title: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial.
abstract: BACKGROUND
  Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).
  
  
  METHODS
  Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.
  
  
  RESULTS
  From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institutions--167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6.5 vs 4.9 months, p=0.0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0.03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0.0001) or a favourable histological status (p=0.0121).
  
  
  CONCLUSIONS
  WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.
authors.affiliation: Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA. david.andrews@jefferson.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.forename: Charles B
authors.initials: CB
authors.lastname: Scott
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sperduto
authors.forename: Adam E
authors.initials: AE
authors.lastname: Flanders
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.forename: Michael C
authors.initials: MC
authors.lastname: Schell
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: William
authors.initials: W
authors.lastname: Demas
authors.forename: Janice
authors.initials: J
authors.lastname: Ryu
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011832:Radiation Injuries; D016634:Radiosurgery / Q000009:adverse effects; D011879:Radiotherapy Dosage; D015996:Survival Rate