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

From the Departments of Diagnostic Radiology, Clinical Oncology, Clinical Psychology, Nursing Studies, Psychiatry, Paediatric and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong; GE Medical Systems Asia, Hong Kong, China

Address reprint requests to Pek-Lan Khong, Department of Diagnostic Radiology, Blk K, Rm 406, Queen Mary Hospital, The University of Hong Kong, 102 Pokfulam Rd, Hong Kong; e-mail: plkhong{at}hkucc.hku.hk

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 (FA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between FA%, 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 FA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85.

RESULTS: FA% 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 FA% 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.

Supported by Hong Kong RGC CERG Grant Ref: HKU 7416/03M.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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