Neurocognition and mean radiotherapy dose to vulnerable brain structures: new organs at risk?

BACKGROUND: Children with brain tumors are at high risk of neurocognitive decline after radiotherapy (RT). However, there is a lack of studies on how RT doses to organs at risk (OARs) impacts neurocognition. The aim of this study was to examine dose-risk relationships for mean RT dose to different brain structures important for neurocognitive networks. We explored previously established OARs and potentially new OARs. METHODS: A sample of 44 pediatric brain tumor survivors who had received proton and/or photon RT were included. Correlations between mean RT doses to OARs and IQ were analyzed. Previously established OARs were cochleae, optic chiasm, optic nerve, pituitary gland, hypothalamus, hippocampus and pons. Potential new OARs for RT-induced neurocognitive decline were cerebellum, vermis and thalamus. RESULTS: Mean RT dose to different OARs correlated with several IQ subtests. Higher mean RT dose to cochleae, optic nerve, cerebellum, vermis and pons was correlated with lower performance on particularly full-scale IQ (FIQ), Perceptual Reasoning (PRI), Working Memory (WMI) and Processing Speed Index (PSI). Higher mean RT dose to hippocampus correlated with lower performance on processing speed and working memory. For those receiving whole brain RT (WBRT), higher mean RT dose to the pituitary gland correlated with lower performance on working memory. CONCLUSION: A high dose-risk correlation was found between IQ subtests and mean RT dose in established and potential new OARs. Thus, in the lack of validated dose constraints for vulnerable brain structures, a parsimonious approach in RT planning should be considered to preserve neurocognitive networks.

Neurocognitive Functions Before and After Radiotherapy in Pediatric Brain Tumor Survivors.

BACKGROUND: The numbers of pediatric brain tumor survivors are increasing due to improved treatment protocols and multimodal treatments. Many survivors have neurocognitive sequelae, especially after radiotherapy. Neuropsychologic assessment is therefore essential to interpret clinical outcome, evaluate treatments protocol, and implement rehabilitation interventions. The overall aim of this study was to describe neurocognitive functions before and after radiotherapy. We also aimed to explore potential confounding risk factors that could affect the interpretation of radiotherapy-induced neurocognitive decline. METHODS: Fifty pediatric brain tumor survivors who had received radiotherapy (five years or more ago) were included. Clinical characteristics, potential confounding risk factors, radiotherapy plans, and neurocognitive functions on intelligence quotient (IQ) and neuropsychologic measurements were analyzed before and after radiotherapy. RESULTS: Neurocognitive functions were affected before radiotherapy and were progressively aggravated thereafter. The last neuropsychologic assessment after radiotherapy varied between two and 139 months. Nineteen patients were tested five years after radiotherapy, and 90% of them performed ≥1 S.D. below the normative mean on IQ measurements. Several potential confounding risk factors including those induced by radiotherapy were associated with lower performance on perceptual function, working memory, and processing speed. Longer time after radiotherapy was particularly associated with lower performance on working memory and processing speed. Importantly, the neuropsychologic assessments revealed more comprehensive problems than could be inferred from IQ measurements alone. CONCLUSIONS: Our study underpins the importance of systematic and structured neuropsychologic assessment before and after radiotherapy. The timing of the assessment is important, and potential confounding risk factors need to be identified to better evaluate radiotherapy-induced neurocognitive decline.