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Bevacizumab for Cerebral Radionecrosis: A Single-Center Experience

Published online by Cambridge University Press:  30 May 2022

Seth A. Climans Open the ORCID record for Seth A. Climans [Opens in a new window] ,
Ronald C. Ramos Open the ORCID record for Ronald C. Ramos [Opens in a new window] ,
Paola A. Jablonska ,
David B. Shultz  and
Warren P. Mason
Seth A. Climans*
Affiliation:
Departments of Neurology and Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada Department of Oncology, London Health Sciences Centre, London, Canada
Ronald C. Ramos
Affiliation:
Departments of Neurology and Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada
Paola A. Jablonska
Affiliation:
Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Canada
David B. Shultz
Affiliation:
Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Canada
Warren P. Mason
Affiliation:
Departments of Neurology and Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada
*
Corresponding author: Dr. Seth Climans, Departments of Neurology and Medical Oncology and Hematology, Princess Margaret Cancer Centre, 800 Commissioners Rd E, London, Ontario, Canada, N6A 5W9. Email: seth.climans@lhsc.on.ca
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Abstract:

Background:

Cerebral radionecrosis, a subacute or late effect of radiotherapy, can be debilitating and difficult to treat. Steroids can reduce symptoms, but have significant long-term side effects. Bevacizumab has been shown to reduce edema and other radiologic features associated with radionecrosis and improve patient symptoms. We report our experience using bevacizumab for cerebral radionecrosis.

Methods:

We retrospectively reviewed the charts of all patients treated at our institution with bevacizumab for non-glioma-associated cerebral radionecrosis. We recorded change in symptoms, change in steroids, change in performance status, time to tumor progression, and time to death. We delineated the volume of necrosis pre- and post-bevacizumab on T1-post-gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI scans.

Results:

We identified 15 patients, 8 with brain metastases, 6 with meningioma, and 1 with nasopharyngeal carcinoma. Most received four doses of bevacizumab, 7.5 mg/kg q 3 weeks × 4 doses. Neuroimaging demonstrated a reduced T1 gadolinium-enhancing volume and edema in 14/15 patients (the average reduction in T1-post-gadolinium volume was 3.0 cm3, and average reduction in FLAIR volume was 27.9 cm3). There was no appreciable change in patient performance status. Steroid doses decreased in five of nine patients. There was a high rate (26%) of adverse events, including pulmonary embolism, stroke, and wound dehiscence. The median progression-free survival was 6.5 months.

Conclusion:

Although bevacizumab is commonly prescribed for cerebral radionecrosis, in our retrospective cohort, the clinical benefits were modest and there was significant toxicity.

Résumé :

RÉSUMÉ :

Le bévacizumab et la radionécrose cérébrale : expérience unicentrique.

Contexte :

La radionécrose cérébrale, un effet subaigu ou tardif de la radiothérapie, peut à la fois être débilitante et difficile à traiter. Certes, les stéroïdes peuvent atténuer les symptômes, mais ils produisent d’importants effets indésirables à long terme. Le bévacizumab a démontré son efficacité à diminuer l’œdème et d’autres signes radiologiques associés à la radionécrose, ainsi que l’intensité des symptômes. Il sera donc question dans l’article de l’expérience réalisée dans l’établissement des auteurs sur l’emploi du bévacizumab dans le traitement de la radionécrose cérébrale.

Méthode :

L’étude consistait en un examen rétrospectif des dossiers médicaux de tous les patients traités dans l’établissement en question par le bévacizumab pour de la radionécrose cérébrale associée à d’autres tumeurs que les gliomes. Ont été consignés les changements de symptômes, de stéroïdes et de l’indice de performance; le temps écoulé avant l’évolution de la tumeur et celui avant la mort. Le volume de tissu nécrosé a été mesuré, avant et après l’administration du bévacizumab, par IRM, en T1, après injection de gadolinium, et par la séquence FLAIR (inversion-récupération en suppression de liquide).

Résultats :

L’examen a permis de repérer 15 patients : 8 atteints de métastases au cerveau; 6, d’un méningiome et 1, d’un carcinome du rhinopharynx. La plupart ont reçu 4 doses de bévacizumab, à raison de 7,5 mg/kg, toutes les 3 semaines, pour un total de 4 doses. La neuro-imagerie a révélé une diminution du volume en T1, après l’injection de gadolinium pour l’amélioration du contraste, ainsi que de l’œdème chez 14 patients sur 15 (réduction moyenne du volume en T1, après gadolinium : 3,0 cm3, et selon la séquence FLAIR : 27,9 cm3). Toutefois, aucun changement important de l’indice de performance n’a été observé. Il y a eu une diminution des doses de stéroïdes chez 5 patients sur 9, mais le taux d’événements indésirables, notamment d’embolie pulmonaire, d’accident vasculaire cérébral et de déhiscence de la plaie, associés au médicament était élevé (26 %). Enfin, la période médiane de survie sans évolution était de 6,5 mois.

Conclusion :

Bien que le bévacizumab soit souvent prescrit dans le traitement de la radionécrose cérébrale, les résultats enregistrés dans la cohorte formée en vue de l’analyse rétrospective ont révélé que le médicament produisait peu de bienfaits cliniques et qu’il s’accompagnait d’une toxicité importante.

Keywords

RadiotherapyRadionecrosisBevacizumabBrain metastasisMeningioma
Type
Original Article
Information
Canadian Journal of Neurological Sciences , Volume 50 , Issue 4 , July 2023 , pp. 573 - 578
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

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