title: Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study.
abstract: OBJECTIVE
  Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS).
  
  
  METHODS
  We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with ClinicalTrials.gov (clinicaltrials.gov identifier NCT01046123).
  
  
  RESULTS
  From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient.
  
  
  CONCLUSIONS
  For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.
authors.affiliation: Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: anichol@bccancer.bc.ca.
authors.forename: Alan
authors.initials: A
authors.lastname: Nichol
authors.affiliation: Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Roy
authors.initials: R
authors.lastname: Ma
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, BC Cancer Agency, Abbotsford Centre, Abbotsford, British Columbia, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Hsu
authors.affiliation: Department of Surveillance and Outcomes, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Lovedeep
authors.initials: L
authors.lastname: Gondara
authors.affiliation: Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hannah
authors.initials: H
authors.lastname: Carolan
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, BC Cancer Agency, Centre for the North, Prince George, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Olson
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia, Canada.
authors.forename: Devin
authors.initials: D
authors.lastname: Schellenberg
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, BC Cancer Agency, Sindi Ahluwalia Centre for the Southern Interior, Kelowna, British Columbia, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Germain
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Radiation Oncology, BC Cancer Agency, Fraser Valley Centre, Surrey, British Columbia, Canada.
authors.forename: Arthur
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Peacock
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Physics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Alanah
authors.initials: A
authors.lastname: Bergman
authors.affiliation: Department of Medical Physics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Vollans
authors.affiliation: Department of Radiation Therapy, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Rosemin
authors.initials: R
authors.lastname: Vellani
authors.affiliation: Department of Radiation Oncology, BC Cancer Agency, Vancouver Centre, Vancouver, British Columbia, Canada; University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: McKenzie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary* / Q000601:surgery*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000379:methods*; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D013788:Thalamus; D013997:Time Factors