexico Minority Underserved National Cancer Institute Community Oncology 
      Research Program, Albuquerque.
FAU - Milano, Michael T
AU  - Milano MT
AD  - Department of Radiation Oncology, University of Rochester, Rochester, New York.
FAU - Sigurdson, Elin Ruth
AU  - Sigurdson ER
AD  - Fox Chase Cancer Center, Philadelphia, Pennsylvania.
FAU - Moughan, Jennifer
AU  - Moughan J
AD  - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
FAU - Salama, Joseph K
AU  - Salama JK
AD  - Department of Radiation Oncology, Duke University Medical Center, Durham, North 
      Carolina.
FAU - White, Julia
AU  - White J
AD  - Ohio State University Comprehensive Cancer Center, Columbus.
LA  - eng
SI  - ClinicalTrials.gov/NCT02206334
GR  - U10 CA180868/CA/NCI NIH HHS/United States
GR  - UG1 CA189867/CA/NCI NIH HHS/United States
GR  - UG1 CA233324/CA/NCI NIH HHS/United States
GR  - P20 GM130423/GM/NIGMS NIH HHS/United States
GR  - U24 CA180803/CA/NCI NIH HHS/United States
GR  - U10 CA180822/CA/NCI NIH HHS/United States
GR  - P30 CA014236/CA/NCI NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - JAMA Oncol
JT  - JAMA oncology
JID - 101652861
SB  - IM
CIN - JAMA Oncol. 2021 Jun 1;7(6):852. PMID: 33885756
MH  - *Breast Neoplasms/pathology
MH  - *Carcinoma, Non-Small-Cell Lung/pathology
MH  - Female
MH  - Humans
MH  - *Lung Neoplasms/pathology
MH  - Male
MH  - *Prostatic Neoplasms/pathology
MH  - *Radiosurgery/adverse effects/methods
PMC - PMC8063134
COIS- Conflict of Interest Disclosures: Dr Winter reported receiving grants from the 
      National Cancer Institute (NCI) NRG Oncology Statistics and Data Management 
      Center during the conduct of the study. Dr Robinson reported receiving grants and 
      personal fees from Varian Medical Systems, grants from Elekta, and equity from 
      Radialogica outside the submitted work. Dr Al-Hallaq reported receiving grants 
      from Varian Medical Systems and royalties from patents licensed through the 
      university from the University of Chicago outside the submitted work. Dr Chmura 
      reported receiving personal fees from RefleXion, a close relative receiving a 
      salary from Astellas Pharma, and grants from Merck, Bristol Myers Squibb, and 
      Emanuel Merck, Darmstadt Serono outside the submitted work. Dr Horton reported 
      that as of October 2018, she moved from Duke University to employment with G1 
      Therapeutics. Dr Matuszak reported receiving grants and consulting fees from 
      Varian Medical Systems outside the submitted work. Dr Milano reported receiving 
      personal fees from Galera Therapeutics, Wolters Kluwer, and AstraZeneca outside 
      the submitted work. Dr Wong reported receiving grants from Bristol Myers Squibb 
      and AstraZeneca, NexPlasmaGen, and Instadesign, and being a major shareholder of 
      MISO Chip Inc outside the submitted work. Dr Yi reported receiving grants and 
      nonfinancial support from Rowpar Pharmaceuticals outside the submitted work. Dr 
      Yoon reported receiving grants from NCI during the conduct of the study. No other 
      disclosures were reported.
EDAT- 2021/04/23 06:00
MHDA- 2022/03/12 06:00
PMCR- 2022/04/22
CRDT- 2021/04/22 12:18
PHST- 2021/04/23 06:00 [pubmed]
PHST- 2022/03/12 06:00 [medline]
PHST- 2021/04/22 12:18 [entrez]
PHST- 2022/04/22 00:00 [pmc-release]
AID - 2778658 [pii]
AID - coi210007 [pii]
AID - 10.1001/jamaoncol.2021.0687 [doi]
PST - ppublish
SO  - JAMA Oncol. 2021 Jun 1;7(6):845-852. doi: 10.1001/jamaoncol.2021.0687.