Abstract 2051: Tumor-treating fields (TTFields) intensity in the gross tumor volume and peritumoral brain zone: implications for local recurrence in glioblastoma
Authors: Chaudhry Aafia , Bomzon Zeev , Hershkovich Hadas Sara , Garcia-Carracedo Dario , Wenger Cornelia , Weinberg Uri , Palti Yoram 
Published: July 2016

Abstract
The purpose of this study was to simulate the intensity of TTFields delivered to the brain during the course of glioblastoma (GBM) treatment and to determine whether therapeutic intensities are delivered to the proximal peri-tumoral brain zone (PBZ). Background: TTFields are low-intensity (1-3 V/cm), intermediate frequency (200kHz), alternating electric fields delivered orthogonally in a localized manner during the course of GBM therapy. A recent phase 3 randomized, controlled trial conducted in patients newly diagnosed with GBM was stopped early for efficacy when the end points for progression-free survival (PFS) and overall survival (OS) were met at the interim analysis. Patients receiving TTFields in combination with temozolomide (TMZ) had a significantly longer PFS and OS compared with patients receiving TMZ alone. More than 90% of GBM recur at the margin of a resection cavity or within the PBZ where the presence of infiltrating tumor cells, inflammatory cells and tumorigenic stromal cells are thought to promote recurrence. Phantom model simulation studies suggest that field intensities &gt;1V/cm are delivered to the brain in a non-uniform distribution, however the field distribution to the gross tumor volume (GTV) and PBZ have not been previously evaluated. Methods: Two MRI cases (frontal and posterior-parietal tumors) were used to generate TTFields treatment array layout maps using NovoTAL(TM) System planning software, targeting areas of contrast enhancement on T1 sequences. Simulations for the respective array layouts were created for solid tumors, resection cavities and for tumors with a necrotic core (modified Colin27 model, meshed and solved using the Sim4Life software solver package). Two orthogonal fields (left-right and antero-posterior) at a field frequency of 200 kHz were employed for all simulations. Field intensity was determined in the GTV, tumor margin(TM) and proximal PBZ (20mm) for all models. Results: Transducer array layout maps generated by the NovoTAL software deliver therapeutic intensities of TTFields in both L-R and A-P directions. Bi-directional intensities exceed therapeutic levels (&gt;1 V/cm) in the GTV (median 1.84 V/cm), TM (median 1.9 V/cm) and PBZ (median 2.09 V/cm) in all solid tumors and in the PBZ (median 1.83 V/cm) surrounding a gross total resection (GTR) cavity. The highest areas of field intensity are observed directly adjacent to resection cavities and the ventricles. Conclusions: The delivery of therapeutic intensities of TTFields to patients who have undergone a GTR, subtotal resection or who have inoperable GBM, targets therapy to the area of active disease and importantly, to the PBZ. TTFields target residual tumor cells in the GTV and may also disrupt infiltrating tumor cells in the PBZ. Clinically, this may decrease local GBM recurrence rates and prospective clinical studies are warranted to explore this further.
Citation Format: Aafia Chaudhry, Zeev Bomzon, Hadas Sara Hershkovich, Dario Garcia-Carracedo, Cornelia Wenger, Uri Weinberg, Yoram Palti. Tumor-treating fields (TTFields) intensity in the gross tumor volume and peritumoral brain zone: implications for local recurrence in glioblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2051.