Abstract
PurposeTo study a robust and reproducible procedure to investigate a relation between focal brain radiotherapy (RT) low doses, neurocognitive impairment and late White Matter and Gray Matter alterations, as shown by Diffusion Tensor Imaging (DTI), in children.Methods and materialsForty-five patients (23 males and 22 females, median age at RT 6.2 years, median age at evaluations 11.1 years) who had received focal RT for brain tumors were recruited for DTI exams and neurocognitive tests. Patients’ brains were parceled in 116 regions of interest (ROIs) using an available segmented atlas. After the development of an ad hoc, home-made, multimodal and highly deformable registration framework, we collected mean RT doses and DTI metrics values for each ROI. The pattern of association between cognitive scores or domains and dose or DTI values was assessed in each ROI through both considering and excluding ROIs with mean doses higher than 75% of the prescription. Subsequently, a preliminary threshold value of dose discriminating patients with and without neurocognitive impairment was selected for the most relevant associations.ResultsThe workflow allowed us to identify 10 ROIs where RT dose and DTI metrics were significantly associated with cognitive tests results (p<0.05). In 5/10 ROIs, RT dose and cognitive tests were associated with p<0.01 and preliminary RT threshold dose values, implying a possible cognitive or neuropsychological damage, were calculated. The analysis of domains showed that the most involved one was the “school-related activities”.ConclusionThis analysis, despite being conducted on a retrospective cohort of children, shows that the identification of critical brain structures and respective radiation dose thresholds is achievable by combining, with appropriate methodological tools, the large amount of data arising from different sources. This supported the design of a prospective study to gain stronger evidence.
Highlights
Late neurocognitive sequelae in childhood brain tumor survivors have been extensively documented [1,2,3,4] and are known to correlate to several risk factors, such as radiotherapy (RT) doses, fraction size, target volume and young patient age [2, 5,6,7]
The workflow allowed us to identify 10 regions of interest (ROIs) where RT dose and Diffusion Tensor Imaging (DTI) metrics were significantly associated with cognitive tests results (p
The analysis of domains showed that the most involved one was the “school-related activities”. This analysis, despite being conducted on a retrospective cohort of children, shows that the identification of critical brain structures and respective radiation dose thresholds is achievable by combining, with appropriate methodological tools, the large amount of data arising from different sources
Summary
Late neurocognitive sequelae in childhood brain tumor survivors have been extensively documented [1,2,3,4] and are known to correlate to several risk factors, such as radiotherapy (RT) doses, fraction size, target volume and young patient age [2, 5,6,7]. RT brain damage usually involves white matter injuries and demyelination (or structural degradation) of axon fibers, causing the disruption of trans-synaptic communications [11]. These tissue alterations cannot be effectively assessed with morphological Magnetic Resonance Imaging (MRI). Finding any correlation between RT dose, neurocognitive measurements and GM-WM indicators of “integrity” (like DTI-derived variables) may help to expand our knowledge about the local, long-term cerebral structural and cognitive effects of low radiation doses and may be used to optimize treatment planning procedures with dose constraints for each eloquent brain functional area. Robust experimental dose-effect curves for specific pediatric brain areas have not been defined yet
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