Single-shot bevacizumab for cerebral radiation injury

Abstract

Background: Cerebral radiation injury, including subacute radiation reactions and later stage radiation necrosis, is a severe side effect of brain tumor radiotherapy. A protocol of four infusions of the monoclonal antibody bevacizumab has been shown to be a highly effective treatment. However, bevacizumab is costly and can cause severe complications including thrombosis, bleeding and gastrointestinal perforations.

Methods: We performed a retrospective analysis of patients treated in our clinic for cerebral radiation injury who received only a singular treatment with bevacizumab. Single-shot was defined as a singular administration of bevacizumab without a second administration during an interval of at least 6 weeks.

Results: We identified 11 patients who had received a singular administration of bevacizumab to treat cerebral radiation injury. Prior radiation had been administered to treat gliomas (ten patients) or breast cancer brain metastases (one patient). 9 of 10 patients with available MRIs showed a marked reduction of edema at first follow-up. Discontinuation of Dexamethasone was possible in 6 patients and a significant dose reduction could be achieved in all other patients. One patient developed pulmonary artery embolism 2 months after bevacizumab administration. The median time to treatment failure of any cause was 3 months.

Conclusions: Single-shot bevacizumab therefore has meaningful activity in cerebral radiation injury, but durable control is rarely achieved. In patients where a complete protocol of four infusions with bevacizumab is not feasible due to medical contraindications or lack of reimbursement, single-shot bevacizumab treatment may be considered.

Keywords: Bevacizumab; Dexamethasone; Edema; Radiation necrosis; Side effect.

Fig. 1

MRI scans of a 34 year old patient with IDH-mutated astrocytoma. a MRI revealed a small recurrent tumor adjacent to the dorsal resection cavity with small surrounding edema. b The patient was treated with re-radiation therapy with 35 Gy and concomitant temozolomide. First MRI after the treatment showed an increase of contrast enhancement and edema which was diagnosed as radiation necrosis. c Therapy with 8 mg of dexamethasone did neither improve the MRI nor the clinical symptoms and bevacizumab 7.5 mg/kg was administered as a single-shot. d First scan one month later displayed a marked reduction in contrast enhancement and of the edema. Treatment with dexamethasone could be stopped. The follow up 3 months later was stable (not shown)

Fig. 2

MRI scans of a 33 year old patient with IDH-wildtype glioblastoma. First (a) and second (b) MRI after resection and radiation therapy of recurrent glioblastoma showed not signs of tumor progression. Dexamethasone was started because of clinical deterioration before the third control (c) which showed a substantial increase in contrast enhancement and edema which were interpreted as late radiation necrosis. Bevacizumab 7.5 mg/kg was administered as a single-shot. d First scan 1.5 months later displayed a marked reduction of the edema while there was only a minor reduction of contrast enhancement. Diagnosis was changed from radiation necrosis to recurrent tumor

Fig. 3

Time to treatment failure. The swimmer plot shows the course of the individual patients labeled at the left side. The radiological diagnosis is indicated by color-coded dots (yellow: MRI, orange: MRI and MR-perfusion, purple: PET). The color-coded diamonds indicate the treatment failure of the single-shot bevacizumab (green: treatment of recurrent edema with corticosteroids, blue: treatment of recurrent edema with bevacizumab, blue border: resumed bevacizumab as the symptoms did not completely resolve, red: recurrent tumor, black: death of the patient because of recurrent tumor). Median time from single-shot to time of treatment failure of any cause) was three months