A Review on Tumor-Treating Fields (TTFields): Clinical Implications Inferred From Computational Modeling

Abstract

Tumor-treating fields (TTFields) are a cancer treatment modality that uses alternating electric fields of intermediate frequency (∼100-500 kHz) and low intensity (1-3 V/cm) to disrupt cell division. TTFields are delivered by transducer arrays placed on the skin close to the tumor and act regionally and noninvasively to inhibit tumor growth. TTFields therapy is U.S. Food and Drug Administration approved for the treatment of glioblastoma multiforme, the most common and aggressive primary human brain cancer. Clinical trials testing the safety and efficacy of TTFields for other solid tumor types are underway. The objective of this paper is to review computational approaches used to characterize TTFields. The review covers studies of the macroscopic spatial distribution of TTFields generated in the human head, and of the microscopic field distribution in tumor cells. In addition, preclinical and clinical findings related to TTFields and principles of its operation are summarized. Particular emphasis is put on outlining the potential clinical value inferred from computational modeling.

Effect of electrical stimulation on biological cells by capacitive coupling – an efficient numerical study considering model uncertainties

“…Still, the presented model is very abstract and does not apply in every case as it neglects the interaction between different cells. Nevertheless, similar models are commonly used across different communities [17], [23], [24], [51]. More sophisticated models including many cells require large highperformance-computing facilities [52].…”

“…In that we will transfer knowledge from our previous UQ study on a human brain model [55] to the field of in vitro electrical stimulation and promote this UQ approach enabling other researchers to reuse our solution that is based on the open-source tool Uncertainpy. A possible application could be in the TTField community, where similar cell models are used [51]. Following the research presented in [29]- [31], we will realize an opensource solution for the FEM model.…”

Estimation of TTFields Intensity and Anisotropy with Singular Value Decomposition: A New and Comprehensive Method for Dosimetry of TTFields

“…A number of different approaches have been used to create computational head models for TTFields [7]. We created a patient-specific head model based on T1-and T2-weighted MRI sequences from a male patient with GBM in the left parietal region.…”

“…TTFields are induced by two electrical sources, each connected to its own pair of 3×3 transducer arrays, which are placed on the patient's body surface in the vicinity of the tumor [4]. Recently, finite element (FE) methods have been used to calculate the distribution of TTFields in realistic human head models in efforts to estimate the treatment dose of TTFields [5][6][7][8]. This has provided important information about how the TTFields distribution is affected by human head morphology [9], tumor position [10,11], tissue dielectric properties [9,10,12,13], and transducer array layout [11,14].…”

Water-Content Electrical Property Tomography (wEPT) for Mapping Brain Tissue Conductivity in the 200–1000 kHz Range: Results of an Animal Study

“…Thus, a patient-specific EP map of the brain would be optimal to accurately evaluate the induced electric field distribution and intensities at the tumor bed. For a detailed review on preclinical, clinical, and modeling studies related to TTFields, see [33].…”