Abstract

BACKGROUND: Pediatric brain tumor survivors may develop neuropsychological impairments after treatment. The first months after treatment could be a crucial time-window where the development of the brain may be affected by different types of treatments. For example, deficits in memory and learning related to hippocampal damage have resulted in radiotherapy dose constraints to the hippocampus. However, other limbic system substructures, important for cognition or behavior, may suffer from collateral doses. Therefore, we investigated the early effect of treatment on limbic structure volume. We hypothesized that radiotherapy (vs. no radiotherapy) would contribute to a decrease in volume of the limbic structures. METHODS AND MATERIALS: Thirty-eight patients with a tumor in the posterior fossa region (medulloblastoma n=12; pilocytic astrocytoma n=24; other=2) who were diagnosed between June 2018 and September 2020 and were alive ≥1 year diagnosis were included. Patients receiving neurosurgery only (n=26) were compared to patients treated with neurosurgery, proton therapy and chemotherapy (n=12). Limbic structures were automatically segmented in 111 MRI scans. These structures were amygdala, hippocampus (CA1+CA2/3), subiculum, dentate gyrus, parahippocampal gyrus, fornix, mammillary bodies, nucleus accumbens and thalamo-anteroventral nucleus of thalamus. RESULTS: Analyses revealed a significant negative effect of time on the amygdala (p<0.01), hippocampus (CA1) (p<0.001), and dentate gyrus (p<0.01). This indicates that these structures decreased in volume within the first year after diagnosis, independent of radiation treatment. Furthermore, an interaction effect was found between time and radiation in the subiculum (p=0.02) and fornix (p=0.052). CONCLUSION: These results indicate that the volumetric decline were stronger for the patients that received proton radiation. Future comparisons will test how results relate to the volumes in healthy children of the same age. Also, we will investigate whether this abnormal development is associated to the radiation dose and how it relates to the neuropsychological outcomes of the child over time.

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