BACKGROUNDThe primary objective of this study was to test the hypothesis that, among survivors of pediatric brain tumors, the association between reduced volumes of normal‐appearing white matter (NAWM) and intellectual/academic achievement deficits can be explained by patient problems with memory and attention.METHODSQuantitative tissue volumes from magnetic resonance imaging scans and neurocognitive assessments were obtained for 40 long‐term survivors of pediatric brain tumors. They were treated with radiotherapy (RT) with or without chemotherapy 2.6–15.3 years earlier (median, 5.7 years) at an age of 1.7–14.8 years (median, 6.5 years). Neurocognitive assessments included standardized tests of intellect (intelligence quotient [IQ]), attention, memory, and academic achievement.RESULTSAnalyses revealed significant impairments in patients' neurocognitive test performance on all measures. After statistically controlling for age at RT and time from RT, significant associations were found between NAWM volumes and both attentional abilities and IQ, and between attentional abilities and IQ. Subsequent analyses supported the hypothesis that attentional abilities, but not memory, could explain a significant amount of the relationship between NAWM and IQ. The final developmental model predicting academic achievement based on NAWM, attentional abilities, and IQ explained approximately 60% of the variance in reading and spelling and almost 80% of the variance in math.CONCLUSIONSThe authors demonstrated that the primary consequence of reduced NAWM among pediatric patients treated for brain tumors was decreased attentional abilities, leading to declining IQ and academic achievement. Cancer 2003;10:2512–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11355

MPH resulted in a statistically significant improvement on measures of attention abilities that cannot be explained by placebo or practice effects.

Children surviving treatment for malignant brain tumors commonly have problems maintaining their premorbid levels of intellectual development and academic achievement. Our group has been especially interested in the effects of treatment on normal appearing white matter (NAWM) on MRI and the influence of NAWM volumes on neurocognitive functioning. The present study assessed NAWM and attentional abilities among 37 long-term survivors of malignant brain tumors, ranging in age from 1.7 to 14.8 (Mdn = 6.5) years at diagnosis, who had been treated with cranial radiation therapy with or without chemotherapy 2.6 to 15.3 (Mdn = 5.7) years earlier. On the Conners' Continuous Performance Test, the Overall Index and 7 of the other 10 indices were significantly deficient compared to age- and gender-corrected normative values. After statistically controlling for the effects of age at diagnosis and time elapsed from treatment, 5 of the 8 indices were significantly associated with cerebral white matter volumes and/or specific regional white matter volumes of the prefrontal/frontal lobe and cingulate gyrus. No gender effects were observed. The results of the present study further support the contention that NAWM is an important substrate for treatment-induced neurocognitive problems among survivors of malignant brain tumors of childhood.