SURG-19. RE-PURPOSING DEEP BRAIN STIMULATORS AS ELECTRIC FIELD THERAPY (EFT) AS TREATMENT FOR GLIOBLASTOMA

Abstract

Abstract INTRODUCTION Though alternating electric field therapy (EFT) for glioblastoma received FDA approval, biophysical modeling suggests that field strength generated by scalp electrodes may not sufficiently extend to deep, subcortical regions. Objective: We explore the anti-tumor activity of electric field (EF) generated by electrode directly implanted into glioblastomas, with the goal of repurposing deep brain stimulators as a therapeutic platform. Method: Laboratory characterization and murine modeling Result: In vitro, activation of leads of a deep brain stimulator induced tumoricidal activity within the region encompassed by the EF. To further characterized this tumoricidal activity, a customized two-electrode array was designed and fabricated to allow study of glioblastoma cells seeded at the center of the EF. Consistent with the observations made using the deep brain stimulator electrode, electric field therapy (EFT) induced both necrosis and apoptosis of glioblastoma cells. To characterize this effect in vivo, a four-electrode array was designed and fabricated such that tumor cells can be implanted through a center channel equidistant the electrodes. Mice were implanted with this array, followed by luciferase labelled murine glioblastomas through the center channel. After tumor engravement, mice were randomized to EFT or placebo. EFT was associated with significant diminishment of tumor growth (measured by bio- bioluminescence) and prolonged survival. Analysis of brain sections following EFT showed a notable increase in peri-tumoral microglia accumulation, suggesting potential of EFT as an immune-modulation platform. CONCLUSION Our results suggest therapeutic potential for repurposing of deep brain stimulator as glioblastoma therapy, with opportunities for therapeutic enhancement through novel electrode design and stimulation parameter modulation.