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

Abstract

IntroductionDevelopment 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 analysis80 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 disseminationThis protocol has been approved by the local medical ethical committee (2016-132-f-S). Results will be submitted to international peer-reviewed journals.Trial registrationNCT03377036; Pre-results.

Interval Breast Cancer Rates and Tumor Characteristics in the Prospective Population-based Malmö Breast Tomosynthesis Screening Trial

“…Retrospective trials have shown similar results with no statistically significant differences between interval cancer rates (13,14). To our knowledge, randomized controlled screening trials of DBT with interval cancer rates as end point have not yet published such data (15)(16)(17). In general, interval cancers are more aggressive than screen-detected cancers because they are similar to symptomatic breast cancer in women who are not screened (18).…”

Interval breast cancer rates for digital breast tomosynthesis versus digital mammography population screening: An individual participant data meta-analysis

“…Evidence before this study To address the knowledge gap about interval breast cancer rates for DBT versus mammography screening, and to plan an individual participant data (IPD) meta-analysis, we searched the literature in July 2016 to identify prospective studies that investigated DBT screening and reported data on cancer detection and (potentially) interval cancer data at follow-up; four non-randomised prospective studies met eligibility criteria for our proposed study. Since our initial literature search (using an updated search April 2020) two studies have reported that at follow-up of DBT screening participants Bernardi 2020) there was no significant difference in interval cancer rates between DBT and mammography screening, and two randomised trials (Weigel 2018;Pattacini 2018) have indicated that interval cancer rates will be reported as part of trial outcomes.…”

Accuracy and Effectiveness of Mammography versus Mammography and Tomosynthesis for Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis

“…Another important ongoing clinical trial in this topic is called Digital Breast Tomosynthesis plus Synthesised Images versus Standard Full-Field Digital Mammography in Population-Based Screening (TOSYMA), which is being carried out in Germany. The authors aim to include 80,000 women aged 50 to 69 years who are attending their routine mammography screening programme 73 . The primary endpoints are the detection rate of invasive breast cancers during screening examinations and the cumulative incidence of interval cancers in the two years after a negative examination.…”