Guidelines for Burr Hole Surgery in Combination With Tumor Treating Fields for Glioblastoma: A Computational Study on Dose Optimization and Array Layout Planning

Tumor treating fields (TTFields) is an anti-cancer technology increasingly used for the treatment of glioblastoma. Recently, cranial burr holes have been used experimentally to enhance the intensity (dose) of TTFields in the underlying tumor region. In the present study, we used computational finite element methods to systematically characterize the impact of the burr hole position and the TTFields transducer array layout on the TTFields distribution calculated in a realistic human head model. We investigated a multitude of burr hole positions and layouts to illustrate the basic principles of optimal treatment planning. The goal of the paper was to provide simple rules of thumb for physicians to use when planning the TTFields in combination with skull remodeling surgery. Our study suggests a number of key findings, namely that (1) burr holes should be placed directly above the region of interest, (2) field enhancement occurs mainly underneath the holes, (3) the ipsilateral array should directly overlap the holes and the contralateral array should be placed directly opposite, (4) arrays in a pair should be placed at far distance and not close to each other to avoid current shunting, and finally (5) rotation arrays around their central normal axis can be done without diminishing the enhancing effect of the burr holes. Minor deviations and adjustments (<3 cm) of arrays reduces the enhancement to some extent although the procedure is still effective in these settings. In conclusion, our study provides simple guiding principles for implementation of dose-enhanced TTFields in combination with burr-holes. Future studies are required to validate our findings in additional models at the patient specific level.