Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial

Abstract

Introduction: Development of digital breast tomosynthesis (DBT) provides a technology that generates three-dimensional data sets, thus reducing the pitfalls of overlapping breast tissue. Observational studies suggest that the combination of two-dimensional (2D) digital mammography and DBT increases diagnostic accuracy. However, because of duplicate exposure, this comes at the cost of an augmented radiation dose. This undesired adverse impact can be avoided by using synthesised 2D images reconstructed from the DBT data (s2D).We designed a diagnostic superiority trial on a high level of evidence with the aim of providing a comparison of screening efficacy parameters resulting from DBT+s2D versus the current screening standard 2D full-field digital mammography (FFDM) in a multicentre and multivendor setting on the basis of the quality-controlled, population-based, biennial mammography screening programme in Germany.

Methods and analysis: 80 000 women in the eligible age 50-69 years attending the routine mammography screening programme and willing to participate in the TOSYMA trial will be assigned by 1:1 randomisation to either the intervention arm (DBT+s2D) or the control arm (FFDM) during a 12-month recruitment period in screening units of North Rhine-Westphalia and Lower Saxony. State cancer registries will provide the follow-up of interval cancers.Primary endpoints are the detection rate of invasive breast cancers at screening examination and the cumulative incidence of interval cancers in the 2 years after a negative examination. Secondary endpoints are the detection rate of ductal carcinoma in situ and of tumour size T1, the recall rate for assessment, the positive predictive value of recall and the cumulative 12-month incidence of interval cancers. An adaptive statistical design with one interim analysis provides the option to modify the design.

Ethics and dissemination: This protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer-reviewed journals.

Trial registration: NCT03377036; Pre-results.

Keywords: breast imaging; digital breast tomosynthesis; full-field digital mammography; multicenter randomized controlled trial; population-based screening; synthetic mammography.

Conflict of interest statement

Competing interests: HWH and OH receives third-party funding from the German Federal Office for Radiation Protection (BfS, Bundesamt für Strahlenschutz) for a research project on the evaluation of the German mammography screening program. WH runs the National Mammography Reference Center Münster, a third-party-funded project at the University of Münster, Germany.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1

Flow chart of the screening study. DBT, digital breast tomosynthesis; LS, Lower Saxony; NRW, North Rhine-Westphalia; s2D, synthetic two-dimensional mammogram; 2D-FFDM, two-dimensional full-field digital mammography.

Figure 2

Invasive lobular carcinoma of the right breast depicted by an architectural distortion (A) subtle finding on the two-dimensional full-field digital mammogram (B) pronounced visible on the slice of the digital tomosynthesis as well as on the (C) reconstructed synthetic mammogram.