Central Nervous System Injury, Neurocognitive and Quality of Life Outcomes in Children with Brain Tumors Treated with Chemotherapy

Two-thirds of children diagnosed with brain tumors achieve long-term survival, and increasingly, children younger than 5-6 years at diagnosis are treated with high-dose chemotherapy protocols, delaying or foregoing cranial radiation. Intrathecal chemotherapy is associated with white matter loss, with systemic administration of certain agents also damaging healthy brain tissue. However, effects of systemic chemotherapy on the brain in children with tumors are unclear. Our first objective was to compare structural neural integrity with magnetic resonance imaging procedures in children with brain tumors (n = 7, mean age 8.3 years), treated with chemotherapy a mean of 5.4 years earlier, to age- and gender-matched healthy controls (n = 9, mean age 9.3 years). We also sought to explore the relationship between tissue loss, memory and executive functioning and quality of life (QOL) effects. Magnetic resonance imaging data were collected using a diffusion tensor imaging protocol to evaluate tissue integrity throughout the brain, and in specific regions of interest. Voxel-based morphometry was used to determine differences between groups. In addition, we used neurocognitive, behavioral and QOL assessments. Mean diffusivity and fractional anisotropy maps were obtained from normalized, smoothed images, and the two groups were compared using analysis of covariance, with age and gender as covariates. Higher mean diffusivity values emerged in patients over controls (p < 0.05, corrected for multiple comparisons), and were especially apparent in the central thalamus, internal and external capsules, putamen, globus pallidus and pons. No significant differences emerged in fractional anisotropy values between groups. The patient group had lower brain-to-CSF ratio (p = .03), assessed with volumetric analyses. Overall QOL, school functioning, and psychosocial functioning were significantly lower in patients. The majority of patients scored within the average range on memory and executive functioning tests, and behavior assessment did not differ from controls. Significantly higher mean diffusivity, indicating long-term damage, appeared in multiple areas in patients 5 years after treatment with chemotherapy. Early intervention may provide neuroprotection or repair to alleviate the long-term consequences of the original trauma and chemotherapy-related damage