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Bevacizumab in the treatment of radiation injury for children with central nervous system tumors

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Abstract

Purpose

Radiation-induced injury is a well-described toxicity in children receiving radiation therapy for tumors of the central nervous system. Standard therapy has historically consisted primarily of high-dose corticosteroids, which carry significant side effects. Preclinical models suggest that radiation necrosis may be mediated in part through vascular endothelial growth factor (VEGF) overexpression, providing the rationale for use of VEGF inhibitors in the treatment of CNS radiation necrosis. We present the first prospective experience examining the safety, feasibility, neurologic outcomes, and imaging characteristics of bevacizumab therapy for CNS radiation necrosis in children.

Methods

Seven patients between 1 and 25 years of age with neurologic deterioration and MRI findings consistent with radiation injury or necrosis were enrolled on an IRB-approved pilot feasibility study. Patients received bevacizumab at a dose of 10 mg/kg intravenously every 2 weeks for up to 6 total doses.

Results

Five patients (83%) were able to wean off corticosteroid therapy during the study period and 4 patients (57%) demonstrated improvement in serial neurologic exams. All patients demonstrated a decrease in T1-weighted post-gadolinium enhancement on MRI, while 5 (71%) showed a decrease in FLAIR signal. Four patients developed a progressive disease of their underlying tumor during bevacizumab therapy.

Conclusions

Our experience lends support to the safety and feasibility of bevacizumab administration for the treatment of radiation necrosis for appropriately selected patients within the pediatric population.

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Acknowledgments

Support for this study was provided by Genentech, Inc. Genentech US Drug Safety, 1 DNA Way Mailstop 258A, South San Francisco, CA 94080.

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Authors and Affiliations

  1. Center for Cancer and Blood Disorders, Children’s Hospital Colorado, B-115, 13123 East 16th Avenue, Aurora, CO, 80045, USA

    Nathan A. Dahl, Nicholas K. Foreman, Melissa Widener & Margaret E. Macy

  2. Morgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Nathan A. Dahl & Nicholas K. Foreman

  3. Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA

    Arthur K. Liu

  4. Department of Radiology, Children’s Hospital Colorado, Aurora, CO, USA

    Laura Z. Fenton

Authors
  1. Nathan A. Dahl
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  2. Arthur K. Liu
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  3. Nicholas K. Foreman
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  4. Melissa Widener
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  5. Laura Z. Fenton
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  6. Margaret E. Macy
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Corresponding author

Correspondence to Margaret E. Macy.

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Dahl, N.A., Liu, A.K., Foreman, N.K. et al. Bevacizumab in the treatment of radiation injury for children with central nervous system tumors. Childs Nerv Syst 35, 2043–2046 (2019). https://doi.org/10.1007/s00381-019-04304-y

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  • DOI: https://doi.org/10.1007/s00381-019-04304-y

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