*Article* **Adrenal Insu**ffi**ciency in Patients with Corticosteroid-Refractory Cerebral Radiation Necrosis Treated with Bevacizumab**

**Martin Voss 1,2,3,4,\*, AbdulAziz Batarfi 5, Eike Steidl 6, Marlies Wagner 6, Marie-Thérèse Forster 7, Joachim P. Steinbach 1,2,3,4, Claus M. Rödel 8, Jörg Bojunga <sup>9</sup> and Michael W. Ronellenfitsch 1,2,3,4**


Received: 27 August 2019; Accepted: 27 September 2019; Published: 3 October 2019

**Abstract:** Cerebral radiation necrosis is a common complication of the radiotherapy of brain tumours that can cause significant mortality. Corticosteroids are the standard of care, but their efficacy is limited and the consequences of long-term steroid therapy are problematic, including the risk of adrenal insufficiency (AI). Off-label treatment with the vascular endothelial growth factor A antibody bevacizumab is highly effective in steroid-resistant radiation necrosis. Both the preservation of neural tissue integrity and the cessation of steroid therapy are key goals of bevacizumab treatment. However, the withdrawal of steroids may be impossible in patients who develop AI. In order to elucidate the frequency of AI in patients with cerebral radiation necrosis after treatment with corticosteroids and bevacizumab, we performed a retrospective study at our institution's brain tumour centre. We obtained data on the tumour histology, age, duration and maximum dose of dexamethasone, radiologic response to bevacizumab, serum cortisol, and the need for hydrocortisone substitution for AI. We identified 17 patients with cerebral radiation necrosis who had received treatment with bevacizumab and had at least one available cortisol analysis. Fifteen patients (88%) had a radiologic response to bevacizumab. Five of the 17 patients (29%) fulfilled criteria for AI and required hormone substitution. Age, duration of dexamethasone treatment, and time since radiation were not statistically associated with the development of AI. In summary, despite the highly effective treatment of cerebral radiation necrosis with bevacizumab, steroids could yet not be discontinued due to the development of AI in roughly one-third of patients. Vigilance to spot the clinical and laboratory signs of AI and appropriate testing and management are, therefore, mandated.

**Keywords:** adrenal insufficiency; Addison's disease; bevacizumab; cerebral radiation necrosis
