A review of tumor treating fields (TTFields): advancements in clinical applications and mechanistic insights

Our plain-English summary of A review of tumor treating fields (TTFields): advancements in clinical applications and mechanistic insights, by X. Li, K. Liu, L. Xing, et al (Radiology and Oncology, 2023).

The study

• Authors: X. Li, K. Liu, L. Xing, B. Rubinsky
• Journal: Radiology and Oncology
• Published: 2023;57(3):279-291
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Tumor Treating Fields (TTFields) is a non-invasive modality for cancer treatment that utilizes a specific sinusoidal electric field ranging from 100 kHz to 300 kHz, with an intensity of 1 V/cm to 3 V/cm. Its purpose is to inhibit cancer cell proliferation and induce cell death. Despite promising outcomes from clinical trials, TTFields have received FDA approval for the treatment of glioblastoma multiforme (GBM) and malignant pleural mesothelioma (MPM). Nevertheless, global acceptance of TTFields remains limited. To enhance its clinical application in other types of cancer and gain a better understanding of its mechanisms of action, this review aims to summarize the current research status by examining existing literature on TTFields' clinical trials and mechanism studies.

Conclusions: Through this comprehensive review, we seek to stimulate novel ideas and provide physicians, patients, and researchers with a better comprehension of the development of TTFields and its potential applications in cancer treatment.

© 2023 Xing Li et al., published by Sciendo.

In plain English

This article was a review, not a new study. The authors summarized published clinical trials and laboratory and theoretical studies of Tumor Treating Fields (TTFields), a treatment that applies low-intensity electric fields (1 to 3 V/cm, 100 to 300 kHz) to tumors. The article did not discuss asbestos. For malignant pleural mesothelioma, the review described the STELLAR trial, a single-arm phase II study of 80 patients given TTFields with chemotherapy (pemetrexed plus cisplatin or carboplatin). As reported in the review, median overall survival in that trial was 18.2 months, compared with 12.1 months in historical controls. The only treatment-related toxic effects were mild to moderate dermatitis. The authors noted that these results needed to be confirmed by a randomized trial. They also reported that the FDA approved TTFields for this disease under the Humanitarian Device Exemption pathway on May 23, 2019. The review also covered trials in glioblastoma and in lung, ovarian, pancreatic and liver cancer, several of them still ongoing. The authors concluded that the results were promising but that how TTFields work is still not fully revealed.

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 published clinical trials and mechanism studies of Tumor Treating Fields (no new data collected)
• Who was studied: No study population of its own; the review covered clinical trials of TTFields in glioblastoma multiforme, malignant pleural mesothelioma, non-small cell lung cancer, platinum-resistant ovarian cancer, pancreatic adenocarcinoma and hepatocellular carcinoma, plus laboratory and theoretical mechanism studies
• Exposure: Tumor Treating Fields: low-intensity, intermediate-frequency alternating electric fields used as a cancer treatment. The article does not concern asbestos exposure.
• Main results:
  • STELLAR trial (reported by the review, not done by its authors): a prospective single-arm phase II trial of 80 malignant pleural mesothelioma patients treated with TTFields plus pemetrexed and cisplatin or carboplatin, run from March 2015 to April 2018
  • In STELLAR, median overall survival was 18.2 months compared with 12.1 months in historical controls, and median progression-free survival was 7.6 months compared with 5.7 months in historical controls
  • In STELLAR, the only treatment-related toxic effects were mild to moderate dermatitis
  • The review reported that the FDA approved TTFields for malignant pleural mesothelioma under the Humanitarian Device Exemption pathway on May 23, 2019
  • EF-14 glioblastoma trial (reported by the review): the TTFields plus temozolomide group (466 patients) had a median progression-free survival of 6.7 months and median overall survival of 20.9 months, compared with 4.0 and 16.0 months in the temozolomide-alone group (229 patients)
• The authors' conclusion: The authors concluded that the clinical trial results were promising but that the mechanisms by which TTFields act are still not fully revealed and should be the focus of future research
• Limitations the authors state:
  • The authors noted that the STELLAR mesothelioma trial had a single-arm design and that its results need confirmation in a randomized trial
  • The authors noted that the first glioblastoma pilot trial had no randomized control group and was compared with historical data
  • The authors stated that the link between laboratory observations and proposed mechanisms still needs to be clarified with more rigorous logic

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Tumor Treating Fields (TTFields), Clinical Trial, Pleural Mesothelioma.

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• Advancements and current trends in tumor treating fields: a scientometric analysis — Y. Xing, F. Yasinjan, et al. (2024)
• Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma — D. Chen, S.B. Le, et al. (2022)
• The Mechanisms of Action of Tumor Treating Fields — J.C. Moser, E. Salvador, et al. (2022)
• Tumour treating fields therapy for glioblastoma: current advances and future directions — O. Rominiyi, A. Vanderlinden, et al. (2021)

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