title: Neuropsychological functioning of children treated for acute lymphoblastic leukemia: impact of whole brain radiation therapy.
abstract: OBJECTIVE
  To provide one of the first prospective reports examining neuropsychological outcomes for children treated with 1800 cGy whole brain radiotherapy (WBRT) and prophylactic chemotherapy versus prophylactic chemotherapy alone for acute lymphoblastic leukemia (ALL). Acute and long-term neuropsychological toxicities associated with WBRT are compared.
  
  
  METHODS
  This multisite study included 188 children, ages 4-21 years at enrollment, who were assessed with standardized neuropsychological tests at 9, 21, and 48 months after diagnosis with intermediate risk ALL. All participating children were receiving treatment on a parent study CCG105.
  
  
  RESULTS
  Verbal intelligence (VIQ) scores for children receiving WBRT was significantly lower than VIQ for prophylactic chemotherapy at the 48-month time point (p < 0.05). A significant cross-level interaction between time since diagnosis and treatment condition was observed (p < 0.05). WBRT did not result in differences in PIQ; both groups of children demonstrated comparable increases in PIQ. Neuropsychological findings at 48 months after diagnosis indicated diminished performance in neuromotor, visual-motor coordination, and executive functioning for children receiving WBRT. Academic achievement was unaffected by WBRT at 4 years after diagnosis.
  
  
  CONCLUSIONS
  The measurement of verbal and performance IQ as a primary endpoint in ALL clinical trials is critical to characterizing neuropsychological late effects. A trajectory of decline in neuropsychological functioning, specifically verbal IQ, was observed. Missing data within the trial occurred at random and did not impact results observed. The impact of WBRT becomes evident at 48 months after diagnosis, suggesting the need for long-term follow-up beyond the time frame typically used in Phase III trials.
authors.affiliation: University of New Mexico Health Sciences Center, MSC10-5590, 1 University of New Mexico, Albuquerque, NM, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Annett
authors.forename: Sarah
authors.initials: S
authors.lastname: Hile
authors.forename: Edward
authors.initials: E
authors.lastname: Bedrick
authors.forename: Alicia S
authors.initials: AS
authors.lastname: Kunin-Batson
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
authors.forename: Leanne
authors.initials: L
authors.lastname: Embry
authors.forename: Willliam E
authors.initials: WE
authors.lastname: MacLean
authors.forename: Robert B
authors.initials: RB
authors.lastname: Noll
mesh_terms: D000124:Achievement; D000293:Adolescent; D001288:Attention / Q000528:radiation effects*; D001921:Brain; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000528:radiation effects; D056344:Executive Function / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008568:Memory / Q000528:radiation effects*; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000523:psychology / Q000532:radiotherapy*; D011446:Prospective Studies; D011597:Psychomotor Performance / Q000528:radiation effects*; D055815:Young Adult
keywords: Leukemia; children; late effects; neuropsychological outcomes; whole brain radiotherapy