Targeted intraarterial anti-VEGF therapy for medically refractory radiation necrosis in the brain.
J Neurosurg Pediatr
; 15(1): 20-5, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25360851
ABSTRACT
Radiation necrosis (RN) is a serious complication that can occur in up to 10% of brain radiotherapy cases, with the incidence dependent on both dose and brain location. Available medical treatment for RN includes steroids, vitamin E, pentoxifylline, and hyperbaric oxygen. In a significant number of patients, however, RN is medically refractory and the patients experience progressive neurological decline, disabling headaches, and decreased quality of life. Vascular endothelial growth factor (VEGF) is a known mediator of cerebral edema in RN. Recent reports have shown successful treatment of RN with intravenous bevacizumab, a monoclonal antibody for VEGF. Bevacizumab, however, is associated with significant systemic complications including sinus thrombosis, pulmonary embolus, gastrointestinal tract perforation, wound dehiscence, and severe hypertension. Using lower drug doses may decrease systemic exposure and reduce complication rates. By using an intraarterial route for drug administration following blood-brain barrier disruption (BBBD), the authors aim to lower the bevacizumab dose while increasing target delivery. In the present report, the authors present the cases of 2 pediatric patients with cerebral arteriovenous malformations, who presented with medically intractable RN following stereotactic radiosurgery. They received a single intraarterial infusion of 2.5 mg/kg bevacizumab after hyperosmotic BBBD. At mean follow-up duration of 8.5 months, the patients had significant and durable clinical and radiographic response. Both patients experienced resolution of their previously intractable headaches and reversal of cushingoid features as they were successfully weaned off steroids. One of the patients regained significant motor strength. There was an associated greater than 70% reduction in cerebral edema. Intraarterial administration of a single low dose of bevacizumab after BBBD was safe and resulted in durable clinical and radiographic improvements at concentrations well below those required for the typical systemic intravenous route. Advantages over the intravenous route may include higher concentration of drug delivery to the affected brain, decreased systemic toxicity, and a significantly lower cost.
Palavras-chave
AVM = arteriovenous malformation; BBB = blood-brain barrier; BBBD = BBB disruption; RN = radiation necrosis; SRS = stereotactic radiosurgery; VEGF = vascular endothelial growth factor; arteriovenous malformation; bevacizumab; blood-brain barrier disruption; intraarterial chemotherapy; oncology; radiation adverse effect; radiation necrosis; stereotactic radiosurgery
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Lesões por Radiação
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Encéfalo
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Malformações Arteriovenosas Intracranianas
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Radiocirurgia
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Inibidores da Angiogênese
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Fator A de Crescimento do Endotélio Vascular
/
Anticorpos Monoclonais Humanizados
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
Limite:
Child
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Female
/
Humans
Idioma:
En
Revista:
J Neurosurg Pediatr
Assunto da revista:
NEUROCIRURGIA
/
PEDIATRIA
Ano de publicação:
2015
Tipo de documento:
Article