Tumor treating fields: Will the evidence gap ever be filled?

European Journal of Cancer, vol. 244, pp. 116897

Abstract

Tumor Treating Fields (TTFs) deliver low-intensity electric fields through adhesive skin arrays and have been approved in different oncology indications. However, concerns remain regarding the evidence supporting their benefit. Here, we highlight four limitations. First, TTFields utilization includes 24/7 assistance, home deliveries, and regular home-based interactions for array changes. In the absence of sham-controlled randomized trials, which are the equivalent of placebo-controlled trials for devices, the specific contribution of TTFields cannot be distinguished from the additional supportive care and infrastructure accompanying device use. Second, although a mechanistic rationale exists, the biological plausibility remains limited, particularly because of the lack of validated human in vivo dosimetry data. Third, while reviewing six pivotal randomized trials, we describe the use of suboptimal control arms in half of them, including two trials that reported a survival gain. As a result, it remains unclear whether such a benefit would also be observed in settings with optimal access to contemporary standard-of-care treatments. Fourth, we describe occurrences of protocol changes and unusual censoring patterns, both warranting further examination. The specificities of regulatory pathways for medical devices permit greater evidentiary flexibility than for drugs, while post-market evidence generation remains insufficiently transparent. In contrast to other types of devices, a single company has generated the main evidence base with no substantial replication from competing manufacturers to date. High-quality sham-controlled trials and harmonized post-market obligations are needed to isolate the specific contribution of TTFs and determine the extent to which the observed clinical benefit derives from the device itself as compared with the care surrounding its use. This is particularly relevant in patients with a poor prognosis, as increased clinical attention and supportive care may themselves contribute to improved outcomes.

Authors 5

1. Sruthi Ranganathan

   University of Cambridge

   Affiliation as printed

   School of Clinical Medicine, University of Cambridge, Cambridge, UK

2. Sahar Barjesteh van Waalwijk van Doorn-Khosrovani Aachen

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Medical Oncology, Leiden University Medical Centre, Albinusdreef, Leiden 2333 ZG, the Netherlands; CZ Health Insurance, Ringbaan West 236, Tilburg 5038 KE, the Netherlands

3. Alessandro Hammond

   Harvard University

   Affiliation as printed

   Harvard University, Cambridge, MA, USA

4. Susannah G. Ellsworth

   University of Pittsburgh

   Affiliation as printed

   Department of Radiation Oncology, University of Pittsburgh School of Medicine, PA, USA

5. Timothée Olivier corresponding

   University Hospital of Geneva

   Affiliation as printed

   Department of Oncology, University Hospital Geneva, Switzerland. Electronic address: timothee.olivier@hug.ch