title: Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score.
abstract: OBJECTIVE
  Decline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline.
  
  
  METHODS
  A total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brain irradiation.
  
  
  RESULTS
  Using a multiple linear regression model to correct for initial IQ and age at treatment, patients who received a dose of 36 Gy to the whole brain were estimated to score 8.2 points less on IQ testing than those with 24 Gy (95% confidence interval [CI], 1.8 to 14.6) and 12.3 points less than those who received 18 Gy (95% CI, 2.7 to 21.7). Older age at the time of irradiation resulted in less decline in subsequent IQ score. The predicted IQ decline is 11.9 points less in a 10-year-old patient than in a 3-year-old patient (95% CI, 4.2 to 19.6) for equivalent doses of irradiation. The model to predict IQ accounts for half the total variation in IQ score. There was no significant difference between the coefficients that reflected IQ decrease from radiation dose between subgroups who had ALL versus those with PNET.
  
  
  CONCLUSIONS
  One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiation. Our findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.
authors.affiliation: Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: J H
authors.initials: JH
authors.lastname: Silber
authors.forename: J
authors.initials: J
authors.lastname: Radcliffe
authors.forename: V
authors.initials: V
authors.lastname: Peckham
authors.forename: G
authors.initials: G
authors.lastname: Perilongo
authors.forename: P
authors.initials: P
authors.lastname: Kishnani
authors.forename: M
authors.initials: M
authors.lastname: Fridman
authors.forename: J W
authors.initials: JW
authors.lastname: Goldwein
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001921:Brain / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000528:radiation effects*; D007361:Intelligence Tests; D016014:Linear Models; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000532:radiotherapy*; D011878:Radiotherapy / Q000379:methods