Abstract 3199: Computational studies show that Tumor Treating Fields can be delivered to the infratentorial brain at therapeutic levels

Abstract

TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz), approved by the Food and Drug Administration (FDA) for the treatment of Glioblastoma Multiforme (GBM) located in the supratentorial regions of the brain. A clinical trial testing the efficacy of TTFields for treating brain metastases is currently underway (METIS, NCT02831959). TTFields are delivered using two pairs of transducer arrays placed on the patient's skin in the proximity of the tumor. The electric field generated by the arrays is localized to a region located roughly between the arrays. The standard array layouts used to deliver TTFields involve placement of the arrays on the supratentorial regions of the head. With these array layouts,therapeutic field intensities above 1 V/cm are only achieved within the supratentorial brain. Therefore, treatment with TTFields has been limited to tumors located in the supratentorium. Although Tumors located in the infratentorial brain are rare in adult patients, they are common in the pediatric population. In addition, brain metastases commonly occur in the infratentorium. Hence, there is a need to identify array layouts that can effectively deliver TTFields to the infratentorial brain. Here we present computer simulations designed to identify new array layouts that deliver high field intensities to the infratentorial brain. To simulate delivery of TTFields to the brain, we used realistic computerized head models of an adult human female and an adult human male. Virtual transducer arrays were placed on the models, and boundary conditions were set to simulate delivery of TTFields at 200 kHz. Various array layouts were tested, and field distributions resulting from the layouts were evaluated. In both head models, the highest field intensities were delivered to the infratentorial brain by a layout, in which each array of one pair was laterally placed superficially to the lower region of the occipital lobe, and the two arrays of the second pair were placed on the calvarium and the superior aspect of the neck. In both models, the pair of arrays in which one array was placed on the calvarium and one array on the superior aspect of the neck delivered field intensities above 1.1 V/cm to over 95% of the volume of the infratentorial brain, and the pair of arrays placed on the lateral aspects of the occipital lobe delivered field intensities above 1 V/cm to over 95% of the infratentorial brain. Both pairs of arrays delivered field intensities above 1 V/cm to significant portions of the supratentorial brain. This work shows that TTFields at therapeutic intensities can be delivered to the cerebellum, stem and surrounding regions which are located inferior to the tentorium, suggesting that treatment of tumors within these with TTFields is feasible. Citation Format: Shay Levy, Ariel Naveh, Ze'ev Bomzon, Eilon Kirson, Uri Weinberg. Computational studies show that Tumor Treating Fields can be delivered to the infratentorial brain at therapeutic levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3199.