title: A prospective phase II trial of fractionated stereotactic intensity modulated radiotherapy with or without surgery in the treatment of patients with 1 to 3 newly diagnosed symptomatic brain metastases.
abstract: BACKGROUND
  Several studies have demonstrated that omitting the routine use of adjuvant whole-brain radiation therapy for patients with newly diagnosed brain metastases may be a reasonable first-line strategy. Retrospective evidence suggests that fractionated stereotactic radiotherapy (fSRT) may have a lower level of toxicity with equivalent efficacy in comparison with radiosurgery.
  
  
  OBJECTIVE
  To study the phase II efficacy of using a focally directed treatment strategy for symptomatic brain metastases by the use of fSRT with or without surgery and omitting the routine use of adjuvant whole-brain radiation therapy.
  
  
  METHODS
  We used a Fleming single-stage design of 40 patients. Patients were eligible if they presented with 1 to 3 newly diagnosed symptomatic brain metastases, Karnofsky performance scale (KPS) greater than 60, and histological confirmation of primary disease. Patients underwent fSRT with the use of a dose of 30 Gy in 5 intensity-modulated fractions as primary or adjuvant treatment after surgical resection. The primary end point was the proportion of patients who experienced neurological death. Secondary end points were overall survival, time to KPS <70, and progression-free survival.
  
  
  RESULTS
  Of 40 patients accrued, 39 were eligible for analysis. The proportion of patients dying of neurological causes was 13% (5 patients), which includes 3 patients with an unknown cause of death. Median overall survival, time to KPS <70, and progression-free survival were 16 (95% confidence interval, 9-23), 14 (95% confidence interval, 7-20), and 11 (95% confidence interval, 4-21) months, respectively.
  
  
  CONCLUSIONS
  A focally directed treatment strategy using fSRT with or without surgery appears to be an effective initial strategy. Based on the results of this phase II clinical trial, further study is warranted.
authors.affiliation: *Department of Neurological Surgery, Ohio State University Medical Center, Columbus, Ohio; ‡Department of Radiation Oncology, Ohio State University Medical Center, Columbus, Ohio; §Department of Neurological Surgery, Cleveland Clinic, Cleveland, Ohio; ‖Center for Biostatistics, Ohio State University Medical Center, Columbus, Ohio.
authors.forename: Mario
authors.initials: M
authors.lastname: Ammirati
authors.forename: Varun R
authors.initials: VR
authors.lastname: Kshettry
authors.forename: Tariq
authors.initials: T
authors.lastname: Lamki
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: John C
authors.initials: JC
authors.lastname: Grecula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000601:surgery*; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome