Bevacizumab for pediatric radiation necrosis

Author:

Baroni Lorena V123,Alderete Daniel12,Solano-Paez Palma4,Rugilo Carlos5,Freytes Candela2,Laughlin Suzanne6,Fonseca Adriana1,Bartels Ute1,Tabori Uri17,Bouffet Eric1,Huang Annie17,Laperriere Normand8,Tsang Derek S8,Sumerauer David9,Kyncl Martin10,Ondrová Barbora11,Malalasekera Vajiranee S12,Hansford Jordan R121314,Zápotocký Michal1,Ramaswamy Vijay137ORCID

Affiliation:

1. Division of Haematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada

2. Service of Hematology/Oncology, Hospital JP Garrahan, Buenos Aires, Argentina

3. Arthur and Sonia Labatt Brain Tumour Research Centre, Programme in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada

4. Service of Pediatric Oncology, Hospital Infantil Virgen del Rocío, Seville, Spain

5. Service of Diagnostic Imaging, Hospital JP Garrahan, Buenos Aires, Argentina

6. Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON, Canada

7. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

8. Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada

9. Department of Paediatric Haematology and Oncology, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

10. Department of Radiology, University Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech Republic

11. Proton Therapy Center Czech, Prague, Czech Republic

12. Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, Australia

13. Division of Cancer, Murdoch Children’s Research Institute, Melbourne, Australia

14. Department of Paediatrics, University of Melbourne and Monash University, Melbourne, Australia

Abstract

Abstract Background Radiation necrosis is a frequent complication occurring after the treatment of pediatric brain tumors; however, treatment options remain a challenge. Bevacizumab is an anti-VEGF monoclonal antibody that has been shown in small adult cohorts to confer a benefit, specifically a reduction in steroid usage, but its use in children has not been well described. Methods We describe our experience with bevacizumab use for symptomatic radiation necrosis at 5 institutions including patients treated after both initial irradiation and reirradiation. Results We identified 26 patients treated with bevacizumab for symptomatic radiation necrosis, with a wide range of underlying diagnoses. The average age at diagnosis of radiation necrosis was 10.7 years, with a median time between the last dose of radiation and the presentation of radiation necrosis of 3.8 months (range, 0.6-110 months). Overall, we observed that 13 of 26 patients (50%) had an objective clinical improvement, with only 1 patient suffering from significant hypertension. Radiological improvement, defined as reduced T2/fluid-attenuated inversion recovery signal and mass effect, was observed in 50% of patients; however, this did not completely overlap with clinical response. Both early and late radiation necrosis responded equally well to bevacizumab therapy. Overall, bevacizumab was very well tolerated, permitting a reduction of corticosteroid dose and/or duration in the majority of patients. Conclusions Bevacizumab appears to be effective and well-tolerated in children as treatment for symptomatic radiation necrosis and warrants more robust study in the context of controlled clinical trials.

Funder

Meagan’s Walk Foundation Fellowship

The Terry Fox Foundation International Fellowship

Canadian Institutes for Health Research, Garron Family Cancer Centre

Publisher

Oxford University Press (OUP)

Subject

Medicine (miscellaneous)

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