*3.1. Successful Treatment of a Patient with Cerebral Radiation Necrosis with Subsequent Adrenal Insu*ffi*ciency*

The therapeutic potential to treat radiation necrosis is exemplified by one patient who had received a second course of radiation for a recurrent glioblastoma. The initial diagnosis was established by tumour resection in 2016. First-line therapy consisted of radiation therapy with a cumulative dose of 60 Gy with concomitant and adjuvant temozolomide according to the EORTC26981 trial protocol [20]. Five months after the end of chemotherapy, a recurrent tumour was diagnosed and resected. Afterwards, the tumour cavity was treated by another course of radiotherapy with a cumulative dose of 20 Gy. The patient subsequently experienced a worsening of headaches and epileptic seizures. An MRI scan showed an increase of contrast enhancing lesions with corresponding edema and led to treatment of the putative radio necrosis with 8 mg dexamethasone daily. In the course of further treatment, parts of the contrast-enhancing lesions were resected in order to differentiate between tumour recurrence and radiation necrosis, and dexamethasone treatment could be ceased. Cortisol had not been analysed at this time point. Histology showed mainly necrosis and scar tissue. A follow-up MRI again showed progressive edema and contrast enhancement, so that dexamethasone treatment was started once again at a dose of 8 mg per day (Figure 1A,B). Despite this treatment, a follow-up MRI again showed progressive contrast enhancement (Figure 1C,D). As a potential side effect of the dexamethasone therapy, the patient became increasingly aggressive towards family members. A 18F-FET PET scan was compatible with radiation necrosis and therapy with bevacizumab was started. After two infusions of bevacizumab, MRI already confirmed a significant reduction of both contrast enhancement and cerebral edema (Figure 1E,F). Treatment with dexamethasone could be stopped shortly thereafter, but serum analysis revealed severe AI with 0.7 μg/dL cortisol. Thus, substitution with hydrocortisone was started. After the therapy with bevacizumab and the end of dexamethasone, the belligerence and rate of epileptic seizures had significantly improved.

**Figure 1.** Brain edema and disruption of the blood–brain barrier in an index patient with cerebral radiation necrosis. MRI scans of a 46-year-old patient with glioblastoma of the right parietal lobe (**A**,**C**,**E**): T2 weighted images (WI); (**B**,**D**,**F**): T1 (WI) after intravenous gadolinium). Re-radiation was applied 10 months before the first MRI. (**A**,**B**) MRI shows a non-solid, necrotizing lesion with rim enhancement adjacent to the resection defect with surrounding edema. Due to worsening headache and increased rate of epileptic seizures, dexamethasone was started one month later. (**C**,**D**) the clinical symptoms had declined, yet the MRI shows an increasing extent of the rim-enhancing lesion and of the edema, so therapy with bevacizumab was started one month later. (**E**,**F**) the first follow-up MRI after two infusions of bevacizumab showed a significant reduction of contrast enhancement and edema. Treatment with dexamethasone could be stopped shortly after, but serum analysis revealed an adrenal insufficiency.
