Favorable outcome with bevacizumab after poor outcome with steroids in a patient with temporal lobe and brainstem radiation necrosis

Abstract

Cerebral radiation necrosis is a severe complication of radiotherapy [1]. It is usually treated with steroids, but many patients relapse when steroids are discontinued or suffer from steroid side effects [2]. Alternative treatments include aspirin, anticoagulants and hyperbaric oxygen, but their efficacy remains modest [2]. Bevacizumab, a humanized murine monoclonal antibody against VEGF, has been suggested as a promising new strategy to treat cerebral radiation necrosis [3–7]. Nevertheless, data concerning the use of bevacizumab to treat radiation necrosis complicating radiation for head-and-neck cancer remains scarce. Furthermore, the relative efficacy of bevacizumab over steroids is unknown. We report a patient who developed a brainstem radiation necrosis 1 year after radiotherapy for a nasopharyngeal carcinoma and a temporal lobe radiation necrosis 3 years later. The brainstem radiation necrosis was treated with steroids only. Despite this treatment, it resulted in severe neurological impairment. The temporal lobe radiation necrosis was treated with bevacizumab and resolved rapidly. A 38-year-old woman with a T4N2M0 undifferentiated nasopharyngeal carcinoma was treated with cisplatin and conformational radiotherapy (66 Gy), followed by an additional three cycles of cisplatin and fluorouracil. The brainstem and left temporal lobe received up to 62 Gy. One year after completing radiotherapy, she developed a progressive right-sided hemiparesis. An MRI showed necrotic contrast-enhancing lesions in the pons and in the medulla suggestive of brainstem radiation necrosis (Fig. 1). The patient was treated with prednisolone (1 mg/kg). Contrast enhancement of the lesion on MRI diminished slowly but persisted after 6 months of treatment (Fig. 1). However, the neurological condition of the patient worsened and she became bedridden. Steroid treatment was responsible for many side effects, including diabetes, 10 kg weight gain and corticosteroid myopathy. Because of clinical inefficacy and side effects, the steroids were stopped 18 months after their initiation. The residual contrast enhancement remained stable. During follow-up, three and a half years after completing the radiotherapy, a left temporal lobe radiation necrosis was observed. As the patient had no related symptoms, we decided to observe her for a period of time. After 8 months of follow-up, the patient developed severe headaches. An MRI demonstrated an increase of the left temporal lobe radiation necrosis with vasogenic edema and a mass effect. Perfusion MRI and MRI spectroscopy were consistent with radiation necrosis. Because of the prior inefficacy of steroids, the patient was treated with 5 mg/kg of bevacizumab every other week without steroids. After the first dose, the headaches disappeared. After four doses, near complete resolution of the A. Benoit F. Ducray S. Cartalat-Carel J. Honnorat Hospices Civils de Lyon, Neurologie B, 69394 Lyon, France