EXTH-65. AS1411 ENHANCES CYTOTOXICITY OF SapC-DOPS VIA SURFACE PHOSPHATIDYLSERINE ELEVATION IN GLIOBLASTOMA

Abstract

Brain metastasis (BM) are the most common type of brain tumor with an estimated incidence of 200,000-400,000/yr. in the US alone. BM are also the most common indication for stereotactic radiosurgery (SRS). However, while SRS is highly effective in achieving local control, the incidence of both local recurrence and radiation necrosis (RN) is increasing as treatment for primary systemic cancers improves. Among the challenges at the time of apparent imaging recurrence is differentiating "true" recurrence of BM from RN. Since conventional imaging is not always reliable for this, many patients must undergo surgical biopsy or resection due to this uncertainty. Here, we demonstrate the utility of the novel biomarker Vanin-2 (VNN2) combined with expression of MHC Class II molecule HLA-DR on CD14+ cells in order to differentiate recurrent BM from RN. Our preliminary data indicate that presence of Mo-MDSC is significantly increased in BM compared to RN (49% vs 4%, p=0.005). In contrast, VNN2 expression on CD14+ in BM is decreased compared to RN (4.3% vs 36%, p=0.02). In order to further decrease overlap between outliers in each group of patients, we define the ratio of HLA-DR expression to VNN2 expression on CD14+ cells from as the DR-VNN Index or DVI. While a DVI >1 is considered BM (average= 15.5), a DVI<1 is considered RN (Average 0.07). This increases the receiver operator curve (ROC) and thus the reliability of the biomarker. These results suggest that the novel biomarker VNN2 in conjunction with HLA-DRneg/low on CD14+cells, could be useful to differentiate BM from RN using a minimally invasive blood sample. Thus, the DVI has the potential to serve as an inexpensive and non-invasive biomarker in helping to manage clinical care. Further studies are indicated.