title: Neurocognitive outcome in brain metastases patients treated with accelerated-fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from Radiation Therapy Oncology Group Study 91-04.
abstract: OBJECTIVE
  To evaluate neurocognitive outcome as measured by the Mini-Mental Status Examination (MMSE) among patients with unresectable brain metastases randomly assigned to accelerated fractionation (AF) vs. accelerated hyperfractionated (AH) whole-brain radiation therapy (WBRT).
  
  
  METHODS
  The Radiation Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain metastases to a Phase III comparison of AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3 Gy q.d. to 30 Gy). All had a KPS of >or= 70 and a neurologic function status of 0-2. Three hundred fifty-nine patients had MMSEs performed and were eligible for this analysis. Changes in the MMSE were analyzed according to criteria previously defined in the literature.
  
  
  RESULTS
  The median survival was 4.5 months for both arms. The average change in MMSE at 2 and 3 months was a drop of 1.4 and 1.1, respectively, in the AF arm as compared to a drop of 0.7 and 1.3, respectively, in the AH arm (p = NS). Overall, 91 patients at 2 months and 23 patients at 3 months had both follow-up MMSE and computed tomography/magnetic resonance imaging documentation of the status of their brain metastases. When an analysis was performed taking into account control of brain metastases, a significant effect on MMSE was observed with time and associated proportional increase in uncontrolled brain metastases. At 2 months, the average change in MMSE score was a drop of 0.6 for those whose brain metastases were radiologically controlled as compared to a drop of 1.9 for those with uncontrolled brain metastases (p = 0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those whose brain metastases were radiologically controlled as compared to a drop of 6.3 for those with uncontrolled brain metastases (p = 0.02).
  
  
  CONCLUSIONS
  Use of AH as compared to AF-WBRT was not associated with a significant difference in neurocognitive function as measured by MMSE in this patient population with unresectable brain metastases and limited survival. However, control of brain metastases had a significant impact on MMSE.
authors.affiliation: University of Kentucky, Department of Radiation, Lexington, KY, USA. wilregi@pop.uky.edu
authors.forename: W F
authors.initials: WF
authors.lastname: Regine
authors.forename: C
authors.initials: C
authors.lastname: Scott
authors.forename: K
authors.initials: K
authors.lastname: Murray
authors.forename: W
authors.initials: W
authors.lastname: Curran
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000523:psychology / Q000532:radiotherapy* / Q000556:secondary*; D003071:Cognition / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000379:methods; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011795:Surveys and Questionnaires; D016019:Survival Analysis