TOSYMA: Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography

Sponsor

University Hospital Muenster (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03377036

Collaborator

German Research Foundation (Other)

99,689

Enrollment

Locations

Arms

80.9

Anticipated Duration (Months)

4747.1

Patients Per Site

58.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Screening	Diagnostic Test: DBT+s2D Diagnostic Test: 2D-FFDM	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

99689 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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)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)

Primary Purpose:

Screening

Official Title:

Prospective Randomized Comparison of Digital Breast Tomosynthesis Plus Synthesized Images Versus Standard Full-field Digital Mammography in Population-based Screening (TOSYMA)

Actual Study Start Date :

Jul 5, 2018

Anticipated Primary Completion Date :

Mar 31, 2025

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DBT+s2D Digital breast tomosynthesis plus synthesized 2D mammograms	Diagnostic Test: DBT+s2D Digital breast tomosynthesis plus synthesized 2D mammograms
Active Comparator: 2D-FFDM 2D full-field digital mammography	Diagnostic Test: 2D-FFDM 2D full-field digital mammography

Arm

Intervention/Treatment

Experimental: DBT+s2D

Digital breast tomosynthesis plus synthesized 2D mammograms

Diagnostic Test: DBT+s2D

Digital breast tomosynthesis plus synthesized 2D mammograms

Active Comparator: 2D-FFDM

2D full-field digital mammography

Diagnostic Test: 2D-FFDM

2D full-field digital mammography

Outcome Measures

Primary Outcome Measures

Detection rate of invasive breast cancers [Routine screening visit]
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 [24 months after routine screening visit]
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) [Routine screening visit]
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 [Routine screening visit]
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 [Routine Screening Visit]
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) [Routine screening visit]
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 [12 months after routine screening visit]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 69 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Screening-Einheit Hannover; Mammographie-Einheit Hannover	Hannover	Niedersachsen	Germany	30449
2	Screening-Einheit Niedersachsen Nordost; Mammographie-Einheit Lüneburg	Lüneburg	Niedersachsen	Germany	21337
3	Screening-Einheit Niedersachsen Nord; Mammographie-Einheit Stade	Stade	Niedersachsen	Germany	21680
4	Screening-Einheit Niedersachsen Mitte; Mammographie-Einheit Vechta	Vechta	Niedersachsen	Germany	49377
5	Screening-Einheit Niedersachsen Nordwest; Mammographie-Einheit Wilhelmshaven	Wilhelmshaven	Niedersachsen	Germany	26382
6	Screening-Einheit Aachen-Düren-Heinsberg; Mammographie-Einheit Aachen	Aachen	Nordrhein-Westfalen	Germany	52062
7	Referenz-Screening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Ahlen	Ahlen	Nordrhein-Westfalen	Germany	59227
8	Screening-Einheit Köln rechtsrheinisch, Leverkusen, Rhein.-Berg. Kreis, Oberbergischer Kreis; Mammographie-Einheit Bergisch Gladbach	Bergisch Gladbach	Nordrhein-Westfalen	Germany	51429
9	Screening-Einheit Bielefeld, Gütersloh; Mammographie-Einheit Bielefeld	Bielefeld	Nordrhein-Westfalen	Germany	33062
10	Screening-Einheit Münster-Süd; Mammographie-Einheit Coesfeld	Coesfeld	Nordrhein-Westfalen	Germany	48653
11	Screening-Einheit Duisburg; Mammographie-Einheit Duisburg	Duisburg	Nordrhein-Westfalen	Germany	47057
12	Screening-Einheit Gelsenkirchen, Kreis Recklinghausen, Bottrop; Mammographie-Einheit Gelsenkirchen	Gelsenkirchen	Nordrhein-Westfalen	Germany	45894
13	Screening-Einheit Minden-Lübbecke, Herford; Mammographie-Einheit Herford	Herford	Nordrhein-Westfalen	Germany	32052
14	Screening-Einheit Mönchengladbach, Krefeld, Viersen; Mammographie-Einheit Krefeld	Krefeld	Nordrhein-Westfalen	Germany	47805
15	Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Lippstadt	Lippstadt	Nordrhein-Westfalen	Germany	59555
16	Referenz-Screeening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Münster-Nord	Münster	Nordrhein-Westfalen	Germany	48143
17	Screening-Einheit Münster-Süd; Mammographie-Einheit Münster	Münster	Nordrhein-Westfalen	Germany	48153
18	Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Paderborn	Paderborn	Nordrhein-Westfalen	Germany	33098
19	Screening-Einheit Märkischer Kreis, Hamm, Unna; Mammographie-Einheit Schwerte	Schwerte	Nordrhein-Westfalen	Germany	58239
20	Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Solingen-Mitte	Solingen	Nordrhein-Westfalen	Germany	42651
21	Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Wuppertal-Elberfeld	Wuppertal	Nordrhein-Westfalen	Germany	42109