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Logo of neuroncolAboutAuthor GuidelinesEditorial BoardNeuro-Oncology
 
Neuro Oncol. 2017 January; 19(Suppl 1): i12.
Published online 2017 March 2. doi:  10.1093/neuonc/now293.043
PMCID: PMC5358619

PP43. THE EFFICACY AND MECHANISM OF THERAPEUTIC STIMULATING ELECTRODES IN GLIOBLASTOMA MULTIFORME

Abstract

INTRODUCTION: In light of the outcomes of the Phase III trials of Tumour Treating Fields (TTFields) in both primary and recurrent adult Glioblastoma multiforme (GBM), a new treatment modality has emerged. TTFields are low intensity (1-3V/cm), intermediate frequency (200kHz) alternating electric fields delivered throughout the brain via external attached electrodes. Overall, TTFields have been found to benefit patients when administered as both a monotherapy and combinational therapy with Temozolomide. TTFields efficacy is largely dependent upon patient compliance with the external power and delivery systems, while effective voltage intensity is limited by resistance from the skin, subcutaneous tissues and skull. Here we present investigations into the application of deep brain stimulation (DBS) electrodes as a novel delivery method of therapeutic electromagnetic fields to high grade brain tumours as an internalised system. METHODS: Medtronic DBS electrodes were inserted into standard cell culture flasks and to deliver electric fields over a multitude of voltages and frequencies to a panel of primary, adult and paediatric GBM cell lines. Cell viability was analysed with Presto Blue assay and gene expression was assessed with quantitative RT-PCR. Cell cycle analysis was undertaken through FACS. The synergistic effects of electric fields and mitosis-specific targeting agents was also assessed. RESULTS: DBS electric fields negatively effects cell viability over a range of GBM cell lines (commercial and primary low passage) in a voltage-dependent manner. Cell viability was reduced by up to 70% and 74% in voltage-dependent manner over the range of voltages (0V to 10V) for 7 days - U87 cells (Two-way ANOVA, p=0.0014) and SF188 cells (Two-way ANOVA, p=0.0001). Cell counts were undertaken of treated U87 and SF188 flasks with a reduction of 93% and 82% respectively, with a greatest reduction in proportion of cells within close proximity to the DBS electrode. We examine synergistic effects with mitotic inhibitor agents. CONCLUSIONS: Implantable DBS electrodes have potential as a novel therapeutic strategy for the treatment of brain tumours. Electric fields delivered through DBS electrodes demonstrate anti-proliferative effects on GBM cell lines in a dose-dependent manner. This effect is actualised at frequencies substantially lower than those utilised by NovoTTF therapy and may represent a different treatment paradigm e.g. interference with ion channels. Impact: Proof-of-concept of electric fields treatment has been demonstrated by the OptuneTM system, however limitations of patient adherence persists, but implantable DBS electrodes may address these issues.


Articles from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Oxford University Press