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Erschienen in: Journal of Neuro-Oncology 1/2017

19.04.2017 | Laboratory Investigation

Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation

verfasst von: Chong Duan, Carlos J. Perez-Torres, Liya Yuan, John A. Engelbach, Scott C. Beeman, Christina I. Tsien, Keith M. Rich, Robert E. Schmidt, Joseph J. H. Ackerman, Joel R. Garbow

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2017

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Abstract

Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4–12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment. After treatment, both post-contrast T1-weighted and T2-weighted image-derived lesion volumes decreased (P < 0.001), while the lesion volumes for the control group increased. The abnormally high apparent diffusion coefficient (ADC) for RN also returned to the ADC range for normal brain following treatment (P < 0.001). However, typical RN pathology was still present histologically. Large areas of focal calcification were observed in ~50% of treated mouse brains. Additionally, VEGF and hypoxia-inducible factor 1-alpha (HIF-1α) were continually upregulated in both the anti-VEGF and control groups. Despite improvements observed radiographically following anti-VEGF treatment, lesions were not completely resolved histologically. The subsequent calcification and the continued upregulation of VEGF and HIF-1α merit further preclinical/clinical investigation.
Literatur
2.
Zurück zum Zitat Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy-and chemotherapy-induced necrosis of the brain after treatment 1. Radiology 217:377–384CrossRefPubMed Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy-and chemotherapy-induced necrosis of the brain after treatment 1. Radiology 217:377–384CrossRefPubMed
3.
Zurück zum Zitat Rahmathulla G, Marko NF, Weil RJ (2013) Cerebral radiation necrosis: a review of the pathobiology, diagnosis and management considerations. J Clin Neurosci 20:485–502CrossRefPubMed Rahmathulla G, Marko NF, Weil RJ (2013) Cerebral radiation necrosis: a review of the pathobiology, diagnosis and management considerations. J Clin Neurosci 20:485–502CrossRefPubMed
5.
Zurück zum Zitat Glantz MJ, Burger PC, Friedman AH et al (1994) Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 44:2020–2020CrossRefPubMed Glantz MJ, Burger PC, Friedman AH et al (1994) Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 44:2020–2020CrossRefPubMed
8.
Zurück zum Zitat Torcuator R, Zuniga R, Mohan YS et al (2009) Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 94:63–68CrossRefPubMed Torcuator R, Zuniga R, Mohan YS et al (2009) Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 94:63–68CrossRefPubMed
9.
Zurück zum Zitat Bölke E, Nawatny J, Hoffmann TK et al (2011) Bevacizumab as a treatment option for radiation-induced cerebral necrosis. Strahlenther Onkol 187:135–139CrossRefPubMed Bölke E, Nawatny J, Hoffmann TK et al (2011) Bevacizumab as a treatment option for radiation-induced cerebral necrosis. Strahlenther Onkol 187:135–139CrossRefPubMed
10.
11.
Zurück zum Zitat Scappaticci FA, Fehrenbacher L, Cartwright T et al (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180. doi:10.1002/jso.20301 CrossRefPubMed Scappaticci FA, Fehrenbacher L, Cartwright T et al (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180. doi:10.​1002/​jso.​20301 CrossRefPubMed
12.
Zurück zum Zitat Abrams DA, Hanson JA, Brown JM et al (2015) Timing of surgery and bevacizumab therapy in neurosurgical patients with recurrent high grade glioma. J Clin Neurosci 22:35–39CrossRefPubMed Abrams DA, Hanson JA, Brown JM et al (2015) Timing of surgery and bevacizumab therapy in neurosurgical patients with recurrent high grade glioma. J Clin Neurosci 22:35–39CrossRefPubMed
13.
Zurück zum Zitat Clark AJ, Butowski NA, Chang SM et al (2011) Impact of bevacizumab chemotherapy on craniotomy wound healing: Clinical article. J Neurosurg 114:1609–1616CrossRefPubMed Clark AJ, Butowski NA, Chang SM et al (2011) Impact of bevacizumab chemotherapy on craniotomy wound healing: Clinical article. J Neurosurg 114:1609–1616CrossRefPubMed
14.
16.
Zurück zum Zitat Furuse M, Kawabata S, Kuroiwa T, Miyatake S-I (2010) Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases. J Neurooncol 102:471–475. doi:10.1007/s11060-010-0333-3 CrossRefPubMed Furuse M, Kawabata S, Kuroiwa T, Miyatake S-I (2010) Repeated treatments with bevacizumab for recurrent radiation necrosis in patients with malignant brain tumors: a report of 2 cases. J Neurooncol 102:471–475. doi:10.​1007/​s11060-010-0333-3 CrossRefPubMed
21.
23.
25.
Zurück zum Zitat Yoritsune E, Furuse M, Kuwabara H et al (2014) Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis. J Radiat Res (Tokyo) 55:803–811. doi:10.1093/jrr/rru017 CrossRef Yoritsune E, Furuse M, Kuwabara H et al (2014) Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis. J Radiat Res (Tokyo) 55:803–811. doi:10.​1093/​jrr/​rru017 CrossRef
Metadaten
Titel
Can anti-vascular endothelial growth factor antibody reverse radiation necrosis? A preclinical investigation
verfasst von
Chong Duan
Carlos J. Perez-Torres
Liya Yuan
John A. Engelbach
Scott C. Beeman
Christina I. Tsien
Keith M. Rich
Robert E. Schmidt
Joseph J. H. Ackerman
Joel R. Garbow
Publikationsdatum
19.04.2017
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2017
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2410-3

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