Transducer array layout optimization for the treatment of pancreatic cancer using Tumor Treating Fields (TTFields) in the phase 3 PANOVA-3 trial.

person Ariel Naveh Novocure Ltd., Haifa, Israel info_outline Ariel Naveh, Hadas Sara Hershkovich, Eilon David Kirson, Uri Weinberg, Zeev Bomzon

Authors person Ariel Naveh Novocure Ltd., Haifa, Israel info_outline Ariel Naveh, Hadas Sara Hershkovich, Eilon David Kirson, Uri Weinberg, Zeev Bomzon Organizations Novocure Ltd., Haifa, Israel, Novocure, Haifa, Israel Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz), which are delivered in two orthogonal directions using 2 pairs of transducer arrays. Based on favorable results in a Phase 2 study in locally-advanced pancreatic cancer (LAPC), an ongoing Phase 3 PANOVA-3 trial [NCT03377491] is investigating the efficacy of adding TTFields to nab-paclitaxel and gemcitabine in LAPC. 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. The current study was designed to develop clinical practice guidelines for optimizing the layout of arrays applied to patients participating in the TTFields arm of the PANOVA-3 study. Methods: Three realistic computerized models of a male, a female and an obese male were used to simulate delivery of TTFields to the abdomen. 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 regions, and field intensity distributions within these regions were evaluated. Results: In all simulations, the large arrays generated higher field intensities than the smaller arrays. However, models with lower BMI were almost covered entirely using large arrays, increasing the potential of skin toxicity from TTFields. However, these Low BMI models were able to receive TTFields at an anti-mitotic intensity with smaller arrays. The clinical guidelines were formulated based on the following principles: the target tumor region should be directly between the arrays, (b) the extent of disease as well as the anatomy of the patient determines the size of arrays determined using waist circumference measurements. Conclusions: A matrix for selecting between 8 individual array layouts was generated based on these principles. The clinical practice guidelines allow the optimization of TTFields delivery to individual patients treated in the PANOVA-3 Study.