ESTRO 2024 - Abstract Book

S134 ESTRO 2024 The mechanisms by which radiation causes cognitive decline is still debated and have been proposed to include microvascular damage, oligodendrocyte decline, loss of white matter integrity, neuroinflammation, metabolic changes, and neuronal dendritic spike damage. Long-term radiation-induced cognitive decline is likely to reflect changes to the white matter, hippocampus and prefrontal cortex, as well as other areas. Several authors have speculated that early dysfunction of surviving neuronal cells alters the signaling microenvironment thus influencing progenitor cell differentiation and cognitive capacity over the long-term. The most studied mechanisms of radiation-induced cognitive impairment include white matter changes and impaired neurogenesis. In the developing brain, neurogenesis occurs in two critical regions: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. From these regions, multipotent neural stem cells are able to differentiate into neurons and glial cells. Reduced neurogenesis after exposure of neural precursors (neural stem cells) to radiation either in single or fractionated doses is one of the main mechanisms thought to be responsible for cognitive deterioration, especially short-term memory impairment. Several strategies to minimize cognitive decline following radiotherapy have been recently proposed. Given the crucial role of hippocampal structures in neurocognitive functions, conformal avoidance of the hippocampal neural stem cell compartment during whole-brain radiotherapy for brain metastases has been reported to preserve neurocognitive functions. Pharmacological interventions and cognitive rehabilitation therapy (CRT) have been the main approaches used to preserve and improve cognitive functioning in these patients. Pharmacological interventions typically include repurposed medications for cognitive functioning in other conditions, such as donepezil, armodafinil, modafinil and methylphenidate. There is limited evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumors who have been treated with cranial irradiation. Invited Speaker Neuro-oncologists focus on radiation induced neurotoxicity, prevention, and treatment strategies, emphasizing the importance of cognitive rehabilitation. Cognitive rehabilitation therapy (CRT) involves neuropsychological interventions that are aimed to improve various domains of cognitive function through the mechanism of neuroplasticity. Radionecrosis (RN) represents the main complication of stereotactic radiotherapy (SRT) for brain metastases. It may be observed in up to 34% of cases (from few months to more than 2 years) after treatment and may be associated with significant morbidity. The pathophysiology of RN is not entirely clear and likely involves vascular changes resulting from endothelial injury within both normal and tumor tissue, mediated by proinflammatory cytokines such as vascular-endothelial growth factor (VEGF), hypoxia-inducible factor, and tumor necrosis factor. The eventual manifestation of RN is secondary to fibrinoid necrosis of small vessels causing ischemia and brain parenchymal necrosis. Treatment of radionecrosis is commonly based on steroids. Recently, the activity of the antivascular endothelial growth factor agent bevacizumab has been reported to improve clinical signs and stabilization/normalization of the vascular permeability in patients unresponsive to steroids. The approved dosing regimen varies from 5mg/kg every 2 weeks to 15mg/kg every 3 weeks. The optimal dosage is still unclear and seems to be lower than that used for antitumor treatment. However, the benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is still unclear.

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