White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function

J Clin Oncol. 2006 Feb 20;24(6):884-90. doi: 10.1200/JCO.2005.02.4505.

Abstract

Purpose: We aim to determine if the loss of white matter fractional anisotropy (FA), measured by diffusion tensor magnetic resonance imaging (DTI), in post-treatment childhood medulloblastoma (MED) and acute lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient (IQ) scores.

Materials and methods: MED and ALL survivors (n = 30; 20 male, 10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited for DTI and IQ tests. In this cross-sectional study, age-matched normal control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1 years) DTI was obtained to compute percentage difference in white matter FA (DeltaFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between DeltaFA%, age at treatment, irradiation dose, time interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). Receiver operating characteristics curves were used to determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85.

Results: DeltaFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ (adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was -3.3% with specificities of 100% and sensitivities ranging from 77.8% to 87.5%.

Conclusion: Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anisotropy
  • Brain / drug effects
  • Brain / pathology*
  • Brain / radiation effects
  • Case-Control Studies
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / psychology*
  • Child
  • Cognition*
  • Cross-Sectional Studies
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Humans
  • Intelligence Tests
  • Intelligence*
  • Male
  • Medulloblastoma / pathology
  • Medulloblastoma / psychology*
  • Multivariate Analysis
  • Neuropsychological Tests
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / psychology*
  • ROC Curve