SCIDOT-52. IN SITU DELIVERY OF TUMOR TREATING FIELDS THERAPY IN GLIOBLASTOMA PATIENTS

Abstract The efficacy of Tumor-Treating Fields (TTFields) rests on the result of a large-scale clinical trial that demonstrated an increase in the survival of newly diagnosed glioblastoma patients when combined with temozolomide chemotherapy. Overall survival now extends to over 60 months in some of our patients when dexamethasone, which we suspected of interference with TTFields effects, is replaced with celecoxib to control tumor-associated inflammation. The transcranial method of delivering TTFields has not changed in light of ongoing advances in deep brain stimulation (DBS) and transcranial electric stimulation (TES), notably that the resistivity of the skull is the principle obstacle to placing therapeutic electric field strength of 2 V/cm into target tumor sites and variation in skull thickness is the main difference in TES efficiency across individuals. Realistic human head finite element modeling (FEM) predicted that surgical craniectomy beneath TTFields’ electrodes would enhance field strength at target tumor sites. Here we show that 2 V/cm can be reliably delivered to tumor sites using minimally-invasive DBS cylindrical leads or ribbon electrode arrays, pre- or post-resection. Two objections arise to the in situ method: 1) Will TTFields stimulate axons in situ? 2) Will field strength exceed safety limits for cell damage? Neural stimulation modeling and experiments show that TTFields’ frequency of 200 kHz, 1–3 orders of magnitude higher than ion channel time constants, is too high to stimulate them. Furthermore, 2 V/cm is well below cell damage limits of 700 V/mm. Thus we propose a new delivery method to improve tumor control in glioblastoma patients and to provide valuable information on TTFields’ effects via cell studies using in situ electric fields at 200 kHz.