title: Radiotherapeutic management of brain metastases: a systematic review and meta-analysis.
abstract: BACKGROUND
  The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness.
  
  
  METHODS
  A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity.
  
  
  RESULTS
  Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive.
  
  
  CONCLUSIONS
  For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.
authors.affiliation: Department of Radiation Oncology, Toronto-Sunnybrook Regional Cancer Centre, 2075 Bayview Avenue, Toronto, Ont., Canada M4N 3M5. may.tsao@sw.ca
authors.forename: May N
authors.initials: MN
authors.lastname: Tsao
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Lloyd
authors.forename: Rebecca K S
authors.initials: RK
authors.lastname: Wong
authors.forename: Eileen
authors.initials: E
authors.lastname: Rakovitch
authors.forename: Edward
authors.initials: E
authors.lastname: Chow
authors.forename: Normand
authors.initials: N
authors.lastname: Laperriere
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D016371:Cranial Irradiation; D019583:Dose Fractionation, Radiation; D006801:Humans; D018579:Patient Selection; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome