P01.12 Brain Necrosis in Patients With Metastatic Lung and Breast Cancer Successfully Treated With Bevacizumab

Abstract

Patients (pts) develop brain radionecrosis (BRN) as a result of radiation therapy for brain tumors or metastatic brain lesions. This is seen more often now with the use of stereotactic radiosurgery (SRS). BRN is characterized by an increase in permeability and disruption of the blood brain barrier (BBB). The mechanism of BRN is currently unknown, however it is hypothesized that there is an inflammatory reaction of the local tissue to radiation which results in a continuous process involving endothelial cell dysfunction. This leads to tissue hypoxia and increased vascular endothelial growth factor (VEGF) which in turn causes capillary leakage, progressive BBB dysfunction, and cerebral edema. There are currently no standard treatment options for BRN. Bevacizumab (BEV), a humanized monoclonal antibody with action against VEGF, has recently been used in some reports for the treatment of BRN. BEV essentially blocks VEGF from reaching its targets on the endothelium, thus making it an interesting treatment modality for BRN. We identified BRN in 15 pts with brain metastasis treated with SRS at our institution (14 diagnosed with lung cancer and one with breast cancer). We assessed the efficacy and safety of BEV for the treatment of BRN. A demographic review was conducted, analyzing pts’s age, sex, ethnicity, etc. We evaluated the BEV dose, dosing frequency, number of treatments received, medication-related adverse effects (AE), and clinical benefit. Brain imaging, mainly MRI and PET scan, were completed pre-treatment and after four cycles of therapy to evaluate the efficacy of BEV. Pts who exhibited clinical benefit, defined as complete response (CR), partial response (PR), or stable disease (SD), received an additional four cycles of treatment. The median age was 65y (range 49-78y) and 9/14 (64%) pts were female. Clinical benefit was achieved in 13/15 (87%) pts. Pts experienced improvement of cognitive function, headaches, weakness and other symptoms. MRIs showed improvement in edema and a reduction or stabilization of the brain lesions. The most frequent dosing regimen administered was 10 mg/kg of BEV every two weeks and the median number of cycles given was eight cycles (1-12). Treatment with BEV was well tolerated with eight pts (53%) experiencing BEV-related grade two or less AE including hypertension (21%), proteinuria (14%), thrombocytopenia (7%) and mild nose bleeds (7%). There were no Grade 3-5 AE. This study demonstrates that there is a clinical benefit when administering BEV for the treatment of BRN in lung cancer pts with metastatic brain lesions. BEV was well tolerated and had an acceptable safety profile.