Long term survival in children with brain and CNS tumours has reached an all-time high of nearly 80%. Although radiotherapy remains a mainstay in the treatment of these tumours, it is associated with cognitive and endocrinal side effects, which are generally irreversible. ‘Cognitive side effects include loss of memory and attention, decreased processing speed, and a decline in IQ points, which impair the quality of life of the survivors’, explains Barazzuol. ‘Endocrine side effects include reduced production of several hormones, like the growth hormone’.
For this international project, led by Martin McCabe from the University of Manchester, researchers aim to elucidate the response of different brain regions to radiation and how endocrine dysfunction may affect cognitive outcome. ‘The reduced production of growth hormone, for example, is caused by radiation damage in the hypothalamus and pituitary gland’, explains Barazzuol. The activity at the UMCG will hence encompass pre-clinical studies elucidating the role of the hypothalamic-pituitary-adrenal (HPA) axis. Barazzuol: ‘Patients who received growth hormone replacement earlier after irradiation showed a better cognitive outcome than patients who received this treatment much later. This suggests that there is an interaction between the hypothalamus and parts of the brain that have more cognitive functions.’
During the project, Dr. Barazzuol aims to clarify the neuroimmune response of the developing brain after irradiation. On top of that, she aims to develop possible interventions that could modulate the neuroimmune response. ‘We plan to use some drugs that can deplete or repopulate the immune cells of the brain’, says Barazzuol. ‘Besides, once the role of the hypothalamus is clear, we want to find out whether we can spare this brain region during irradiation and hence improve the cognitive outcome.’ Barazzuol expects that we can improve the later quality of life of the surviving patients by focusing on improving their cognitive outcomes as early as possible.
The project also aims at mapping radiation-induced cognitive deficits to specific brain regions. ‘In Manchester, they use an image-based data mining and machine learning approach based on MRI or CT scans and cognitive outcome to study the effect of radiation on different brain regions’, says Barazzuol. ‘These models are usually developed on a single data set. Because of this, they might not work on other sets of data. Together with the Princess Máxima Centre in Utrecht, we aim to validate the model using a set of clinical data from the UMCG Proton Therapy Centre’. The clinical work at the UMCG is led by Dr. John Maduro (radiation oncologist) and will be a collaboration between the UMCG, the Princess Máxima Centre, St. Jude Children’s Research Hospital in Memphis and the Christie Hospital in Manchester.
