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Review
. 2025 Feb 6;30(2):oyae227.
doi: 10.1093/oncolo/oyae227.

Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma

Simon Khagi  1 , Rupesh Kotecha  2 , Na Tosha N Gatson  3   4   5 , Suriya Jeyapalan  6 , Huda Ismail Abdullah  7 , Nicholas G Avgeropoulos  7 , Eleni T Batzianouli  8 , Moshe Giladi  9 , Leonardo Lustgarten  7 , Samuel A Goldlust  10
Affiliations
Review

Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma

Simon Khagi et al. Oncologist. .

Abstract

Tumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin. Based on efficacy and safety data from global pivotal (randomized phase III) clinical studies, TTFields therapy (Optune Gio) is US Food and Drug Administration-approved for newly diagnosed (nd) and recurrent glioblastoma (GBM) and Conformité Européenne-marked for grade 4 glioma. Here we review data on the multimodal TTFields mechanism of action that includes disruption of cancer cell mitosis, inhibition of DNA replication and damage response, interference with cell motility, and enhancement of systemic antitumor immunity (adaptive immunity). We describe new data showing that TTFields therapy has efficacy in a broad range of patients, with a tolerable safety profile extending to high-risk subpopulations. New analyses of clinical study data also confirmed that overall and progression-free survival positively correlated with increased usage of the device and dose of TTFields at the tumor site. Additionally, pilot/early phase clinical studies evaluating TTFields therapy in ndGBM concomitant with immunotherapy as well as radiotherapy have shown promise, and new pivotal studies will explore TTFields therapy in these settings. Finally, we review recent and ongoing studies in patients in pediatric care, other central nervous system tumors and brain metastases, as well as other advanced-stage solid tumors (ie, lung, ovarian, pancreatic, gastric, and hepatic cancers), that highlight the broad potential of TTFields therapy as an adjuvant treatment in oncology.

Keywords: Tumor Treating Fields; alternating electric field; antitumor immunity; brain tumor; glioblastoma; medical device.

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Conflict of interest statement

S.K. reports consulting/advisory relationship with Pacific Marine Biotech, Autem Therapeutics; honoraria with Novocure; ownership interests with SKBio Advisory, LLC. R.K. reports honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., Brainlab, Kazia Therapeutics, Castle Biosciences, and Ion Beam Applications; research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay Inc., Brainlab, Cantex Pharmaceuticals, Kazia Therapeutics, and Ion Beam Applications. N.N.G. reports consulting/advisory relationship with GT Medical Technologies, Guidepoint; President, Living Oncology (nonprofit). S.J. reports consulting/advisory relationship with Novocure. H.I.A. is a former employee of Novocure. N.G.A., E.T.B., M.G., and L.L. are employees of and hold stocks/shares in Novocure. S.A.G. reports consulting/advisory relationship with Cellevolve, Sumitomo Dainippon Pharma Oncology, Cornerstone Specialty Network, Daiichi Sankyo, Novocure, and Sumitomo Dainippon Pharma Oncology; travel support from Cornerstone Specialty Network, Cortice Biosciences, and Novocure; ownership interests with COTA.

Figures

Figure 1.
Figure 1.
The second-generation Tumor Treating Fields therapy medical device system. The NovoTTF-200A (Optune Gio) system consists of a portable field-generating device (with a bag), arrays, batteries, battery charger, and plug-in power supply. This system is smaller and lighter than the originally introduced NovoTTF-100A device (1.2 vs 2.7 kg). Reused with permission from 2024 Novocure GmbH—all rights reserved.
Figure 2.
Figure 2.
The anticancer effects of TTFields originate from a multimodal mechanism of action. TTFields multimodal mechanism of action impairs mitosis, the DNA damage response, and cell motility, and enhances antitumor immunity and cell and BBB permeability. Reused with permission from 2024 Novocure GmbH—all rights reserved. Abbreviations: ATP, adenosine triphosphate; BBB, blood–brain barrier; BRCA, breast cancer protein 1 or 2; DNA, deoxyribonucleic acid; ER, endoplasmic reticulum; FANC, Fanconi anemia complementation group; GBM, glioblastoma; HGG, high-grade glioma; HMGB1, high mobility group box 1 protein; PECAM-1, platelet endothelial cell adhesion molecule 1; Rho, Ras-homologous protein family; ROCK, Rho-associated protein kinase; TTFields, Tumor Treating Fields.
Figure 3.
Figure 3.
Summary of safety findings in Tumor Treating Fields studies. A) Skin safety findings in key studies. B) Recommendations to avoid skin AEs. C) Prevention and management strategies for skin AEs on the scalp, republished from Lacouture et al (2020) Copyright 2020 Lacouture, Anadkat, Ballo, Iwamoto, Jeyapalan, La Rocca, Schwartz, Serventi and Glas. Abbreviations: AE, adverse event; ndGBM, newly diagnosed glioblastoma; rGBM, recurrent glioblastoma.
See this image and copyright information in PMC

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