Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Vasoconstrictor Agents

Respiratory System Agents

All Drugs and Chemicals

Epinephrine

Racepinephrine

Epinephryl borate

Digital breast tomosynthesis plus synthesized 2D mammograms

DBT+s2D

2D-FFDM

Walter Heindel, MD, PhD

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.

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.

Participants will be randomized to either Digital Breast Tomosynthesis plus synthesized 2D mammograms (DBT+s2D) or 2D Full-Field Digital Mammography (2D-FFDM)

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

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

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.

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.

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.

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.

Number of women with recalls for further assessment divided by the number of all women screened.

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.

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.

German Research Foundation

University Hospital Muenster

Technetium Tc 99m Sestamibi

Subjects who have had mammography less than two years ago will receive MBI and breast ultrasound only. Other participants will receive three interventions including molecular breast imaging, mammography and breast ultrasound. The interval between each examination will be less than 6 months.

Molecular breast imaging will be performed at 5-10 minutes after intravenous injection of 15-20 millicurie (mCi) Tc-99m sestamibi. Both craniocaudal (CC) view and mediolateral oblique (MLO) images of the breast are taken.

Molecular breast imaging

During the procedure, the breast is compressed using a dedicated mammography unit. Parallel-plate compression evens out the thickness of breast tissue to increase image quality by reducing the thickness of tissue that x-rays must penetrate, decreasing the amount of scattered radiation, reducing the required radiation dose, and holding the breast still (preventing motion blur). Both craniocaudal (CC) view and mediolateral oblique (MLO) images of the breast are taken.

Mammography

Ultrasound investigation of breast is performed by members of breast cancer team. If abnormality is found by the procedure, biopsy will not be performed directly.

Breast ultrasound

The molecular breast imaging (MBI) is a potential modality to screen breast cancer. In this study, we compare and evaluate the recall rate/diagnostic efficiency of MBI, mammography and breast sonography, and aim to determine best ways of breast cancer screening.

Keywords: molecular breast imaging, MBI, breast cancer, mammography, sonography

1. Background: In breast cancer screening, the sensitivity of mammography is about 71-96 %, but the sensitivity decreases in the three following groups: (1) under 50 years old; (2) dense breast parenchyma; (3) higher risk of breast cancer. The Health and Welfare Ministry data in recent 2 years showed Taiwanese women accepted mammography for screening in the ratio of only about 36%, representing many missed opportunities for early detection. One reason to reject mammography may be the discomfort caused by compression. To solve the above mammography possible weakness, other screening methods came into being, such as molecular breast imaging (MBI) of nuclear medicine. Radiotracer of Tc-99m sestamibi was found for targeting breast tumor 20 years ago, and approved by the FDA in 1997. However, the application is limited due to the suboptimal scanning camera design. Ten years later, the Mayo Clinics developed MBI technology, using small-sized semiconductor detectors. Then it become possible that the nuclear technologist have patient's breast tissue fit the detector in almost the same fashion of mammography without heavy compression.
2. Objective: The aim of this study is to evaluate the recall rate and diagnostic accuracy of MBI, mammography and breast echo, for female population.
3. Study design: Female patients referred to Nuclear Medicine Department for myocardial perfusion scan will be recruited in this study. It is because that MBI and myocardial perfusion scan share the same radiotracer. Then MBI will become additional scanning only. About 1800 female subjects will involve, and further mammography and/or breast sonography will be arranged within 6 months after MBI. Participants will be encouraged to receive mammography every 2 years and telephone survey. We hope that this study will help us to compare and evaluate the recall rate/diagnostic efficiency of MBI, mammography and breast sonography, and to determine best ways of breast cancer screening.

Molecular Breast Imaging in Screening Breast Cancer

The frequency with which a radiologist or physician interprets findings of an examination as positive

The sensitivity, specificity, positive predictive value and negative predictive value of each imaging modality

Chang Gung Memorial Hospital

18200 participants who will be screened with tomosynthesis instead of digital mammography. All participants will be asked to participate in the study for 2 screening rounds. The number of participants for the second round will be less, due to drop-outs.

Screening with Digital Breast Tomosynthesis instead of Digital Mammography, for two screening rounds

Digital Breast Tomosynthesis

Mireille Broeders, Prof.

Ioannis Sechopoulos, Prof.

Nicolien van Ravesteyn, PhD

Digital breast tomosynthesis (DBT) creates a digital pseudo- three-dimensional image of the breast similar to mammography. This gives the screening radiologist more information about a possible abnormality. As a result, breast cancer can be found earlier, but more women might need to be recalled.

In the STREAM study, the aim is to identify the impact of DBT on the screen-detected cancer and recall rates, and on interval and advanced cancer rates in 18,200 women after two rounds of screening. For comparison, a control group of about 86,400 women will be selected from the database of the national screening program. Women, screening radiographers, and screening radiologists will be asked whether they find this new screening technique acceptable. Furthermore, the optimal strategy for screening radiologists to read the DBT images will be identified and the cost-effectiveness of screening with DBT will be determined. The images and data will be stored in a database for future research.

