Computational Simulations to Determine Optimal Array Layouts for Delivering TTFields to the Lungs

Abstract

Tumor treating fields (TTFields) are low intensity, alternating electric fields in the intermediate frequency range. TTFields disrupt mitosis, and are FDA approved for the treatment glioblastoma (GB). Preclinical models suggest that TTFields could be effective in the treatment of non-small-cell lung cancer (NSCLC) and mesothelioma. Their safety when combined with pemetrexed was established in a pilot clinical trial of NSCLC patients. A study to test the efficacy of TTFields in combination of chemotherapy for the treatment of mesothelioma is underway, and a pivotal study testing the efficacy of TTFields in treating NSCLC is planned. TTFields are delivered through 2 pairs of transducer arrays (TL) placed on the patient's skin. Preclinical studies suggest that treatment efficacy increases when the intensity of the electric field increases. Therefore personalizing the array placement to deliver optimal field distributions is important. In-fact, array layout personalization to optimize the field intensity is a prerequisite when treating GB patients. However, optimal array layouts for lung cancer patients have yet to be determined. Here we present a computational simulations-based study investigating optimal array layouts in male and female anatomic models. Simulations were performed using the Sim4Life software package and the DUKE and ELLA computational models (ZMT, Zurich, Switzerland).The models were linearly scaled to represent individuals with different dimensions, and the distribution of TTFields within the thorax of these models was calculated for a variety of array layouts. The layouts were then ranked. Layouts that conformed well to body contours and delivered uniform high intensity fields to the lungs received the highest rankings. Optimal distribution of the fields within the lungs is obtained when the arrays are axially-aligned with the parenchyma as much as anatomically possible. For male subjects, the highest ranking layouts were those in which one pair of arrays delivered an electric field from the anterolateral to the posterior-contralateral aspect of the patient, with the second pair delivering the field from the antero-contralateral to the posterolateral aspect of the patient. Similar cross-body array layouts ranked high for females, too. However, due to body contours, cross-layouts do not adhere well to smaller females, potentially hampering the efficient delivery of TTFields. For these patients, a layout in which 1 pair of arrays is placed on the lateral and contralateral aspects of the patients, and the second set of arrays is placed on the anterior and posterior aspects of the patient are preferred. This study provides insights into how TL layout influences TTFields distribution in the lungs. The results should be accounted for when developing guidelines for TL placement when treating lung cancer.