Iatrogenic cerebral radiation necrosis

Cerebral radiation necrosis is the most serious late reaction to high doses of ionising radiation to the brain, and its treatment is generally unsatisfactory. We present a patient who developed cerebral radiation necrosis after protracted fluoroscopy during repeated embolisations of an extracranial arteriovenous malformation. Treatment with bevacizumab (a humanised murine monoclonal antibody against vascular endothelial growth factor) was followed by neurological and radiological improvements.

NCMP-01. THE ROLE OF VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR INHIBITORS IN PREVENTING CEREBRAL RADIATION NECROSIS: A RETROSPECTIVE COHORT STUDY

INTRODUCTION Radiation necrosis (RN) is a potential complication after radiation therapy to primary brain tumors and brain metastases. The pathophysiology of RN is not well understood but it is hypothesized that vascular endothelial growth factor (VEGF) plays an important role. Bevacizumab, a monoclonal antibody against VEGF-A, is often successful in the management of RN. The objective of this study is to assess whether VEGF receptor (VEGFR) inhibitors, a group of oral tyrosine kinase inhibitors (TKIs), can prevent or reverse cerebral radiation necrosis METHODS We retrospectively studied a cohort of 102 patients with renal cell carcinoma (RCC) and brain metastases seen at The Ohio State University James Cancer Center between 01/01/2011 and 04/30/2019. We identified those who developed RN and analyzed the temporal relationship between the use of VEGFR TKIs and the development of RN. RESULTS The cumulative incidence of RN in our cohort is 13.7% after radiation treatments that included LINAC-based stereotactic radiosurgery, fractionated stereotactic radiotherapy, or Gamma Knife radiosurgery. There was no statistically significant difference in the cumulative incidence of RN between patients taking TKIs and patients who were off TKIs (9.9% and 11.5% respectively, p= 0.741). The median time to development of RN was only numerically shorter in patients taking TKIs (151 versus 315 days, p=0.315). One patient developed RN after stopping cabozantinib. Three other patients developed RN while on cabozantinib. Two patients developed RN while on pazopanib, and 3 patients developed RN while on sunitinib. One patient was started on axitinib during active RN without significant improvement subsequently. CONCLUSIONS VEGFR TKIs do not consistently prevent or reverse cerebral radiation necrosis and do not seem to have the efficacy that bevacizumab has against RN.

Cerebral Radiation Necrosis Masquerading as Recurrent, High-Grade Meningioma: A Case Report

Background: Cerebral radiation necrosis (CRN) is a complication caused by radiation therapy (RT) used for treating high-grade intracranial neoplasms. It is essential to be aware of this condition as it can be frequently mistaken for tumor recurrence. Herein, we report a case of misdiagnosis of CRN in a young male, which has heavily influenced his clinical history.Case Presentation: We report a 25-year-old male diagnosed with right frontal convexity meningioma based on computerized tomography (CT)/magnetic resonance imaging (MRI). The operation achieved a macroscopically complete tumor resection. The histopathology was an atypical meningioma. Accordingly, the patient received RT. The patient reported new-onset of generalized seizures and worsening of left hemiparesis three months after completion of RT. MRI showed abnormal peripheral enhancement in the right frontal region involving the genu of the corpus callosum and extensive brain edema. Magnetic resonance spectrometry (MRS) changes were suggestive of tumor recurrence. The patient underwent surgery with total resection of the lesion. The histopathology was CRN without evidence of tumor recurrence. Due to refractory progressive brain edema, the patient’s clinical status deteriorated until he expired.Conclusion: CRN carries morbidity and mortality as a complication from brain irradiation. There is no single modality that can reliably distinguish CRN from recurrent tumor. Therefore, a multimodality approach highly recommended.

Connexin43 Expression and Associated Chronic Inflammation Presages the Development of Cerebral Radiation Necrosis

Cerebral radiation necrosis (CRN) is a delayed complication of radiosurgery that can result in severe neurological deficits. The biological changes leading to necrotic damage may identify therapeutic targets for this complication. Connexin43 expression associated with chronic inflammation may presage the development of CRN. A mouse model of delayed CRN was used. The left hemispheres of adult female mice were irradiated with single-fraction, high-dose radiation using a Leksell Gamma Knife. The brains were collected 1 and 4 days, and 1–3 weeks after the radiation. The expression of connexin43, interleukin-1β (IL-1β), GFAP, isolectin B-4, and fibrinogen was evaluated using immunohistochemical staining and image analysis. Compared with the baseline, the area of connexin43 and IL-1β staining was increased in ipsilateral hemispheres 4 days after radiation. Over the following 3 weeks, the density of connexin43 gradually increased in parallel with progressive increases in GFAP, isolectin B-4, and fibrinogen labeling. The overexpression of connexin43 in parallel with IL-1β spread into the affected brain regions first. Further intensified upregulation of connexin43 was associated with escalated astrocytosis, microgliosis, and blood-brain barrier breach. Connexin43-mediated inflammation may underlie radiation necrosis and further investigation of connexin43 hemichannel blockage is merited for the treatment of CRN.

NCMP-15. BEVACIZUMAB FOR THE TREATMENT OF CEREBRAL RADIATION NECROSIS: A RETROSPECTIVE COHORT STUDY

BACKGROUND Cerebral radiation necrosis (RN) is a critical complication of radiotherapy for brain tumors. Treatment with corticosteroids provides suboptimal symptom relief, and may have considerable side effects. Small-scale studies support the use of bevacizumab, but systematic data from clinical practice on its efficacy and toxicity remain scarce. METHODS In this retrospective cohort study, we included consecutive patients with symptomatic RN that underwent treatment with bevacizumab in our academic neuro-oncology clinic. RN was diagnosed based on imaging, histology or both. The primary outcomes were reported neurological improvement during follow-up, the duration of response, the reported improvement on MRI, and radiological outcome according to RANO criteria. Other outcomes included reduction of dexamethasone dose and the occurrence of adverse events. RESULTS Of the 37 included patients (39 RN-episodes), the majority had a glioblastoma (n = 22) or other diffuse glioma (8), followed by brain metastases (4) or other (3). Clinical response was reported in 17 RN-episodes (43.6%) and lasted for a median of 13 weeks (IQR 6–32 weeks). Radiological improvement during follow-up was reported in 29 RN-episodes (80.6%). RANO-defined radiological responses included 1 complete response (3.4%), 7 partial responses (24.1%), 1 minor response (3.4%) and 17 stable disease (58.6%). In total, 36 adverse events occurred, most commonly venous thrombo-embolism, hypertension and dyspnea, with 8 grade III-IV complications and 2 deaths (grade V) which were possibly related to bevacizumab. Of 32 patients on dexamethasone, 9 (28.1%) had completely stopped its use at treatment cessation. CONCLUSION This observational study confirms that patients with cerebral RN can benefit both clinically and radiologically from bevacizumab treatment in a real-life clinical setting, although our results are more modest than previous literature suggests. The high prevalence of – sometimes severe – adverse events should be weighed against the possible clinical benefit when counselling patients about this treatment option.