Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment.

Background: Radiation necrosis is a significant late adverse effect of stereotactic radiotherapy (fSRT) for brain metastases, characterized by inflammatory processes and necrotic degeneration of healthy brain tissue. Objective: To evaluate the relationship between the incidence of radiation necrosis and the distribution of lesions across different brain regions treated with fSRT, with a focus on the potential involvement of stem cell niches. Methods: We conducted a post-hoc analysis of two separate prospective datasets consisting of data from 41 patients previously treated for brain metastases at Campus Bio-Medico University Hospital. Patients underwent fSRT using volumetric-modulated arc radiotherapy (VMAT), with MRI data collected pre- and post-treatment. Lesions were assessed for the presence of radiation necrosis based on radiological and clinical criteria, with a specific focus on their proximity to stem cell niches. A mixed-effects logistic regression model, including age and sex as covariates, was used to identify associations between brain region, stem cell niches, and the likelihood of radiation necrosis. Results: Of 167 lesions observed, 42 (25.1%) were classified as radiation necrosis. The Deep-Periventricular region showed a significantly higher likelihood of radiation necrosis compared to other brain regions (log-OR: 1.25, 95% CI: 0.20–2.30, p = 0.02). Lesions in proximity to stem cell niches were significantly associated with an increased risk of radiation necrosis (log-OR: 1.61, 95% CI: 0.27–2.94, p = 0.018). These findings highlight the differential vulnerability of brain regions and suggest a potential role of stem cell niches in the pathogenesis of radiation necrosis. Conclusion: This study underscores the importance of brain region and stem cell niche involvement in the development of radiation necrosis following stereotactic radiotherapy. These findings might have implications for optimizing radiotherapy planning and developing targeted strategies to mitigate the risk of radiation necrosis. Future research should focus on exploring the molecular mechanisms underlying these associations and evaluating potential neuroprotective interventions.