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Project

The impact of radiotherapy on the human connectome and neurocognitive outcome in pediatric brain tumor patients: towards neuroimaging-guided treatment optimization

For pediatric brain tumor patients, cranial irradiation is known to result in long-term neurocognitive decline. Although radiation-induced neurotoxic mechanisms are hypothesized, the pathophysiology and the extent of neurological damage remains poorly understood. Given the rapidly evolving innovative treatments, optimization of brain tumor treatment requires a good estimation of the extent and dose-dependency of neural damage due to cranial radiotherapy. As from 2020 onwards proton beam therapy (PBT) will be available in Belgium for pediatric brain tumor patients, early detection of neurodevelopmental delay will be critical in order to closely follow-up and optimize the impact of this technology. In this respect, advanced neuroimaging methods are useful to quantify neuroanatomical changes as well as functional outcomes. Multi-modal MRI neuroimaging studies reported anatomical as well as functional brain alterations after photon (X-ray) beam radiotherapy (XRT). Currently, such possible side effects of PBT are insufficiently studied. PBT exploits the physical properties of protons to target the tumor more precisely and result in decreased secondary (scatter) radiation, and thus decreased normal tissue damage. Hence, PBT holds promise to improve treatment while reducing impact on neurocognitive functioning. Still, given that PBT is a relatively new treatment modality, studies assessing the extent of induced neural changes and cognitive decline are currently lacking. Furthermore, the functional importance of specific brain areas to spare from radiation needs attention in order to optimize PBT planning. We aim to detect neuropathological mechanisms and vulnerable brain regions, by implementing a state-of-the art multimodal neuroimaging protocol in one cross-sectional survivor study as well as in one longitudinal follow-up study of pediatric brain tumor patients (T1-weighted MRI, multishell diffusion MRI, resting state fMRI, FLAIR and SWI) combined with neurocognitive assessments. Neuroimaging biomarkers are derived from the MRI scans and dose-response functions for these biomarkers are investigated. The main objective of this monocentric study is to limit neurotoxicity of PBT and work towards optimization of the treatment in pediatric brain tumor patients.

Date:1 Oct 2020 →  30 Sep 2021
Keywords:pediatric brain tumor, proton beam therapy, Multi-modal MRI neuroimaging
Disciplines:Paediatrics
Project type:PhD project