Author of

• 35273

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  P25 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Mesothelioma Preclinical, Prognostic and Predictive Factors (ID 139)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35284

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    P25.10 - Computational Simulations on Safety of Tumor Treating Fields Delivered to the Lungs in Mesothelioma and NSCLC (ID 3530)

    00:00 - 00:00  |  Presenting Author(s): Ze'ev Bomzon
    • Abstract
    • Slides

    Introduction
    

    Tumor Treating Fields (TTFields) inhibit cancer cell division by utilizing low intensity alternating electric fields in the intermediate frequency. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma (MPM). The phase 2 trial STELLAR trial (Ceresoli et al, Lancet Onc 2019; NCT02397928) demonstrated promising results with a median overall survival of 18.2 months (95% CI 12.1‍–‍25.8) in patients with MPM treated with TTFields plus standard of care chemotherapy. The efficacy of TTFields therapy depends on the frequency of the electric field: 150 kHz is the optimal frequency for MPM and Non-Small-Cell lung cancer (NSCLC). Preclinical studies suggest that treatment efficacy increases with the intensity of the electric field. The higher the field intensity, the larger the therapeutic effect, with a therapeutic threshold of 0.7 V/cm above which TTFields exert a significant anti-mitotic effect. However, Delivery of an electric field to the body unavoidably leads to deposition of heat in the tissue, and it is important to insure that TTFields are delivered in an optimal manner so as not to lead to thermal damage of the patient’s tissues. Here we performed numerical simulations to determine the thermal safety of TTFields at therapeutic levels delivered to the upper torso.

    Methods
    

    Delivery of TTFields to the thorax of computational models using the Optune Lua device was simulated. Male, female, and obese models (Virtual Population, IT’IS foundation) were used. Numerical simulations were performed using Sim4life (v3.0, ZMT Zurich). The field intensities within the lungs of the models were evaluated. Thermal safety was analyzed using specific absorption rate (SAR), which is a metric for assessing heating due to electromagnetic absorption.

    Results
    

    The simulations showed that for all 3 models, the Optune Lua device delivers TTFields at therapeutic intensities greater than 0.7 V/cm RMS to cover at least 76% of the lungs. SAR values within the internal organs were generally below the levels at which thermal damage occurs (10 W/kg) as set out in the ICNIRP guidelines for occupational exposure (Health Phys 1998;74:494–522) with maximum SAR levels not exceeding 20 W/kg. In the superficial body layers higher SAR values were observed. However, the Optune Lua device incorporates temperature control that prevents the skin from heating to levels at which thermal damage can occur.

    Conclusion
    

    The results of this study support the observations that Optune Lua delivers TTFields to the lungs at therapeutic levels in a manner that is unlikely to cause thermal damage in patients. Optune Lua is safe for use in MPM and NSCLC. These data will help in ongoing and planned NSCLC clinical trials, such as the phase 3 LUNAR trial [NCT02973789] that is currently investigating the efficacy of TTFields therapy combined with immune checkpoint inhibitors or docetaxel.

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