Tumor-treating fields dosimetry in glioblastoma: Insights into treatment planning, optimization, and dose–response relationships

Abstract

Tumor-treating fields (TTFields) are currently a Category 1A treatment recommendation by the US National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action ofTTFields has been partly elucidated, tangible and standardized metrics are lacking to assess antitumor dose and effects of the treatment.This paper outlines and evaluates the current standards and methodologies in the estimation of theTTFields distribution and dose measurement in the brain and highlights the most important principles governingTTFields dosimetry.The focus is on clinical utility to facilitate a practical understanding of these principles and how they can be used to guide treatment.The current evidence for a correlation betweenTTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization ofTTFields therapy for glioblastoma by reviewing how the dose and thermal effects ofTTFields are affected by factors such as tumor location and morphology, peritumoral edema, electrode array position, treatment duration (compliance), array “edge effect,” electrical duty cycle, and skull-remodeling surgery. Finally, perspectives are provided on how to optimize the efficacy of future TTFields therapy.