Abstract
Tumor-treating fields have potential as minimally invasive cancer treatment. This study aimed to explore the optimum tumor-treating field conditions that minimize unpredicted variations in therapeutic outcomes resulting from differences in cell size and electrical properties. The electric field concentration that induces a dielectrophoretic force near the division plane of a mitotic cell was calculated by finite element analysis for 144 cases, based on different combinations of six noise factors associated with cells and four controllable factors including frequency, as determined by the Taguchi method. Changing the frequency from 200 to 400 kHz strongly increased robustness in producing a dielectrophoretic force, irrespective of noise factors. However, this frequency change reduced the force magnitude, which can be increased by simply applying a higher voltage. Based on additional simulations that considered this trade-off effect, a frequency of 300 kHz is recommended for a robust TTF treatment with allowable variations. The dielectrophoretic force was almost independent of the angle of applied electric field deviated from the most effective direction by ±20 degrees. Furthermore, increased robustness was observed for extracellular fluid with higher conductivity and permittivity. The Taguchi method was useful for identifying robust tumor-treating field therapy conditions from a considerably small number of replicated simulations.
Highlights
A tumor-treating field (TTF) is a weak AC electric field of several hundred kHz to 1 MHz that interferes with cell division
The optimum condition of TTF treatment with a high robustness to unpredictable variations in cell size and electrical properties was investigated by numerical simulations in which an AC voltage was applied to a mitotic cell
The magnitude of the dielectrophoretic force near the plane of cell division was evaluated for different voltages for combinations of six uncontrollable noise factors and four controllable factors
Summary
A tumor-treating field (TTF) is a weak AC electric field of several hundred kHz to 1 MHz that interferes with cell division. Despite the low intensity of these electric fields, at only a few volts per centimeter, both cell and animal experiments have confirmed that TTFs can arrest tumor cell proliferation and promote cell destruction [1], which renders TTF as a minimally invasive cancer treatment. A pilot clinical trial targeting recurrent glioblastoma (GBM) demonstrated that an AC electric field of 1–2 V/cm at a frequency of 100–200 kHz nearly doubled both the time to disease progression and overall survival (OS) among those reported far [2]. A phase III randomized clinical trial for recurrent GBM, which was conducted following these promising preclinical studies, has demonstrated that TTF treatment results are comparable to those for chemotherapy [3].
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