Bevacizumab for symptomatic cerebral radiation necrosis after radiation of high-grade glioma or brain metastases – when and for whom?

Cerebral radiation necrosis (CRN) is a serious complication of high-dose radiotherapy in patients with high-grade glioma (HGG) and brain metastases (BM). Approximately half of the patients with radiological CRN develop debilitating neurological symptoms that significantly affect their neurocognitive functioning, performance status, and health-related quality of life (HRQoL), requiring treatment. While corticosteroids are the standard first-line treatment for symptomatic CRN (sCRN), they have considerable drawbacks, including limited efficacy, severe side effects affecting various organ systems, and interference with concurrent therapies, such as immunotherapy. Prolonged corticosteroid use can lead to adrenal insufficiency and dependence on hormone replacement. Bevacizumab has been shown to reduce the contrast-enhancing CRN lesion on MRI and surrounding edema, improving clinical outcomes in most patients. However, most evidence comes from smaller, single-center, retrospective studies focusing on short-term radiological and clinical outcomes, typically in patients already treated with corticosteroids. Information on the optimal timing of bevacizumab administration and its long-term effects and impact on patient-reported outcomes, including HRQoL, is lacking. These limitations prevented the adoption of first-line bevacizumab treatment for sCRN in international guidelines and insurance coverage policies. A well-powered prospective clinical trial comparing the clinical and cost-effectiveness of first-line bevacizumab versus corticosteroids in HGG and BM patients is essential.