Chemoradiation impairs normal developmental cortical thinning in medulloblastoma

Abstract

Medulloblastoma patients are treated with surgery, radiation and chemotherapy. Radiation dose to the temporal lobe may be associated with neurocognitive sequelae. Longitudinal changes of temporal lobe cortical thickness may result from neurodevelopmental processes such as synaptic pruning. This study applies longitudinal image analysis to compare developmental change in cortical thickness in medulloblastoma (MB) patients who were treated by combined modality therapy to that of cerebellar juvenile pilocytic astrocytoma (JPA) patients who were treated by surgery alone. We hypothesized that the rates of developmental change in cortical thickness would differ between these two groups. This retrospective cohort study assessed changes in cortical thickness over time between MB and JPA patients. High-resolution magnetic resonance (MR) images of 14 MB and 7 JPA subjects were processed to measure cortical thickness of bilateral temporal lobe substructures. A linear mixed effects model was used to identify differences in substructure longitudinal changes in cortical thickness. The left temporal lobe exhibited overall increased cortical thickness in MB patients relative to JPA patients who showed overall cortical thinning (mean annual cortical thickness change: MB 0.14 mm/year versus JPA −0.018 mm/year across all substructures), particularly in the inferior temporal lobe substructures (p < 0.0001). The cortical thickness change of the right temporal lobe substructures exhibited similar, though attenuated trends (p = 0.002). MB patients exhibit overall increased cortical thickness rather than cortical thinning as seen in JPA patients and as expected in normal cortical development. These observations are possibly due to chemoradiation induced-disruption of normal neuronal mechanisms. Longitudinal image analysis may identify early biomarkers for neurocognitive function with routine imaging.

Neurocognitive Dysfunction After Treatment for Pediatric Brain Tumors: Subtype-Specific Findings and Proposal for Brain Network-Informed Evaluations

“…In comparison to PiA, MB patients show decreased cerebral blood flow [18], more evident leukoencephalopathy [30], and less cortical thinning throughout development [41].…”

Precision based approach to tailoring radiotherapy in the multidisciplinary management of pediatric central nervous system tumors

“… 111 , 112 Cortical thinning may be dose dependent and different parts of the cortex may be more susceptible. 114 , 115 In addition, cerebral microbleeds was found to be more frequent in children treated with cranial radiotherapy and could be a contributing factor to worse neurocognitive function. 116 , 117 In the Rad-Art study, cerebral microbleeds was found to occur in almost half of children treated with cranial radiotherapy 5 years post treatment and was associated with worse executive function and performed worse in delayed recall, verbal learning, attention, and working memory.…”