Non-Invasive Radiofrequency Field Treatment to Produce Hepatic Hyperthermia: Efficacy and Safety in Swine

Abstract

The Kanzius non-invasive radio-frequency hyperthermia system (KNiRFH) has been investigated as a treatment option for hepatic hyperthermia cancer therapy. The treatment involves exposing the patient to an external high-power RF (13.56 MHz) electric field, whereby the propagating waves penetrate deep into the tumor causing targeted heating based on differential tissue dielectric properties. However, a comprehensive examination of the Kanzius system alongside any associated toxicities and its ability to induce hepatic hyperthermia in larger animal models, such as swine, are the subjects of the work herein. Ten Yucatan female mini-swine were treated with the KNiRFH system. Two of the pigs were treated a total of 17 times over a five-week period to evaluate short- and long-term KNiRFH-associated toxicities. The remaining eight pigs were subjected to single exposure sessions to evaluate heating efficacy in liver tissue. Our goal was to achieve a liver target temperature of 43°C and to evaluate toxicities and burns post-treatment. Potential toxicities were evaluated by contrast-enhanced MRI of the upper abdomen and blood work, including complete metabolic panel, complete blood count, and liver enzymes. The permittivities of subcutaneous fat and liver were also measured, which were used to calculate tissue specific absorption rates (SAR). Our results indicate negligible KNiRFH-associated toxicities; however, due to fat overheating, liver tissue temperature did not exceed 38.5°C. This experimental limitation was corroborated by tissue permittivity and SAR calculations of subcutaneous fat and liver. Significant steps must be taken to either reduce subcutaneous fat heating or increase localized heating, potentially through the use of KNiRFH-active nanomaterials, such as gold nanoparticles or single-walled carbon nanotubes, which have previously shown promising results in murine cancer models.

Improved, Shorter-Latency Carcinogen-Induced Hepatocellular Carcinoma Model in Pigs

“…7a, b) yielded a calculated relative heating rate of liver, tumor, and fat as shown in Figure 8 (utilizing tissue mass density of ρ liver = ρ tumor = 1.06 g/mL and ρ fat = 0.9 g/mL) by electromagnetic energy in the radiofrequency-microwave spectrum. The relative heating rate was calculated using the simplified infinite tissue layer approximation as previously described [33]. Using this model, the difference in calculated heating rate between liver and tumor tissues did not exceed 3.5% for the measured frequency spectrum from 10 to 1,000 MHz, whereas the heating rate of fat was approximately 5-6 times greater than that of liver and tumor tissues, similar to our previous study [33].…”

“…Hyperthermia is thought to potentiate both chemo-and radiation therapy in the treatment of malignancies [36,37]. Using the simplified approximation of infinite tissue planes, we have previously shown that subcutaneous fat heats at a rate 5.8-to 7.3-fold greater than liver tissue at an exposure frequency of 10-3,000 MHz [33]. In the current study, the heating rates were calculated for liver, tumor, and fat tissues for the frequency range of 10-1,000 MHz as previously described.…”

Heating technology for malignant tumors: a review

“…Therefore, excessive temperatures (hot spots) can occur at tissue interfaces, and due to the orientation of the main electric field component, which is perpendicular to fat layers, especially excessive heating of fat tissue can be treatment limiting when using this technique [27][28][29]. Therefore, capacitive heating becomes less effective with increasing thickness of the fat layer and heating of deep-seated tumors can be challenging [30][31][32].…”

Proposal and Challenge of Halbach Array Type Induction Coil for Cooktop Applications

“…In industrial use, aluminum melting technique using induction heating is typical, contributing to energy saving and safety improvement of factory equipment [2]- [4]. As a typical example of medical applications, induction heating technology is used in thermotherapy equipment for cancer (hyperthermia) [5]- [6]. For home appliances, it is widely used in cooktops [7]- [10].…”