Lorena V Baroni1,2,3, Daniel Alderete1,2, Palma Solano-Paez4, Carlos Rugilo5, Candela Freytes2, Suzanne Laughlin6, Adriana Fonseca1, Ute Bartels1, Uri Tabori1,7, Eric Bouffet1, Annie Huang1,7, Normand Laperriere8, Derek S Tsang8, David Sumerauer9, Martin Kyncl10, Barbora Ondrová11, Vajiranee S Malalasekera12, Jordan R Hansford12,13,14, Michal Zápotocký1, Vijay Ramaswamy1,3,7. 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
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.
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.
Authors: Nathan A Dahl; Arthur K Liu; Nicholas K Foreman; Melissa Widener; Laura Z Fenton; Margaret E Macy Journal: Childs Nerv Syst Date: 2019-07-31 Impact factor: 1.475
Authors: Daniel Felix Fleischmann; Johanna Jenn; Stefanie Corradini; Viktoria Ruf; Jochen Herms; Robert Forbrig; Marcus Unterrainer; Niklas Thon; Friedrich Wilhelm Kreth; Claus Belka; Maximilian Niyazi Journal: Radiother Oncol Date: 2019-06-25 Impact factor: 6.280