White Matter Anisotropy in Post-Treatment Childhood Cancer Survivors: Preliminary Evidence of Association With Neurocognitive Function

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 (ΔFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between ΔFA%, 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 ΔFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85. Results ΔFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r2 = 0.237; P = .028), and PIQ (adjusted r2 = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best ΔFA% 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.