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

Author:

Mikic Nikola12ORCID,Gentilal Nichal3,Cao Fang45,Lok Edwin6,Wong Eric T7,Ballo Matthew8,Glas Martin9ORCID,Miranda Pedro C3,Thielscher Axel45,Korshoej Anders R12

Affiliation:

1. Department of Neurosurgery, Aarhus University Hospital , Aarhus , Denmark

2. Department of Clinical Medicine, Aarhus University , Aarhus , Denmark

3. Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências da Universidade de Lisboa , Lisboa , Portugal

4. Department of Health Technology, Center for Magnetic Resonance, Technical University of Denmark , Kgs. Lyngby , Denmark

5. Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre , Hvidovre , Denmark

6. Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center , Boston, Massachusetts , USA

7. Division of Hematology/Oncology, Department of Medicine, Rhode Island Hospital , Providence, Rhode Island , USA

8. Department of Radiation Oncology, West Cancer Center and Research Institute , Memphis, Tennessee , USA

9. Division of Clinical Neurooncology, Department of Neurology and German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, University Duisburg-Essen , Essen , Germany

Abstract

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 of TTFields 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 the TTFields distribution and dose measurement in the brain and highlights the most important principles governing TTFields 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 between TTFields dose, tumor growth, and clinical outcome will be presented and discussed. Furthermore, we will provide perspectives and updated insights into the planning and optimization of TTFields therapy for glioblastoma by reviewing how the dose and thermal effects of TTFields 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.

Publisher

Oxford University Press (OUP)

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