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A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease
BACKGROUND: Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospin...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132465/ https://www.ncbi.nlm.nih.gov/pubmed/37124531 http://dx.doi.org/10.3389/fonc.2023.1105395 |
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author | Knox, Aaron J. Van Court, Benjamin Oweida, Ayman Barsh, Elinor DeSisto, John Flannery, Patrick Lemma, Rakeb Chatwin, Hannah Vibhakar, Rajeev Dorris, Kathleen Serkova, Natalie J. Karam, Sana D. Gilani, Ahmed Green, Adam L. |
author_facet | Knox, Aaron J. Van Court, Benjamin Oweida, Ayman Barsh, Elinor DeSisto, John Flannery, Patrick Lemma, Rakeb Chatwin, Hannah Vibhakar, Rajeev Dorris, Kathleen Serkova, Natalie J. Karam, Sana D. Gilani, Ahmed Green, Adam L. |
author_sort | Knox, Aaron J. |
collection | PubMed |
description | BACKGROUND: Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor. METHODS: We used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation. RESULTS: Mice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation. CONCLUSION: In a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control. |
format | Online Article Text |
id | pubmed-10132465 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101324652023-04-27 A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease Knox, Aaron J. Van Court, Benjamin Oweida, Ayman Barsh, Elinor DeSisto, John Flannery, Patrick Lemma, Rakeb Chatwin, Hannah Vibhakar, Rajeev Dorris, Kathleen Serkova, Natalie J. Karam, Sana D. Gilani, Ahmed Green, Adam L. Front Oncol Oncology BACKGROUND: Diffuse midline glioma (DMG) is an aggressive pediatric central nervous system tumor with strong metastatic potential. As localized treatment of the primary tumor improves, metastatic disease is becoming a more important factor in treatment. We hypothesized that we could model craniospinal irradiation (CSI) through a DMG patient-derived xenograft (PDX) model and that CSI would limit metastatic tumor. METHODS: We used a BT245 murine orthotopic DMG PDX model for this work. We developed a protocol and specialized platform to deliver craniospinal irradiation (CSI) (4 Gy x2 days) with a pontine boost (4 Gy x2 days) and compared metastatic disease by pathology, bioluminescence, and MRI to mice treated with focal radiation only (4 Gy x4 days) or no radiation. RESULTS: Mice receiving CSI plus boost showed minimal spinal and brain leptomeningeal metastatic disease by bioluminescence, MRI, and pathology compared to mice receiving radiation to the pons only or no radiation. CONCLUSION: In a DMG PDX model, CSI+boost minimizes tumor dissemination compared to focal radiation. By expanding effective DMG treatment to the entire neuraxis, CSI has potential as a key component to combination, multimodality treatment for DMG designed to achieve long-term survival once novel therapies definitively demonstrate improved local control. Frontiers Media S.A. 2023-04-12 /pmc/articles/PMC10132465/ /pubmed/37124531 http://dx.doi.org/10.3389/fonc.2023.1105395 Text en Copyright © 2023 Knox, Van Court, Oweida, Barsh, DeSisto, Flannery, Lemma, Chatwin, Vibhakar, Dorris, Serkova, Karam, Gilani and Green https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Knox, Aaron J. Van Court, Benjamin Oweida, Ayman Barsh, Elinor DeSisto, John Flannery, Patrick Lemma, Rakeb Chatwin, Hannah Vibhakar, Rajeev Dorris, Kathleen Serkova, Natalie J. Karam, Sana D. Gilani, Ahmed Green, Adam L. A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title | A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title_full | A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title_fullStr | A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title_full_unstemmed | A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title_short | A novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
title_sort | novel preclinical model of craniospinal irradiation in pediatric diffuse midline glioma demonstrates decreased metastatic disease |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132465/ https://www.ncbi.nlm.nih.gov/pubmed/37124531 http://dx.doi.org/10.3389/fonc.2023.1105395 |
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