Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiationinduced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy.
Die strahleninduzierte Radionekrose des Gehirns stellt eine schwerwiegende Komplikation der Strahlentherapie dar und tritt bei hohen Gesamtdosen oder hohen fraktionierten Einzeldosen häufiger und früher auf. Es wird vermutet, dass hierfür eine erhöhte Freisetzung von Zytokinen ursächlich ist, die zu einer erhöhten Kapillarpermeabiliät und in der Folge zu einem extrazellulären Ödem führt. Dieser Prozess wird durch die endotheliale Dysfunktion sowie eine Gewebehypoxie weiter verstärkt und kann letztendlich zu einer Nekrose führen. Eine Blockade des vaskulären endothelialen Wachstumsfaktors (vascular endothelial growthfactor; VEGF) könnte diese verstärkte vaskuläre Permeabilität vermindern. Somit könnten pathologische Prozesse umgekehrt, neurologische Ausfallerscheinungen vermindert und ein Fortschreiten der Problematik verhindert werden. Wir präsentieren hier einen Fall einer strahleninduzierten Nekrose, bei dem sich unter Therapie mit einem anti-VEGF Antikörper (Bevacizumab) eine Besserung der neurologischen Zeichen und Symptome in Analogie zu einer MR-morphologischen Abnahme des T2-Signals zeigte. Eine Zusammenschau dieses Falles und der aktuellen verfügbaren Literatur lässt den Schluss zu, dass Bevacizumab eine Behandlungsoption für Patienten mit Symptomen und radiologischen Zeichen einer strahleninduzierten zerebralen Nekrose sein kann.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andisheh B, Brahme A, Bitaraf MA, et al. Clinical and radiobiological advantages of single-dose stereotactic light-ion radiation therapy for large intracranial arteriovenous malformations. Technical note. J Neurosurg 2009;111:919–26.
Azzam EI, Yang Z, Li M, et al. The effect of human cord blood therapy on the intestinal tract of lethally irradiated mice: possible use for mass casualties. Int J Radiat Biol;86:467–75.
Castinetti F, Brue T. [Radiotherapy and radiosurgery of pituitary adenomas]. Presse Med 2009;38:133–9.
Cheung MC, Chan AS, Law SC, et al. Impact of radionecrosis on cognitive dysfunction in patients after radiotherapy for nasopharyngeal carcinoma. Cancer 2003;97:2019–26.
Fokas E, Wacker U, Gross MW, et al. Hypofractionated stereotactic reirradiation of recurrent glioblastomas: a beneficial treatment option after high-dose radiotherapy? Strahlenther Onkol 2009;185:235–40.
Gonzalez J, Kumar AJ, Conrad CA, et al. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 2007;67:323–6.
Gutin PH, Iwamoto FM, Beal K, et al. Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 2009;75:156–63.
Henke G, Paulsen F, Steinbach JP, et al. Hypofractionated reirradiation for recurrent malignant glioma. Strahlenther Onkol 2009;185:113–9.
Henzel M, Hamm K, Sitter H, et al. Comparison of stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neurinomas according to 3-D tumor volume shrinkage and quality of life. Strahlenther Onkol 2009;185:567–73.
Hyakkoku K, Nakajima Y, Izuta H, et al. Thalidomide protects against ischemic neuronal damage induced by focal cerebral ischemia in mice. Neuroscience 2009;159:760–9.
Kang KB, Wang TT, Woon CT, et al. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis. Int J Radiat Oncol Biol Phys 2007;67:888–96.
Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 2010 Apr 15 [Epub ahead of print].
Liu AK, Macy ME, Foreman NK. Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 2009;75:1148–54.
Marks JE, Wong J. The risk of cerebral radionecrosis in relation to dose, time and fractionation. A follow-up study. Prog Exp Tumor Res 1985;29:210–218.
Mizumoto M, Nakayama H, Tokita M, et al. Technical considerations for noncoplanar proton-beam therapy of patients with tumors proximal to the optic nerve. Strahlenther Onkol 2010;186:36–9.
Nikitin KV, Shishkina LV, Pronin IN, et al. [Radiation necrosis after stereotactic radiosurgery for benign glioma]. Zh Vopr Neirokhir Im N N Burdenko 2009:37–42; discussion 42.
Prasanna PG, Uma Devi P. Modification of WR-2721 radiation protection from gastrointestinal injury and death in mice by 2-mercaptopropionylglycine. Radiat Res 1993;133:111–5.
Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 2009;27:1227–34.
Sterzing F, Welzel T, Sroka-Perez G, et al. Reirradiation of multiple brain metastases with helical tomotherapy. A multifocal simultaneous integrated boost for eight or more lesions. Strahlenther Onkol 2009;185:89–93.
Torcuator R, Zuniga R, Loutfi R, et al. Bevacizumab and irinotecan treatment for progressive diffuse brainstem glioma: case report. J Neurooncol 2009;93:409–12.
Torcuator R, Zuniga R, Mohan YS, et al. Initial experience with bevacizumab treatment for biopsy confirmed cerebral radiation necrosis. J Neurooncol 2009;94:63–8.
Tsao MN, Li YQ, Lu G, et al. Upregulation of vascular endothelial growth factor is associated with radiation-induced blood-spinal cord barrier breakdown. J Neuropathol Exp Neurol 1999;58:1051–60.
Williams KJ, Telfer BA, Shannon AM, et al. Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts. Br J Radiol 2008;81 Spec No 1:S21–7.
Wilson CM, Gaber MW, Sabek OM, et al. Radiation-induced astrogliosis and blood-brain barrier damage can be abrogated using anti-TNF treatment. Int J Radiat Oncol Biol Phys 2009;74:934–41.
Wong ET, Huberman M, Lu XQ, et al. Bevacizumab reverses cerebral radiation necrosis. J Clin Oncol 2008;26:5649–50.
Author information
Authors and Affiliations
Corresponding author
Additional information
*Authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Matuschek, C., Bölke, E., Nawatny, J. et al. Bevacizumab as a Treatment Option for Radiation-Induced Cerebral Necrosis. Strahlenther Onkol 187, 135–139 (2011). https://doi.org/10.1007/s00066-010-2184-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-010-2184-4