Effectiveness of Bevacizumab for Radiation-Induced Cerebral Necrosis in Children

Abstract

Introduction: Bevacizumab has been reported to effectively reduce cerebral edema caused by radiation therapy. However, only limited data with a short follow-up in tumor patients are available so far. Patients and Methods: Two children suffering from hemorrhage from arteriovenous malformation (AVM) have been treated with stereotactic radiotherapy and developed radiation-induced cerebral edema with deteriorating neurological status despite maximized steroid therapy. Bevacizumab administration at 5 mg/kg body weight was initiated every 2 weeks. Results: Bevacizumab treatment rapidly ameliorated the neurological deficits, malignant edema and prevented catastrophic complications. Corticoid therapy could be reduced and discontinued. However, after 18 months, both patients showed identical or worse neurological status than before bevacizumab therapy. AVM radiation therapy had been successful to completely obliterate AVMs. Discussion: In our limited experience, bevacizumab may be an effective and safe option for rescue therapy for malignant cerebral edema on the basis of radiation-induced necrosis especially in patients who experience rapid deterioration despite corticoid therapy and/or intolerable steroid side effects. Despite the fact that functional improvement could not be achieved in long-term outcome patients significantly stabilized and improved during periods of acute deterioration. In order to determine the long-term effectiveness of bevacizumab further investigation in placebo-controlled studies with a higher number of patients are required.

Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo

“…42,43 There are also anecdotal reports on the use of bevacizumab in subjects with brain AVMs. 44–48 However, efficacy and safety of this therapy in human brain AVMs remain to be determined, and a phase I trial is currently enrolling adult patients with high-grade AVMs (NCT02314377). Our findings suggest the possibility to use anti-Shh treatments as novel therapeutic approach for brain AVMs.…”

Resolution of Radiation-Induced Necrosis in Arteriovenous Malformation with Bevacizumab: A Case Report and Review of Current Literature

“…Williams et al [12] reported improvement in symptoms – including reduction of headaches and increased strength – and a reduction in T2 FLAIR. Preuss et al [13] supplied examples of using bevacizumab in pediatric patients with mixed results. Both the patients experienced marked reduction in T2 FLAIR but with only initial symptom improvement that proved marginal long-term.…”

Supportive care for toxicities in children undergoing radiation therapy

“…Other options include hyperbaric oxygen therapy 19 or bevacizumab, a vascular endothelial growth factor (VEGF)-A inhibitor, in addition to steroids. [20][21][22] In children, bevacizumab can improve serial neurological examinations and permit weaning of corticosteroid therapy in most patients but carries a small risk of serious adverse events. 20,23 Currently, there is insufficient evidence to guide the comparative effectiveness of these alternative therapies.…”

“…Children are prone to significant complications from prolonged corticosteroid use, including Cushingoid features, weight gain, hypertension, insomnia, avascular necrosis, and stunted growth. Other options include hyperbaric oxygen therapy 19 or bevacizumab, a vascular endothelial growth factor (VEGF)‐A inhibitor, in addition to steroids 20‐22 . In children, bevacizumab can improve serial neurological examinations and permit weaning of corticosteroid therapy in most patients but carries a small risk of serious adverse events 20,23 .…”