Sahaja Acharya1,2, Yian Guo3, Tushar Patni3, Yimei Li3, Chuang Wang1, Melissa Gargone1, Jason M Ashford4, Lydia Wilson1, Austin Faught1, Wilburn E Reddick5, Zoltan Patay5, Amar Gajjar6, Heather M Conklin4, Thomas E Merchant1. 1. Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN. 2. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine, Baltimore, MD. 3. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN. 4. Department of Psychology, St Jude Children's Research Hospital, Memphis, TN. 5. Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN. 6. Division of Neuro-Oncology, St Jude Children's Research Hospital, Memphis, TN.
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.
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.
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