Abstract 688: Safety and efficacy of TTFields delivery to the lungs: A computational study

• Published in: Cancer research (Chicago, Ill.) Ill.), 2019-07, Vol.79 (13_Supplement), p.688-688
• Main Authors: Hershkovich, Hadas Sara, Urman, Noa, Naveh, Ariel, Bomzon, Zeev
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2019-688

Objective: This study investigates the efficacy and safety of Tumor Treating Fields (TTFields) delivery to the lungs utilizing computational simulations. Introduction: Recent results of a phase 2 clinical trial STELLAR (NCT02397928) demonstrated a significant extension in median overall survival among patients with mesothelioma treated with TTFields plus standard of care chemotherapy compared to historical control data of patients who received standard of care chemotherapy alone. A phase 3 clinical trial (NCT02973789) is currently investigating the efficacy of TTFields therapy for the treatment of Non-Small-Cell lung cancer (NSCLC). The efficacy of TTFields therapy in disrupting tumor cells depends on the frequency of the field (150kHz optimal frequency for NSCLC and mesothelioma) and the field intensity. The higher the field intensity, the larger the therapeutic effect, with a therapeutic threshold of 0.7 V/cm above which TTFields begin to exert a significant anti-mitotic effect on cells. Delivery of an electric field to the body unavoidably leads to deposition of heat in the tissue through Joule heating. The rate at which electrical energy is absorbed and converted to heat, depends on field’s frequency and tissue’s properties. Since Joule heating may cause thermal damage, it is important to ensure that TTFields intensity in the body is below the thermal damage threshold. In this study we performed numerical simulations to evaluate the thermal safety and the efficacy of the NovoTTF-100L when delivering Tumor Treating Fields to the torso. Thermal safety threshold levels were determined by current density and specific absorption rate (SAR) and TTFields therapeutic threshold was determined by field intensity. Methods: We investigated field intensity, current density and SAR values that developed within 3 different realistic human computational models in which a virtual representation of the NovoTTF-100L (150kHz) was used to deliver TTFields to the lungs. The models used in this study include: a female model, male model and an obese male model (Virtual Population, IT’IS foundation) with a range of BMI values from normal to obese. Numerical simulations were performed using Sim4life (v3.0, ZMT Zurich). Results: The simulations show that for all models, the NovoTTF-100L delivers therapeutic intensities of over 0.7 V/cm RMS to over at least 76% of the lungs. Current density within the models is well below the safety threshold of 100 mA/cm^2. SAR values within the