Thermal safety and effectiveness of tumor treating fields’ delivery to the abdomen as determined by computational simulations.

Abstract

272 Background: Tumor Treating Fields (TTFields), an antimitotic cancer treatment, utilizes low intensity (1-3 V/cm), intermediate frequency (100-300 kHz), alternating electric fields delivered non-invasively by transducer arrays placed on skin over tumor region. Safety of TTFields has been established in pancreatic cancer (Phase II study; PANOVA; NCT01971281). A Phase 3 study in locally-advanced pancreatic cancer (PANOVA-3) and a phase 2 study in hepatocellular cancer are ongoing. Preclinical studies suggest that TTFields’ intensity correlates with treatment efficacy. Simulations can determine the thermal safety of TTFields by evaluating tissue heating due to field absorption and resultant risk of thermal damage. We used computational simulations to study the effectiveness of field distribution and associated heating in realistic phantoms during TTFields delivery to the abdomen. Methods: Delivery of TTFields to computational phantoms of a male (DUKE 3.0), a female (ELLA 3.0) and an obese male (FATS 3.0) was simulated. For each phantom, 6-8 different transducer array layouts to the abdomen were tested. Specific Absorption Rate (SAR) levels were calculated to assess the risk of thermal damage to tissues, and compared to the SAR control level of 10 W/kg per International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for occupational exposure (Health Physics 74 (4) 494; 1998). The field intensities were measured to determine the effectiveness of treatment delivery. Results: Altering the size and position of the arrays facilitates field intensities above the therapeutic threshold of 1 V/cm. Within the abdominal internal organs, the SAR values were generally below the ICNIRP recommended level of 10 W/kg. The maximum SAR levels did not exceed 20 W/kg. Conclusions: TTFields could be delivered at intensities above therapeutic threshold of 1 V/cm by strategizing the array size and placement. TTFields to the abdomen can be delivered to target gastrointestinal cancers without causing thermal damage to abdominal tissues. These results also indicate that TTFields delivery can be optimized in gastrointestinal cancers.