Association Between Brain Substructure Dose and Cognitive Outcomes in Children With Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning

Abstract

PURPOSE To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03. PATIENTS AND METHODS Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline. RESULTS One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose–volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively. CONCLUSION Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure–informed RT planning may mitigate neurocognitive impairment.

Optimization of hippocampus sparing during whole brain radiation therapy with simultaneous integrated boost—tutorial and efficacy of complete directional hippocampal blocking

“…Furthermore, although the hippocampus is crucial for memory consolidation, it is not the only structure of interest. Other brain substructures, including the corpus callosum and frontal white matter, play a key role in specific neurocognitive functions, such as attention and processing speed [ 36 , 37 ]. Even though hippocampal blocking did not significantly affect whole brain dose homogeneity and conformity, future research is warranted to evaluate possible dose variations in these particular structures and their clinical implications.…”

Prediction Models for Radiation-Induced Neurocognitive Decline in Adult Patients With Primary or Secondary Brain Tumors: A Systematic Review

“…Recent studies have documented deleterious associations between radiation dose to brain substructures and neurocognitive score in both pediatric and adult patients ( Toussaint et al, 2019 ; Haldbo-Classen et al, 2020 ; Acharya et al, 2021 ; Eekers et al, 2021 ; Rodríguez de Dios et al, 2021 ). This is in line with the significant predictive power of radiation dose to the hippocampus, subventricular zone, and cerebellum in the available prediction models.…”

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review

“…The severity of acute and late chronic effects of RT are partially related to the dose received by critical structures [ 54 , 55 ]. In particular, the dose received by brain substructures is correlated with critical neurocognitive outcomes [ 56 ], which may impact HRQoL. However, no studies meeting the inclusion criteria describe the association between irradiation of a specific organ or region and the associated HRQoL outcomes.…”