Expected outcome:

As a result of this project, the researchers will have shown if breast cancer screening with DBT in the Netherlands should be implemented or not. It will also be demonstrated, were it to be introduced, how it should be implemented, having addressed all the remaining questions, and having found the optimal DBT workflow specifically for a high-volume population-based screening program.

In the last decade, several large-scale European studies have shown that digital breast tomosynthesis (DBT) increases the detection rate from \~6 to \~9 cancers per 1000 women screened, while the recall rate approaches 3.5% to 4%, independent of the initial recall rate. In the Dutch screening setting with digital mammography (DM), the recall rate is only 2.4%. Therefore, introducing DBT in the Netherlands will likely generate an increase in false positives, but the magnitude of this increase is unknown.

Furthermore, the \~50x increase in the number of images resulting from a DBT exam compared to a DM exam doubles the reading time. For DBT screening in the Netherlands to be feasible from the economic and human resources point of view, the interpretation of these cases must be accelerated, to result in an average reading time comparable to that of reviewing DM exams.

The aim of this project is to make the replacement of DM with DBT in the Dutch National Breast Cancer Screening Program feasible and sustainable, by ensuring its acceptability by the various stakeholders, optimizing the acquisition and reading strategy, determining its expected impact on the national recall rate, and determining its cost-effectiveness. In addition, completion of this project will result in the creation of a DBT-based screening database available for future research.

Work Package (WP) 1 will involve the introduction of DBT in 6 of the 71 screening units in the country to screen 18,200 women for two screening rounds. This study is powered to detect a combined one-third reduction in the interval and advanced cancer rates with DBT screening as the primary endpoint. In addition, as secondary endpoints, the Dutch DBT-based screening recall rates will be determined for the first and second rounds of DBT screening. A contemporary control group of about 86,400 women screened with DM will be selected from the screening database (ScreenIT) of the national screening program. This control group will be selected to reflect the distribution of urban and rural areas as well as the mixture of mobile and fixed units of the screening units selected for the intervention group. In addition, the attendees, and the screening radiographers and radiologists will be surveyed to identify any barriers that limit acceptability of this new modality. Finally, WP1 will also involve the creation of a DBT-based screening database for further research.

In WP2, the optimal DBT reading strategy to be used in the Dutch screening program to minimize the increase in reading time with DBT, will be identified. For this, retrospective observer studies will be performed, using the images from WP1, to test eight different acquisition and reading strategies, some involving the use of cutting-edge artificial intelligence computer systems. These strategies have been shown in initial studies, many performed by the sponsor, to result in a significant reduction in reading time, with no or minimal loss in performance. Once the optimal reading strategies is identified, it will be used to interpret the entire second round of DBT screening acquired in WP1 at the screening reading units retrospectively. In this way, its actual performance and impact on reading time in the real screening environment will be determined.

Finally, in WP3, the results from the other two WPs will be used to model the entire DBT screening program and therefore predict the long-term outcomes and cost-effectiveness of this new screening program. The only method possible to estimate the impact of screening on long-term effects, such as breast cancer mortality and morbidity, as well as cost-effectiveness, is the use of modelling. Therefore, the well-validated MISCAN model will be used, with the data and results gathered, to estimate the long-term impact of DBT screening.

As a result of this project, if successful, breast cancer screening with DBT will be ready for nationwide implementation, having addressed all the country-specific questions and having optimized the DBT workflow specifically for a high-volume population-based screening program.

Digital Breast Tomosynthesis for the Dutch National Breast Cancer Screening Program

The following end products will be made available for further research and verification:

* Summary outcomes of the screening
* Methods used during the study such as, but not limited to, data extraction algorithms, statistical analysis, and cost effectiveness

The outcome will be compared to the control group (DM)

The outcome will be calculated for the intervention group (DBT) and the control group (DM):

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography	NCT03377036	Breast Cancer S...	DBT+s2D 2D-FFDM	50 Years - 69 Years	University Hospital Muenster
Molecular Breast Imaging in Screening Breast Cancer	NCT03082456	Breast Cancer	Molecular breas... Mammography Breast ultrasou...	45 Years - 69 Years	Chang Gung Memorial Hospital
Digital Breast Tomosynthesis for the Dutch National Breast Cancer Screening Program	NCT06059300	Breast Cancer S...	Digital Breast ...	50 Years - 72 Years	Radboud University Medical Center
Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography	NCT03377036	Breast Cancer S...	DBT+s2D 2D-FFDM	50 Years - 69 Years	University Hospital Muenster

Spots Global Cancer Trial Database for recall rate

Every month we try and update this database with for recall rate cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for recall rate

Every month we try and update this database with for recall rate cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for recall rate cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.