Standardizing Skullremodeling Surgery and Electrode Array Layout to Improve Tumor Treating Fields Using Computational Head Modeling and Finite Element Methods

Abstract

AbstractSkullremodeling surgery (SR-surgery) includes removing bone from the skull to enhance TTFields. In our phase 1 trial (NCT02893137) we tested multiple SR-configurations (craniectomy, burrholes, and skull thinning) with TTFields concluding it to be safe. To examine the efficacy, we recently initiated an investigator-initiated, randomized, comparative, multi-center phase 2 trial (NCT04223999).To ensure uniformity, SR-surgery will be standardized to 5 burrholes of 15 mm diameter placed cross-diagonally in a 45×45 mm square above the tumor. The configuration was chosen as a combination of maximizing the overall cm3 while not compromising patient safety.To create a standard operating procedure for the trial, we wanted to examine how the electric field was affected by this SR-surgery configuration, its location, and the electrode array placement. We created E-field simulations based on a computational head model, that mimicked a trial patient’s tumor resection cavity, residual tumor, and SR-surgery. SR-surgery was virtually applied at several locations with different electrode positions to investigate the impact on the electric field in the residual tumor tissue, resection cavity, and grey- and white matter. The electrode arrays were moved by 15-degree stepwise rotation around a central craniocaudal axis in the same horizontal plane, corresponding to 0–180 degrees for a total of 13 different positions. Control simulations without SR-surgery were also performed.In general, we found that SR-surgery increased the electric field strength significantly in the residual tumor and resection cavity with minimal effect on the healthy white and grey matter tissue. The highest electric field values were observed in the residual tumor and resection cavity when the burrholes were placed directly above the pathological tissue and the edge electrodes of both pairs were placed on top or close to the burrholes with the reference electrode directly opposite on the head.