Tumour treating fields therapy for glioblastoma: current advances and future directions

Our plain-English summary of Tumour treating fields therapy for glioblastoma: current advances and future directions, by O. Rominiyi, A. Vanderlinden, S.J. Clenton, et al (British Journal of Cancer, 2021).

The study

• Authors: O. Rominiyi, A. Vanderlinden, S.J. Clenton, C. Bridgewater, Y. Al-Tamimi, S.J. Collis
• Journal: British Journal of Cancer
• Published: 2021;124(4):697-709
• Type of article: Review
• Cited by: 244 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.

In plain English

This article was a review, not an original study, and it did not deal with asbestos exposure. The authors described tumour treating fields (TTFields), a treatment that delivers low-intensity, intermediate-frequency alternating electric fields through arrays placed on the skin. They reviewed laboratory research on how it may act against cancer cells, and clinical trials across several cancers, mainly glioblastoma. Among the trials they summarised, the EF-14 trial in newly diagnosed glioblastoma reported median overall survival of 20.9 months with TTFields plus temozolomide versus 16.0 months with temozolomide alone. For mesothelioma, the authors described a separate published trial, STELLAR. It was a single-arm Phase 2 trial in patients with unresectable malignant pleural mesothelioma given TTFields plus chemotherapy. It reported median overall survival of 18.2 months and progression-free survival of 7.6 months, against 12.1 and 5.7 months for historical controls given chemotherapy only. TTFields then received FDA approval for this use under a humanitarian device exemption. The authors concluded that TTFields has great potential to improve outcomes. They noted that its effects remain incompletely understood.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of preclinical (laboratory and animal) research and clinical trials of tumour treating fields therapy, focused on glioblastoma
• Who was studied: No study population of its own; the authors summarised published preclinical studies and clinical trials of TTFields across various cancers
• Exposure: No asbestos exposure was studied. The subject was a treatment, TTFields: low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz) alternating electric fields delivered through arrays on the skin
• Main results:
  • Reviewed trial (EF-14), newly diagnosed glioblastoma: median overall survival was 20.9 months with TTFields plus temozolomide versus 16.0 months with temozolomide alone
  • Reviewed trial (EF-11), recurrent glioblastoma: there was no significant difference between TTFields and chemotherapy in overall survival (6.6 vs 6.0 months) or progression-free survival (2.2 vs 2.1 months)
  • Reviewed trial (STELLAR) was a single-arm Phase 2 trial in patients with unresectable, treatment-naive malignant pleural mesothelioma, giving TTFields with standard chemotherapy
  • In STELLAR, median overall survival was 18.2 months and median progression-free survival was 7.6 months
  • The STELLAR results were compared with overall survival of 12.1 months and progression-free survival of 5.7 months in historical controls given standard chemotherapy only
  • After STELLAR, TTFields received FDA approval in combination with chemotherapy for malignant pleural mesothelioma under a humanitarian device exemption
  • Laboratory studies reviewed by the authors suggested that TTFields affect several biological processes beyond cell division
• The authors' conclusion: The authors concluded that TTFields has great potential, both in the short and long term, to improve outcomes for many patients with a range of cancers
• Limitations the authors state:
  • The authors stated that the range of effects TTFields produces remains incompletely understood
  • The authors stated that the review could not comment in detail on each trial it listed

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Clinical Trial.

Related studies

• Role of Klotho Protein in Tumor Genesis, Cancer Progression, and Prognosis in Patients with High-Grade Glioma — N. Peshes-Yeloz, L. Ungar, et al. (2019)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• Tumour Treating Fields for mesothelioma: controversy versus opportunity — D.A. Fennell (2019)
• Tumour Treating Fields for mesothelioma — M. Barbarino, M. Bottaro, et al. (2020)
• Tumour Treating Fields for mesothelioma - Authors' reply — G.L. Ceresoli, L. Gianoncelli, et al. (2020)
• Tumour Treating Fields for mesothelioma — C.J. de Gooijer, J.A. Burgers (2020)

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