title: Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial.
abstract: OBJECTIVE
  To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).
  
  
  METHODS
  Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed.
  
  
  RESULTS
  Four hundred one patients were enrolled (251 with non-small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P =.062) and improved neurologic function as assessed by a blinded events review committee (P =.048).
  
  
  CONCLUSIONS
  Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.
authors.affiliation: Department of Neuro-Oncology, Unit 431, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. cameyers@mdanderson.org
authors.forename: Christina A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.forename: Andrea
authors.initials: A
authors.lastname: Bezjak
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: James
authors.initials: J
authors.lastname: Liebmann
authors.forename: Tim
authors.initials: T
authors.lastname: Illidge
authors.forename: Ian
authors.initials: I
authors.lastname: Kunkler
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Caudrelier
authors.forename: Peter D
authors.initials: PD
authors.lastname: Eisenberg
authors.forename: Jacobus
authors.initials: J
authors.lastname: Meerwaldt
authors.forename: Ross
authors.initials: R
authors.lastname: Siemers
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Gaspar
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: See-Chun
authors.initials: SC
authors.lastname: Phan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.forename: Markus F
authors.initials: MF
authors.lastname: Renschler
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology*; D016371:Cranial Irradiation / Q000009:adverse effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D009048:Motor Skills; D011594:Psychometrics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium