title: Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.
abstract: BACKGROUND
  In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.
  
  
  OBJECTIVE
  To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.
  
  
  METHODS
  Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.
  
  
  METHODS
  Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).
  
  
  METHODS
  The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.
  
  
  RESULTS
  The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.
  
  
  CONCLUSIONS
  Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.
  
  
  BACKGROUND
  umin.ac.jp/ctr Identifier: C000000412.
authors.affiliation: Departments of Radiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. h-aoyama@umin.ac.jp
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shirato
authors.forename: Masao
authors.initials: M
authors.lastname: Tago
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Toyoda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kenjyo
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oya
authors.forename: Saeko
authors.initials: S
authors.lastname: Hirota
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shioura
authors.forename: Etsuo
authors.initials: E
authors.lastname: Kunieda
authors.forename: Taisuke
authors.initials: T
authors.lastname: Inomata
authors.forename: Kazushige
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Norio
authors.initials: N
authors.lastname: Katoh
authors.forename: Gen
authors.initials: G
authors.lastname: Kobashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary* / Q000601:surgery; D002423:Cause of Death; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D011832:Radiation Injuries; D016634:Radiosurgery; D016879:Salvage Therapy; D016019:Survival Analysis