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


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%.


CONCLUSIONS
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.
Khong
Pek-Lan
PL
Department of Diagnostic Radiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. plkhong@hkucc.hku.hk
Leung
Lucullus H T
LH
Fung
Amy S M
AS
Fong
Daniel Y T
DY
Qiu
Deqiang
D
Kwong
Dora L W
DL
Ooi
Gaik-Cheng
GC
McAlonan
Grainne
G
McAlanon
Grainne
G
Cao
Guang
G
Chan
Godfrey C F
GC
D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000473:pathology / Q000523:psychology*; D002648:Child; D003071:Cognition; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D008527:Medulloblastoma / Q000473:pathology / Q000523:psychology*; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000523:psychology*; D012372:ROC Curve