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

BackgroundRadiation 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.ObjectiveTo evaluate the relationship between the incidence of radiation necrosis and...

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Main Authors: Carlo A. Mallio, Ugo Ferrari, Gianfranco Di Gennaro, Matteo Pileri, Caterina Bernetti, Enrica Polo, Emma Gangemi, Francesca Giannetti, Paolo Matteucci, Bruno Beomonte Zobel, Edy Ippolito, Sara Ramella
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Radiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fradi.2025.1554017/full
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author Carlo A. Mallio
Carlo A. Mallio
Ugo Ferrari
Ugo Ferrari
Gianfranco Di Gennaro
Matteo Pileri
Matteo Pileri
Caterina Bernetti
Caterina Bernetti
Enrica Polo
Enrica Polo
Emma Gangemi
Francesca Giannetti
Francesca Giannetti
Paolo Matteucci
Paolo Matteucci
Bruno Beomonte Zobel
Bruno Beomonte Zobel
Edy Ippolito
Edy Ippolito
Sara Ramella
Sara Ramella
author_facet Carlo A. Mallio
Carlo A. Mallio
Ugo Ferrari
Ugo Ferrari
Gianfranco Di Gennaro
Matteo Pileri
Matteo Pileri
Caterina Bernetti
Caterina Bernetti
Enrica Polo
Enrica Polo
Emma Gangemi
Francesca Giannetti
Francesca Giannetti
Paolo Matteucci
Paolo Matteucci
Bruno Beomonte Zobel
Bruno Beomonte Zobel
Edy Ippolito
Edy Ippolito
Sara Ramella
Sara Ramella
author_sort Carlo A. Mallio
collection DOAJ
description BackgroundRadiation 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.ObjectiveTo 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.MethodsWe 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.ResultsOf 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.ConclusionThis 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.
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spelling doaj-art-4b6035bd7aa84e8fa7ad818571ae02202025-08-20T03:06:13ZengFrontiers Media S.A.Frontiers in Radiology2673-87402025-04-01510.3389/fradi.2025.15540171554017Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatmentCarlo A. Mallio0Carlo A. Mallio1Ugo Ferrari2Ugo Ferrari3Gianfranco Di Gennaro4Matteo Pileri5Matteo Pileri6Caterina Bernetti7Caterina Bernetti8Enrica Polo9Enrica Polo10Emma Gangemi11Francesca Giannetti12Francesca Giannetti13Paolo Matteucci14Paolo Matteucci15Bruno Beomonte Zobel16Bruno Beomonte Zobel17Edy Ippolito18Edy Ippolito19Sara Ramella20Sara Ramella21Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyDepartment of Health Sciences, Chair of Medical Statistics, University of Catanzaro “Magna Græcia”, Catanzaro, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyDepartment of Human Neurosciences, Sapienza University of Rome, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyFondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyResearch Unit of Radiation Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, ItalyBackgroundRadiation 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.ObjectiveTo 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.MethodsWe 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.ResultsOf 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.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fradi.2025.1554017/fullbrain MRIradiation necrosisstem cell nichesstereotactic radiotherapybrain metastases
spellingShingle Carlo A. Mallio
Carlo A. Mallio
Ugo Ferrari
Ugo Ferrari
Gianfranco Di Gennaro
Matteo Pileri
Matteo Pileri
Caterina Bernetti
Caterina Bernetti
Enrica Polo
Enrica Polo
Emma Gangemi
Francesca Giannetti
Francesca Giannetti
Paolo Matteucci
Paolo Matteucci
Bruno Beomonte Zobel
Bruno Beomonte Zobel
Edy Ippolito
Edy Ippolito
Sara Ramella
Sara Ramella
Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
Frontiers in Radiology
brain MRI
radiation necrosis
stem cell niches
stereotactic radiotherapy
brain metastases
title Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
title_full Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
title_fullStr Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
title_full_unstemmed Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
title_short Brain MRI and regional vulnerabilities to radiation necrosis: investigating the impact of stereotactic radiotherapy in brain metastases treatment
title_sort brain mri and regional vulnerabilities to radiation necrosis investigating the impact of stereotactic radiotherapy in brain metastases treatment
topic brain MRI
radiation necrosis
stem cell niches
stereotactic radiotherapy
brain metastases
url https://www.frontiersin.org/articles/10.3389/fradi.2025.1554017/full
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