The study of the dielectric properties of tissues plays a key role in understanding the interaction between electromagnetic energy and the human body, for safety assessments of human exposure to electromagnetic fields, as well as for numerous biomedical applications such as tumor treating fields (TTFields). TTFields are low-intensity alternating electric fields in the 100–500 kHz frequency range, which have an antimitotic effect on cancerous cells. TTFields are delivered to the body through pairs of transducer arrays placed on a patient’s skin in close proximity to the tumor. Therefore, it is essential to understand how the skin’s dielectric properties affect TTFields delivery in clinical settings. In this paper, we present a study combining in vivo measurements with numerical simulations that elucidate how different layers of the skin influence TTFields distribution in the body. The dielectric properties of the skin were measured on volunteers using a setup that ensured skin conditions resembled those when TTFields are delivered to patients. The measured properties were incorporated into a realistic human computational phantom and delivery of TTFields to the phantom’s abdomen was simulated. The total impedance of the simulated model was within the mid-range of impedance values measured in patients with pancreatic cancer treated with TTFields. A computational study investigating model sensitivity to the dielectric properties of the skin and subcutaneous adipose tissue (SAT) showed that when skin conductivity increased above a threshold value, the total impedance of the model was largely insensitive to changes in the conductivity of these tissues. Furthermore, for a given current, the field intensity within the internal organs was mostly unaffected by skin properties but was highly sensitive to the conductivity of the organ itself. This study provides a new insight into the role of skin in determining the distribution of TTFields within the body.

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Background and Purpose Tumor treating fields (TTFields) are a non-invasive, efficacious treatment modality currently approved for supratentorial glioblastomas. Despite their ability to improve overall survival in supratentorial tumors, the current placement of arrays is limited to the supratentorial head, precluding its use in infratentorial tumors. Infratentorial malignancies are in need of new therapy modalities given their poor prognoses in both children and adults. The aim of this research is to determine whether rearrangement of TTFields may allow for management of infratentorial tumors. Materials and methods Delivery of TTFields using Novocure’s prototype Optune™ device human male head model was simulated based on brain MRIs from patients with brainstem gliomas to develop a novel array layout designed to extend adequate infratentorial coverage. Results Array placement on the vertex, bilateral posterolateral occiput, and superior-posterior neck achieved intensities above 1.1 V/cm (average 1.7 V/cm; maximum 2.3 V/cm) in the vertical field direction and above 1 V/cm (average 2 V/cm; maximum 2.8 V/cm) in the horizontal field direction of the infratentorium. The calculated field intensity within the simulated tumors were in the therapeutic range and demonstrated the effective delivery of TTFields to the infratentorial brain. Conclusions Our findings suggest that rearrangement of the TTFields standard array with placement of electrodes on the vertex, bilateral posterolateral occiput, and superior-posterior neck allows for adequate electric field distribution in the infratentorium that is within the therapeutic range.

Introduction: TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz) that are delivered in two orthogonal directions using 2 pairs of transducer arrays. A phase II clinical trial (PANOVA, NCT01971281) showed that TTFields in combination with chemotherapy was safe in patients with locally advanced pancreatic cancer. Preclinical studies show that the effect of TTFields is intensity-dependent with a therapeutic threshold of 1 V/cm. The field distribution within the body is known to changes with array placement. Therefore, there is a need to develop principles for personalizing array placement to optimize TTFields delivery when treating pancreatic cancer. The aim of such guidelines should be to ensure delivery of maximal field intensities to the region of disease, whilst minimizing the size of the arrays placed on the body. Minimizing array size is important to enable periodic shifting of the arrays for potentially reducing skin irritation associated with TTFields therapy, as well as potentially improving overall patient comfort. Here we present a systematic study investigating how the location and size of the arrays on the abdomen influences the field distribution. Methods: To simulate delivery of TTFields to the abdomen, we used 3 realistic computerized models (from ZMT_Zurich) of: a male (DUKE 3.0); b) , a female (ELLA 3.0); and an obese male (FATS 3.0). For each model, 6-8 different layouts utilizing combinations of arrays with either 13 or 20 disks per-array were tested. The arrays were placed over the upper 6 standard abdominopelvic, and field intensity distributions within these regions were evaluated. In order to generate TTFields, an alternating voltage at a frequency of 150 KHz was imposed on the outer surfaces of the disks of each pair of arrays. The voltage was set to deliver a current of 200 mA peak to peak per-disk (total current 2.6 A for 13-disk arrays, 4.0 A for 20-disk arrays). The simulations were performed using ZMT's Sim4Life V3.0 electro-quasi-static solver. Results: In all simulations, the large arrays generated higher field intensities than the small arrays. However, On ELLA and DUKE, the large arrays covered most of the skin around the abdomen, leaving little to no room for shifting the arrays. FATs body surface is large enough so that even when large arrays are used, there is still ample space for shifting the arrays. On DUKE and ELLA, when using small arrays, the average field intensity in the abdominopelvic region over which the arrays were placed was above the therapeutic threshold of 1 V/cm. Conclusion: This work shows that TTFields array placement can be optimized to deliver therapeutic field intensities to specific abdominopelvic regions. Tailoring the size and position of the arrays based on disease site and patient size may help to improve overall treatment outcome. Citation Format: Ariel Naveh, Ze'ev Bomzon, Ori Farber, Noa Urman, Ofir Yesharim, Eilon Kirson, Uri Weinberg. Transducer array configuration optimization for treatment of pancreatic cancer using Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3204.

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