Clinical trial NCT03377036: Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography
Official title: Prospective Randomized Comparison of Digital Breast Tomosynthesis Plus Synthesized Images Versus Standard Full-field Digital Mammography in Population-based Screening (TOSYMA)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer Screening
Keywords: Breast Cancer
Population-based Screening
Digital Breast Tomosynthesis plus synthesized Mammography
Reconstructed Mammography
Full-Field Digital Mammography (FFDM)
Multicentric Randomized Controlled Trial
Diagnostic Performance
Recall Rate
Interval Cancer
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2017-12-19
Enrollment: 99689
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to either Digital Breast Tomosynthesis plus synthesized 2D mammograms (DBT+s2D) or 2D Full-Field Digital Mammography (2D-FFDM)
Primary purpose: SCREENING

Brief summary: This study is a randomized, multicenter, multivendor, controlled, diagnostic superiority trial to compare digital breast tomosynthesis plus synthesized 2D mammograms (DBT+s2D) versus standard 2D full-field digital mammography (2D-FFDM) regarding the effectiveness as screening modality.

Detailed description: The primary objective of the study is to evaluate whether digital breast tomosynthesis plus synthesized 2D mammograms leads to a relevant increase in the detection rate of screening-detected invasive cancers compared to 2D full-field digital mammography in routine screening according to the European Guidelines. Furthermore, the incidence rate of interval cancers within a 24 months interval after screening will be compared between both study arms in order to investigate the potential for overdiagnosis.

According to the pre-defined order of both primary endpoints and the primary objective of the study in the planning phase, the initial sample size calculation was based solely on the first primary endpoint (invasive breast cancer detection rate). Given the increasing national and international attention of interval cancers to assess the impact of potential overdiagnosis caused by tomosynthesis, we have planned a sample size increase from 80,000 to 120,000 study participants to achieve a reasonable statistical power for the evaluation of both primary endpoints. The revised sample size calculation was carried out without knowledge of the data from the currently recruiting TOSYMA study, i.e. all planning assumptions were based on external data that do not belong to the ongoing study.

Eligibility criteria: Inclusion Criteria:

* Women eligible to participate in the National Mammography Screening Program of Germany
* Informed decision for mammography screening
* Written informed consent
* No prior participation in the TOSYMA trial

Exclusion Criteria:

* Breast cancer up to 5 years prior to study invitation
* Previous mammography examination \< 12 months,
* Breast implants

Primary outcomes:
measure: Detection rate of invasive breast cancers
timeFrame: Routine screening visit
measure: Cumulative 24 months incidence of interval cancers
timeFrame: 24 months after routine screening visit
Secondary outcomes:
measure: Detection rate of ductal carcinoma in situ (DCIS)
timeFrame: Routine screening visit
measure: Detection rate of tumor category pT1
timeFrame: Routine screening visit
measure: Recall rate for further assessment
timeFrame: Routine Screening Visit
measure: Positive predictive value of recall for further assessment (PPV1)
timeFrame: Routine screening visit
measure: Cumulative 12 months incidence of interval cancers
timeFrame: 12 months after routine screening visit
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Screening-Einheit Hannover; Mammographie-Einheit Hannover
state: Niedersachsen
city: Lüneburg
country: Germany
facility: Screening-Einheit Niedersachsen Nordost; Mammographie-Einheit Lüneburg
state: Niedersachsen
city: Stade
country: Germany
facility: Screening-Einheit Niedersachsen Nord; Mammographie-Einheit Stade
state: Niedersachsen
city: Vechta
country: Germany
facility: Screening-Einheit Niedersachsen Mitte; Mammographie-Einheit Vechta
state: Niedersachsen
city: Wilhelmshaven
country: Germany
facility: Screening-Einheit Niedersachsen Nordwest; Mammographie-Einheit Wilhelmshaven
state: Niedersachsen
city: Aachen
country: Germany
facility: Screening-Einheit Aachen-Düren-Heinsberg; Mammographie-Einheit Aachen
state: Nordrhein-Westfalen
city: Ahlen
country: Germany
facility: Referenz-Screening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Ahlen
state: Nordrhein-Westfalen
city: Bergisch Gladbach
country: Germany
facility: Screening-Einheit Köln rechtsrheinisch, Leverkusen, Rhein.-Berg. Kreis, Oberbergischer Kreis; Mammographie-Einheit Bergisch Gladbach
state: Nordrhein-Westfalen
city: Bielefeld
country: Germany
facility: Screening-Einheit Bielefeld, Gütersloh; Mammographie-Einheit Bielefeld
state: Nordrhein-Westfalen
city: Coesfeld
country: Germany
facility: Screening-Einheit Münster-Süd; Mammographie-Einheit Coesfeld
state: Nordrhein-Westfalen
city: Duisburg
country: Germany
facility: Screening-Einheit Duisburg; Mammographie-Einheit Duisburg
state: Nordrhein-Westfalen
city: Gelsenkirchen
country: Germany
facility: Screening-Einheit Gelsenkirchen, Kreis Recklinghausen, Bottrop; Mammographie-Einheit Gelsenkirchen
state: Nordrhein-Westfalen
city: Herford
country: Germany
facility: Screening-Einheit Minden-Lübbecke, Herford; Mammographie-Einheit Herford
state: Nordrhein-Westfalen
city: Krefeld
country: Germany
facility: Screening-Einheit Mönchengladbach, Krefeld, Viersen; Mammographie-Einheit Krefeld
state: Nordrhein-Westfalen
city: Lippstadt
country: Germany
facility: Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Lippstadt
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Referenz-Screeening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Münster-Nord
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Screening-Einheit Münster-Süd; Mammographie-Einheit Münster
state: Nordrhein-Westfalen
city: Paderborn
country: Germany
facility: Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Paderborn
state: Nordrhein-Westfalen
city: Schwerte
country: Germany
facility: Screening-Einheit Märkischer Kreis, Hamm, Unna; Mammographie-Einheit Schwerte
state: Nordrhein-Westfalen
city: Solingen
country: Germany
facility: Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Solingen-Mitte
state: Nordrhein-Westfalen
city: Wuppertal
country: Germany
facility: Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Wuppertal-Elberfeld
state: Nordrhein-Westfalen
Study officials:
affiliation: University Clinic for Radiology, University of Muenster / University Hospital Muenster
name: Walter Heindel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weigel S, Gerss J, Hense HW, Krischke M, Sommer A, Czwoydzinski J, Lenzen H, Kerschke L, Spieker K, Dickmaenken S, Baier S, Urban M, Hecht G, Heidinger O, Kieschke J, Heindel W. Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial. BMJ Open. 2018 May 14;8(5):e020475. doi: 10.1136/bmjopen-2017-020475.
citation: Weigel S, Heindel W, Hense HW, Decker T, Gerss J, Kerschke L; TOSYMA Screening Trial Study Group. Breast Density and Breast Cancer Screening with Digital Breast Tomosynthesis: A TOSYMA Trial Subanalysis. Radiology. 2023 Feb;306(2):e221006. doi: 10.1148/radiol.221006. Epub 2022 Oct 4.
citation: Heindel W, Weigel S, Gerss J, Hense HW, Sommer A, Krischke M, Kerschke L; TOSYMA Screening Trial Study Group. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022 May;23(5):601-611. doi: 10.1016/S1470-2045(22)00194-2. Epub 2022 Apr 12.