Simulating the Effect of 200 kHz AC Electric Fields on Tumour Cell Structures to Uncover the Mechanism of a Cancer Therapy

Carlson, Kristen W.; Tuszyński, Jack A.; Dokos, Socrates; Paudel, Nirmal; Bomzon, Zéev

doi:10.1007/978-3-030-21293-3_6

Cited by 1 publication

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References 17 publications

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“…The first hypotheses suggested a two-stage action: during metaphase, these fields could disrupt mitotic spindle formation by acting on cells' highly polar structures, and during cytokinesis, they could affect correct cell division by leading to membrane blebbing [1,2]. However, more recent studies presented some calculations that indicate that these hypotheses might not fully explain how TTFields affect the mitotic process [3], and new possible mechanisms have been suggested since [4,5]. An example of the latter are the calculations done by Berkelmann et al [5] that propose that the high energy deposited at the cleavage furrow might kill tumoral cells by overheating them during telophase and cytokinesis.…”

Section: Tumor-treating Fieldsmentioning

confidence: 99%

A Thermal Study of Tumor-Treating Fields for Glioblastoma Therapy

Gentilal

Salvador²,

Miranda

2020

Brain and Human Body Modeling 2020

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Tumor-treating fields (TTFields) is an antimitotic cancer treatment technique used for glioblastoma multiforme (GBM) and malignant pleural mesothelioma. Although the frequency used is not as high as in hyperthermia, temperature increases due to the Joule effect might be meaningful given the necessary time that these fields should be applied for. Post hoc analysis of the EF-11 clinical trial showed higher median overall survival in patients whose compliance was at least 18 h per day. To quantify these temperature increases and predict the thermal impact of TTFields delivery to the head, we used a realistic model created from MR images segmented in five tissues: scalp, skull, CSF, gray matter (GM), and white matter (WM). Through COMSOL Multiphysics, we solved Laplace’s equation for the electric field and Pennes’ equation for the temperature distribution. To mimic the therapy as realistically as possible, we also considered complete current shutdown whenever any transducer reached 41 °C to allow transducers and tissues’ temperature to decrease. Our results indicate an intermittent operation of Optune due to this necessary current shutdown. Localized temperature increases were seen, especially underneath the regions where the transducers were placed. Maximum temperature values were around 41.5 °C on the scalp and 38 °C on the brain. According to the literature, significant thermal impact is only predicted for the brain where the rise in temperature may lead to an increased BBB permeability and variation in the blood flow and neurotransmitter concentration. Additionally, our results showed that if the injected current is reduced by around 25% compared to Optune’s standard way of operating, then uninterrupted treatment might be attainable. These predictions might be used to improve TTFields delivery in real patients and to increase awareness regarding possible thermal effects not yet reported elsewhere.

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