P17.23 * ALTERNATING ELECTRIC FIELDS (TTFIELDS) FOR TREATING GLIOBLASTOMAS: A MODELLING STUDY ON EFFICACY

Abstract

Tumor Treating Fields (TTFields) were recently approved by the US FDA for the treatment of recurrent glioblastoma multiforme (GBM). They are thought to act by disrupting spindle microtubule arrangement and interfering with cytokinesis through the orientation of polar macromolecules in the direction of impressed alternating electric fields. The magnitude and direction of the electric field in the tumor are crucial factors of treatment efficacy. For this computational study we used a realistic head model previously constructed from MRI data to calculate the electric field distribution in the brain. MRIs with a voxel size of 1x1x1 mm3 were segmented into five different tissue types: scalp, skull, cerebrospinal fluid, gray matter, and white matter. Additionally a virtual lesion was included to simulate the presence of a tumor. Transducer arrays which are commonly used for TTFields delivery were placed on the scalp, i.e., the placement, shape and size, current density and configuration of the transducer arrays mimicked as closely as possible a commercial device. The electric field was calculated using the finite element method. Our previous calculations predicted that the electric field magnitude exceeded 1 V/cm over large areas of the brain for the two transducer array configurations in use. Based upon in vitro experiments this value should be sufficiently high to arrest cell proliferation. Even so, a higher clinical efficacy of TTFields was expected in view of the in-vitro results. Also, a large variability in the treatment response among patients has been observed in all TTFields studies. We also observed that the electric field is not uniform as it is affected by the distribution of tissue types, the location and orientation of interfaces between them, and their individual electrical properties. Differences in the electric field distribution produced by varying the position and size of the tumor and the placement of the transducer arrays might explain some of the observed variability in response among GBM patients. By calculating the detailed electric field distribution within the realistic head model for varying tumor properties and changing transducer array setups, we hope to further advance our understanding of the mechanism(s) of action of TTFields therapy while creating a framework for personalized TTFields therapy.