Impact of Peritumoral Edema During Tumor Treatment Field Therapy: A Computational Modelling Study.

Stefan T Lang,John J P Kelly,Liu Shi Gan,Oury Monchi,Cael Mclennan

doi:10.1109/tbme.2020.2983653

Abstract

Tumor treatment fields (TTFie-lds) are an approved adjuvant therapy for glioblastoma (GBM). The magnitude of applied electrical field has been shown to be related to the anti-tumoral response. However, peritumoral edema may result in shunting of electrical current around the tumor, thereby reducing the intra-tumoral electric field. In this study, we systematically address this issue with computational simulations. Finite element models are created of a human head with varying amounts of peritumoral edema surrounding a virtual tumor. The electric field distribution was simulated using the standard TTFields electrode montage. Electric field magnitude was extracted from the tumor and related to edema thickness. Two patient specific models were created to confirm these results. The inclusion of peritumoral edema decreased the average magnitude of the electric field within the tumor. In the model considering a frontal tumor and an anterior-posterior electrode configuration, ≥6mm of peritumoral edema decreased the electric field by 52%. In the patient specific models, peritumoral edema decreased the electric field magnitude within the tumor by an average of 26%. The effect of peritumoral edema on the electric field distribution was spatially heterogenous, being most significant at the tissue interface between edema and tumor. The inclusion of peritumoral edema during TTFields modelling may have a dramatic effect on the predicted electric field magnitude within the tumor. Given the importance of electric field magnitude for the anti-tumoral effects of TTFields, the presence of edema should be considered both in future modelling studies and when planning TTField therapy.

Highlights

G LIOBLASTOMA Multiforme (GBM) is an aggressive primary brain tumor with a median survival of approximately 1 year, despite surgical and adjuvant treatment [1]
We further demonstrated the effects of peritumoral edema on electric field distribution using patient specific models with detailed tumor segmentation
In the no edema models, we modelled the peritumoral edema as normal white matter (σ = 0.126 S/m) given that the bulk of edema was located within white matter

Summary

Introduction

G LIOBLASTOMA Multiforme (GBM) is an aggressive primary brain tumor with a median survival of approximately 1 year, despite surgical and adjuvant treatment [1]. TTFields are based on the observation that low intensity, intermediate frequency (10–1000 kHz) alternating electrical fields can selectively arrest the growth of cancerous cells [2], [3]. This effect has been proposed to occur through a variety of mechanisms. During cytokinesis, a non-uniform electric field is induced which is enhanced at the furrow region separating the two dividing daughter cells. This is hypothesized to attract charged molecules from the cytosol, compromising normal cell division [2]. These antimitotic effects are related to orientation, frequency, and intensity of the applied electrical field [2], [3]

Objectives

Methods

Results

Discussion

Conclusion