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Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice

Patients with recurrent malignant glioma treated with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), alone or in combination with irinotecan have had impressive reductions in MRI contrast enhancement and vasogenic edema. Responses to this regimen, as defined by a de...

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Autores principales: de Groot, John F., Fuller, Gregory, Kumar, Ashok J., Piao, Yuji, Eterovic, Karina, Ji, Yongjie, Conrad, Charles A.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940588/
https://www.ncbi.nlm.nih.gov/pubmed/20167811
http://dx.doi.org/10.1093/neuonc/nop027
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author de Groot, John F.
Fuller, Gregory
Kumar, Ashok J.
Piao, Yuji
Eterovic, Karina
Ji, Yongjie
Conrad, Charles A.
author_facet de Groot, John F.
Fuller, Gregory
Kumar, Ashok J.
Piao, Yuji
Eterovic, Karina
Ji, Yongjie
Conrad, Charles A.
author_sort de Groot, John F.
collection PubMed
description Patients with recurrent malignant glioma treated with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), alone or in combination with irinotecan have had impressive reductions in MRI contrast enhancement and vasogenic edema. Responses to this regimen, as defined by a decrease in contrast enhancement, have led to significant improvements in progression-free survival rates but not in overall survival duration. Some patients for whom this treatment regimen fails have an uncharacteristic pattern of tumor progression, which can be observed radiographically as an increase in hyperintensity on T2-weighted or fluid-attenuated inverse recovery (FLAIR) MRI. To date, there have been no reports of paired correlations between radiographic results and histopathologic findings describing the features of this aggressive tumor phenotype. In this study, we correlate such findings for 3 illustrative cases of gliomas that demonstrated an apparent phenotypic shift to a predominantly infiltrative pattern of tumor progression after treatment with bevacizumab. Pathologic examination of abnormal FLAIR areas on MRI revealed infiltrative tumor with areas of thin-walled blood vessels, suggesting vascular “normalization,” which was uncharacteristically adjacent to regions of necrosis. High levels of insulin-like growth factor binding protein-2 and matrix metalloprotease-2 expression were seen within the infiltrating tumor. In an attempt to better understand this infiltrative phenotype associated with anti-VEGF therapy, we forced a highly angiogenic, noninvasive orthotopic U87 xenograft tumor to become infiltrative by treating the mice with bevacizumab. This model mimicked many of the histopathologic findings from the human cases and will augment the discovery of alternative or additive therapies to prevent this type of tumor recurrence in clinical practice.
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spelling pubmed-29405882011-03-01 Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice de Groot, John F. Fuller, Gregory Kumar, Ashok J. Piao, Yuji Eterovic, Karina Ji, Yongjie Conrad, Charles A. Neuro Oncol Basic and Translational Investigations Patients with recurrent malignant glioma treated with bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), alone or in combination with irinotecan have had impressive reductions in MRI contrast enhancement and vasogenic edema. Responses to this regimen, as defined by a decrease in contrast enhancement, have led to significant improvements in progression-free survival rates but not in overall survival duration. Some patients for whom this treatment regimen fails have an uncharacteristic pattern of tumor progression, which can be observed radiographically as an increase in hyperintensity on T2-weighted or fluid-attenuated inverse recovery (FLAIR) MRI. To date, there have been no reports of paired correlations between radiographic results and histopathologic findings describing the features of this aggressive tumor phenotype. In this study, we correlate such findings for 3 illustrative cases of gliomas that demonstrated an apparent phenotypic shift to a predominantly infiltrative pattern of tumor progression after treatment with bevacizumab. Pathologic examination of abnormal FLAIR areas on MRI revealed infiltrative tumor with areas of thin-walled blood vessels, suggesting vascular “normalization,” which was uncharacteristically adjacent to regions of necrosis. High levels of insulin-like growth factor binding protein-2 and matrix metalloprotease-2 expression were seen within the infiltrating tumor. In an attempt to better understand this infiltrative phenotype associated with anti-VEGF therapy, we forced a highly angiogenic, noninvasive orthotopic U87 xenograft tumor to become infiltrative by treating the mice with bevacizumab. This model mimicked many of the histopathologic findings from the human cases and will augment the discovery of alternative or additive therapies to prevent this type of tumor recurrence in clinical practice. Oxford University Press 2010-03 2010-01-06 /pmc/articles/PMC2940588/ /pubmed/20167811 http://dx.doi.org/10.1093/neuonc/nop027 Text en © The Author(s) 2010. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic and Translational Investigations
de Groot, John F.
Fuller, Gregory
Kumar, Ashok J.
Piao, Yuji
Eterovic, Karina
Ji, Yongjie
Conrad, Charles A.
Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title_full Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title_fullStr Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title_full_unstemmed Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title_short Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
title_sort tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice
topic Basic and Translational Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940588/
https://www.ncbi.nlm.nih.gov/pubmed/20167811
http://dx.doi.org/10.1093/neuonc/nop027
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