Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography (TOSYMA)
Primary Purpose
Breast Cancer Screening
Status
Active
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
DBT+s2D
2D-FFDM
Sponsored by
About this trial
This is an interventional screening trial for Breast Cancer Screening focused on measuring 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
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
Sites / Locations
- Screening-Einheit Hannover; Mammographie-Einheit Hannover
- Screening-Einheit Niedersachsen Nordost; Mammographie-Einheit Lüneburg
- Screening-Einheit Niedersachsen Nord; Mammographie-Einheit Stade
- Screening-Einheit Niedersachsen Mitte; Mammographie-Einheit Vechta
- Screening-Einheit Niedersachsen Nordwest; Mammographie-Einheit Wilhelmshaven
- Screening-Einheit Aachen-Düren-Heinsberg; Mammographie-Einheit Aachen
- Referenz-Screening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Ahlen
- Screening-Einheit Köln rechtsrheinisch, Leverkusen, Rhein.-Berg. Kreis, Oberbergischer Kreis; Mammographie-Einheit Bergisch Gladbach
- Screening-Einheit Bielefeld, Gütersloh; Mammographie-Einheit Bielefeld
- Screening-Einheit Münster-Süd; Mammographie-Einheit Coesfeld
- Screening-Einheit Duisburg; Mammographie-Einheit Duisburg
- Screening-Einheit Gelsenkirchen, Kreis Recklinghausen, Bottrop; Mammographie-Einheit Gelsenkirchen
- Screening-Einheit Minden-Lübbecke, Herford; Mammographie-Einheit Herford
- Screening-Einheit Mönchengladbach, Krefeld, Viersen; Mammographie-Einheit Krefeld
- Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Lippstadt
- Referenz-Screeening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Münster-Nord
- Screening-Einheit Münster-Süd; Mammographie-Einheit Münster
- Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Paderborn
- Screening-Einheit Märkischer Kreis, Hamm, Unna; Mammographie-Einheit Schwerte
- Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Solingen-Mitte
- Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Wuppertal-Elberfeld
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
DBT+s2D
2D-FFDM
Arm Description
Digital breast tomosynthesis plus synthesized 2D mammograms
2D full-field digital mammography
Outcomes
Primary Outcome Measures
Detection rate of invasive breast cancers
Number of women with screening-detected invasive breast cancer divided by the number of all women screened. A screening-detected breast cancer is classified as invasive carcinoma if the pT category (pathological tumor size) of the TNM classification falls into one of the following categories: pT1mic, pT1a, pT1b, pT1c, pT1, pT2, pT3, pT4a, pT4b, pT4c, pT4d, pT4, pTX (for evaluation purpose pTX defines histologically approved invasive breast cancer with missing tumor diameter) or the final pathological categorization has been done after neoadjuvant therapy (ypT), implying an invasive cancer prior to therapy.
Cumulative 24 months incidence of interval cancers
The 24 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 24 months interval after a negative screening examination divided by the number of all women with a negative screening result.
Secondary Outcome Measures
Detection rate of ductal carcinoma in situ (DCIS)
Number of women with screening-detected ductal carcinoma in situ (if the pT category of the TNM classification falls into the category pTis) divided by the number of all women screened.
Detection rate of tumor category pT1
Number of women with screening-detected invasive breast cancers of the category pT1 divided by the number of all women screened. A screening-detected breast cancer is classified as breast cancer of tumor category pT1 if tumor size is ≤ 20 mm in greatest dimension and the respective pT subcategory of the pTNM classification is one of the following: pT1mic, pT1a, pT1b, pT1c, pT1.
Recall rate for further assessment
Number of women with recalls for further assessment divided by the number of all women screened.
Positive predictive value of recall for further assessment (PPV1)
Number of women with screening-detected malignancies (ductal carcinoma in situ or invasive breast cancer) divided by the number of women with recalls for further assessment.
Cumulative 12 months incidence of interval cancers
The 12 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 12 months interval after a negative screening examination divided by the number of all women with a negative screening result.
Full Information
NCT ID
NCT03377036
First Posted
December 13, 2017
Last Updated
March 16, 2022
Sponsor
University Hospital Muenster
Collaborators
German Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT03377036
Brief Title
Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography
Acronym
TOSYMA
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
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 5, 2018 (Actual)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Muenster
Collaborators
German Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
99689 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DBT+s2D
Arm Type
Experimental
Arm Description
Digital breast tomosynthesis plus synthesized 2D mammograms
Arm Title
2D-FFDM
Arm Type
Active Comparator
Arm Description
2D full-field digital mammography
Intervention Type
Diagnostic Test
Intervention Name(s)
DBT+s2D
Intervention Description
Digital breast tomosynthesis plus synthesized 2D mammograms
Intervention Type
Diagnostic Test
Intervention Name(s)
2D-FFDM
Intervention Description
2D full-field digital mammography
Primary Outcome Measure Information:
Title
Detection rate of invasive breast cancers
Description
Number of women with screening-detected invasive breast cancer divided by the number of all women screened. A screening-detected breast cancer is classified as invasive carcinoma if the pT category (pathological tumor size) of the TNM classification falls into one of the following categories: pT1mic, pT1a, pT1b, pT1c, pT1, pT2, pT3, pT4a, pT4b, pT4c, pT4d, pT4, pTX (for evaluation purpose pTX defines histologically approved invasive breast cancer with missing tumor diameter) or the final pathological categorization has been done after neoadjuvant therapy (ypT), implying an invasive cancer prior to therapy.
