Abstract
Tumor-treating fields (TTFields) are the fourth modality of glioblastoma (GBM) treatment and in conjunction with chemotherapy can increase overall survival of GBM patients up to 60 months. However, in vitro and in animal models TTFields show 100% efficacy on a variety of tumor cell types including GBM cells when field strength is 4 V/cm, versus ~2 V/cm that is the clinical delivery target, TTFields are delivered transcranially. TTFields finite element modeling studies, supported by similar transcranial electric stimulation studies, show that the principal obstacle to delivering 4 V/cm is the electrically resistive skull. Our modeling shows the biophysics is more complicated than these findings. For instance, electrically-conductive cerebrospinal fluid regions surrounding the grey matter and in ventricles shunt electric current from anode to cathode, hindering delivery of the current required to produce 4 V/cm at the tumor/peritumor target. Thus, we consider two new delivery methods for TTFields. First, the transcranial array can be made more focal and directional, following modeling and development of electrode arrays used in spinal cord and deep brain stimulation. Our finite element modeling shows that similarly-designed TTFields electrode arrays can deliver field strength focally to a tumor target approaching 4 V/cm. Second, pre- or post-resection, TTFields can be delivered via electrode arrays surgically placed in the tumor or tumor resection cavity (intra-tumoral delivery), circumventing the resistive skull and CSF shunting effects. Such intra-tumoral arrays can deliver 4 V/cm to the tumor/peritumor region, opening up the potential to replicate clinically the 100% efficacy of TTFields in vitro and in animal models. Thus, new TTFields delivery may lead to unlimited survival of GMB patients via a side-effect free treatment modality.
A comparison of thin-plate spline deformation and finite element modeling to compensate for brain shift during tumor resection
