Abstract 689: Heating of head tissues during TTFields therapy: A computational study
Authors: Nichal Gentilal, Ricardo Salvador, Pedro C. Miranda
Journal: Cancer Research (2019)

Abstract Tumor Treating Fields (TTFields) is a non-invasive technique that can be applied jointly with chemotherapy to treat glioblastoma (GBM). It consists on delivering an alternating current (900 mA) with a frequency of 200 kHz in two perpendicular directions alternately: Anterior-Posterior (AP) and Left-Right (LR) via capacitively coupled transducer arrays placed on the shaved scalp. This technique showed an anti-mitotic effect when the electric field magnitude in the tumor is at least 1 V/cm and the results were enhanced for values up to 3 V/cm. Optune is the FDA-approved device that was created by Novocure to deliver TTFields in humans. Due to the high daily compliance that is necessary for this technique (at least 18 hours, every day) biological tissue heating can occur. To prevent an excessive temperature increase, Optune shuts down the applied field in both directions every time an electrode reaches 41ºC. Our aim is to estimate Optune’s duty cycle, suggest ways to improve it and appraise possible thermal damage mechanisms. The simulations were performed in a realistic head model created from MR images and the software used to run these simulations was COMSOL Multiphysics. The results obtained showed that Optune is only effectively delivering the fields around 40% of the time and that the AP configuration is applied during more time than the LR. However, we show that it is possible to increase Optune’s duty cycle if 1) the current is shutdown only for the configuration that has the electrode that reached 41ºC while maintaining the other configuration active; 2) the current is injected homogeneously across all the electrodes of the same array; 3) the room temperature is low. We also calculated the Cumulative number of Equivalent Minutes at 43ºC (CEM 43ºC) for 18 hours to evaluate the possible thermal damage mechanisms. Our results showed that thermal damage might occur for the scalp and for the brain. For the scalp, these findings are corroborated with what is seen experimentally because most of the patients treated with this technique suffer from dermatitis. Regarding the brain, the impact of the temperature increase is still unclear as no related effects have been reported to date in clinical trials. However, according to the literature, an increase in temperature may lead to a higher Blood-Brain Barrier (BBB) permeability, a variation of the brain’s blood flux and a change in the concentration of some neurotransmitters such as GABA, glycine and glutamate. An increased BBB permeability can be helpful if there is a more suitable drug that can be used for GBM that under normal conditions would not pass to the brain. An increased blood flux can also be helpful to reduce brain’s temperature, while a variation in the concentration of the neurotransmitters is unlikely to affect TTFields efficacy. These results can serve as a starting point for future studies to evaluate the thermal impact of this therapy. Citation Format: Nichal Gentilal, Ricardo Salvador, Pedro C. Miranda. Heating of head tissues during TTFields therapy: A computational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 689.