Time Frame
Routine screening visit
Title
Cumulative 24 months incidence of interval cancers
Description
The 24 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 24 months interval after a negative screening examination divided by the number of all women with a negative screening result.
Time Frame
24 months after routine screening visit
Secondary Outcome Measure Information:
Title
Detection rate of ductal carcinoma in situ (DCIS)
Description
Number of women with screening-detected ductal carcinoma in situ (if the pT category of the TNM classification falls into the category pTis) divided by the number of all women screened.
Time Frame
Routine screening visit
Title
Detection rate of tumor category pT1
Description
Number of women with screening-detected invasive breast cancers of the category pT1 divided by the number of all women screened. A screening-detected breast cancer is classified as breast cancer of tumor category pT1 if tumor size is ≤ 20 mm in greatest dimension and the respective pT subcategory of the pTNM classification is one of the following: pT1mic, pT1a, pT1b, pT1c, pT1.
Time Frame
Routine screening visit
Title
Recall rate for further assessment
Description
Number of women with recalls for further assessment divided by the number of all women screened.
Time Frame
Routine Screening Visit
Title
Positive predictive value of recall for further assessment (PPV1)
Description
Number of women with screening-detected malignancies (ductal carcinoma in situ or invasive breast cancer) divided by the number of women with recalls for further assessment.
Time Frame
Routine screening visit
Title
Cumulative 12 months incidence of interval cancers
Description
The 12 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 12 months interval after a negative screening examination divided by the number of all women with a negative screening result.
Time Frame
12 months after routine screening visit
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Heindel, MD, PhD
Organizational Affiliation
University Clinic for Radiology, University of Muenster / University Hospital Muenster
Official's Role
Principal Investigator
Facility Information:
Facility Name
Screening-Einheit Hannover; Mammographie-Einheit Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30449
Country
Germany
Facility Name
Screening-Einheit Niedersachsen Nordost; Mammographie-Einheit Lüneburg
City
Lüneburg
State/Province
Niedersachsen
ZIP/Postal Code
21337
Country
Germany
Facility Name
Screening-Einheit Niedersachsen Nord; Mammographie-Einheit Stade
City
Stade
State/Province
Niedersachsen
ZIP/Postal Code
21680
Country
Germany
Facility Name
Screening-Einheit Niedersachsen Mitte; Mammographie-Einheit Vechta
City
Vechta
State/Province
Niedersachsen
ZIP/Postal Code
49377
Country
Germany
Facility Name
Screening-Einheit Niedersachsen Nordwest; Mammographie-Einheit Wilhelmshaven
City
Wilhelmshaven
State/Province
Niedersachsen
ZIP/Postal Code
26382
Country
Germany
Facility Name
Screening-Einheit Aachen-Düren-Heinsberg; Mammographie-Einheit Aachen
City
Aachen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
52062
Country
Germany
Facility Name
Referenz-Screening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Ahlen
City
Ahlen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
59227
Country
Germany
Facility Name
Screening-Einheit Köln rechtsrheinisch, Leverkusen, Rhein.-Berg. Kreis, Oberbergischer Kreis; Mammographie-Einheit Bergisch Gladbach
City
Bergisch Gladbach
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
51429
Country
Germany
Facility Name
Screening-Einheit Bielefeld, Gütersloh; Mammographie-Einheit Bielefeld
City
Bielefeld
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
33062
Country
Germany
Facility Name
Screening-Einheit Münster-Süd; Mammographie-Einheit Coesfeld
City
Coesfeld
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48653
Country
Germany
Facility Name
Screening-Einheit Duisburg; Mammographie-Einheit Duisburg
City
Duisburg
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
47057
Country
Germany
Facility Name
Screening-Einheit Gelsenkirchen, Kreis Recklinghausen, Bottrop; Mammographie-Einheit Gelsenkirchen
City
Gelsenkirchen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45894
Country
Germany
Facility Name
Screening-Einheit Minden-Lübbecke, Herford; Mammographie-Einheit Herford
City
Herford
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
32052
Country
Germany
Facility Name
Screening-Einheit Mönchengladbach, Krefeld, Viersen; Mammographie-Einheit Krefeld
City
Krefeld
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
47805
Country
Germany
Facility Name
Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Lippstadt
City
Lippstadt
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
59555
Country
Germany
Facility Name
Referenz-Screeening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Münster-Nord
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48143
Country
Germany
Facility Name
Screening-Einheit Münster-Süd; Mammographie-Einheit Münster
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48153
Country
Germany
Facility Name
Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Paderborn
City
Paderborn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
33098
Country
Germany
Facility Name
Screening-Einheit Märkischer Kreis, Hamm, Unna; Mammographie-Einheit Schwerte
City
Schwerte
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
58239
Country
Germany
Facility Name
Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Solingen-Mitte
City
Solingen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
42651
Country
Germany
Facility Name
Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Wuppertal-Elberfeld
City
Wuppertal
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
42109
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29764880
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.
Results Reference
background
PubMed Identifier
36194110
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.
Results Reference
derived
PubMed Identifier
35427470
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.
Results Reference
derived
Links:
URL
http://bmjopen.bmj.com/content/8/5/e020475
Description
BMJ Open
Learn more about this trial
Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography
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