Efficacy of Digital Breast Tomosynthesis (DBT) in Addition to Standard 2- Dimensional Mammography in Evaluating Extent of Disease in Newly Diagnosed Breast Cancer Patients
Phase: NA
Conditions: Breast Cancer
Sponsor: Case Comprehensive Cancer Center

 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY NUMBER: CASE 6117  
 
ClinicalTrials.gov NCT #: NCT03190083 
 
Protocol Date:  2/15/2019 
 
STUDY TITLE:  Efficacy of Digital Breast Tomosynthesis (DBT) in Addition to Standard 2- 
Dimensional Mammography in Evaluating Extent of Disease in Newly Diagnosed Breast Cancer 
Patients 
 
 
 
 
PRINCIPAL INVESTIGATOR: Nidhi Sharma, MD 
 
 
 
 
Cleveland Clinic  
 
 
 
 
Imaging Institute 
 
 
 
 
 
Breast Imaging, Department of Diagnostic Radiology 
 
 
 
 
9500 Euclid Avenue A-10  
 
 
 
 
 
 
Cleveland, OH 44195 
 
 
 
 
  
 
 
 
 
 
 
 
 
CO- INVESTIGATOR:  
 
Dana Ataya, M.D, Cleveland Clinic, Breast Imaging, Department of Diagnostic Radiology 
Laura Shepardson, M.D Cleveland Clinic, Breast Imaging, Department of Diagnostic Radiology,  
Leah K Sieck, M.D. Cleveland Clinic, Breast Imaging, Department of Diagnostic Radiology 
 
STATISTICIAN:  
 
Nancy Obuchowski, PhD  
 
 
 
 
Case Comprehensive Cancer Center 
 
 
 
 
Cleveland Clinic 
 
 
 
 
9500 Euclid Avenue  
 
 
 
 
 
 
 
Cleveland, OH 44195  
 
 
 
 
 
 
  
 
 
 
 
 
 
STUDY COORDINATOR: 
 
 
 
 
 
 
 
 
 
 
 
 

 
CASE 6117 
Page 2 
Version date: 02/15/2019 
 
 
  
 
 
 
 
 
 
 
 
 
SPONSOR:  
 
 
Case Comprehensive Cancer Center  
 
 
 
 
 
 
SUPPORT/FUNDING: 
 
Taussig Cancer Center research grant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
CASE 6117 
Page 3 
Version date: 02/15/2019 
 
 
PROTOCOL SUMMARY 
 
Protocol Number/Title 
 CASE 6117 Efficacy of digital breast tomosynthesis 
(DBT) 
in 
addition 
to 
standard 
2- 
dimensional 
mammography in evaluating extent of disease in newly 
diagnosed breast cancer patients 
Study Phase 
N/A  
Brief Background/Rationale
 
 
 
The proposed project aims at impacting a large set of 
population of women with newly diagnosed breast cancer. 
One in every eight women is diagnosed with breast cancer 
in their lifetime (10). The study aims at comparing the role 
of DBT in addition to standard 2-D mammograms in all 
new breast cancer patients to assess for improved detection 
of the extent of the cancer and additional imaging findings 
that can impact surgical planning and treatment. Given the 
significance of the study, this may change the standard of 
care and practice at our institution. 
Primary Objective  
The primary objective of the study is to measure the 
frequency with which DBT alters the surgical plan.  Only 
positive findings, like an additional site of cancer or  DCIS 
(findings requiring surgical intervention), will be taken into 
account when estimating the frequency of changes to 
surgical management. 
Secondary Objective(s) 
Secondary Endpoint(s) 
Exploratory Objective(s) 
1.To measure the frequency and nature of additional 
findings like atypical pathology (atypical ductal/lobular 
hyperplasia, papilloma, LCIS) found on DBT. 
2.To identify variables on 2D (e.g. dense breasts, 
architectural distortions, non-calcified masses) that might 
predict which patients would benefit from DBT. 
3.To measure the proportion of patients undergoing 
additional work-up following the DBT, and the subset of 
these patients with benign findings (i.e. False Positives). 
 
Sample Size 
Enrollment goal - 150 
Age - 25-85 years , gender - female 
Disease sites/Conditions 
Breast Cancer 
Interventions 
3dimensional tomosynthesis mammogram 
 
 
 
 
 
 

 
CASE 6117 
Page 4 
Version date: 02/15/2019 
 
ABBREVIATIONS  
 
 
 
 
CCCC Case Comprehensive Cancer Center 
CRF 
Case Report Form 
DCRU Dahm’s Clinical Research Unit 
DSTC 
Data Safety and Toxicity Committee 
FDA 
Food and Drug Administration 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
PRMC Protocol Review and Monitoring Committee
SOC 
Standard of Care 
CCF 
Cleveland Clinic Foundation 
UH 
University Hospitals 
 
 

 
CASE 6117 
Page 5 
Version date: 02/15/2019 
 
TABLE OF CONTENTS 
 
1.0  
INTRODUCTION  
 
1.1 
Background/Rationale 
 
2.0 
OBJECTIVES 
2.1 
Primary Objective 
 
2.2  
Secondary Objective(s) 
 
3.0 
STUDY DESIGN 
 
4.0 
Inclusion Criteria/Exclusion Criteria 
4.1 
Inclusion of Women and Minorities 
 
5.0 
REGISTRATION  
 
 
 
6.0 
DATA SAFETY TOXICITY COMMITTEE 
 
7.0 
DATA SAFETY AND MONITORING PLAN 
 
8.0 
RECORDS TO BE KEPT/REGULATORY CONSIDERATIONS 
8.1 
Data Reporting 
 
9.0 
REGULATORY CONSIDERATIONS 
 
10.0 
WRITTEN INFORMED CONSENT 
 
11.0 
SUBJECT DATA PROTECTION 
 
12.0  RETENTION OF RECORDS 
 
13.0  AUDITS AND INSPECTIONS 
 
14.0 
STATISTICAL CONSIDERATIONS 
 
REFERENCES 
 
  
 
 

 
CASE 6117 
Page 6 
Version date: 02/15/2019 
 
1.0 
Introduction 
 
 
1.1 
Background / Rationale 
Currently, only MRI is occasionally used to evaluate the extent of disease in some cancer 
patients, based on age, breast density and pathology subtype of the breast cancer. It is a sensitive, 
but relatively expensive, time consuming test given the additional work up (second look 
ultrasounds and biopsies) required for findings noted on the MRI. This adds to both the diagnosis 
cost and time to treat. It also helps in assessing chemotherapy response and surgical treatment 
planning.  
Our goal is to evaluate the efficacy of DBT in a similar fashion to study its role in cancer extent 
evaluation, finding additional ipsilateral and contralateral cancers, assess for multicentric and 
multifocal disease and study the role in post chemotherapy treatment planning. This is an easily 
accessible, readily available, time efficient, cost-friendly modality which may prove useful in 
providing additional information in all new breast cancer patients, since MRI is performed only 
in a select group of patients. This may prove specifically helpful in patients with non-calcified 
masses and architectural distortion. In a recent study on DBT, cancers that manifested as 
architectural distortion at diagnosis included a higher percentage of invasive lobular carcinomas 
(20%) (11). It may also lead to better mass margin assessment, tumor size and presence of 
satellite lesions. It is also a useful tool in evaluating the contralateral breast, especially since 
breast MRI is not performed in every new breast cancer patient at our institution. 
 
 
2.0  
Objectives 
 
The primary aim of the study is to study the efficacy and additional role of digital breast 
tomosynthesis (DBT) for patients with a new diagnosis of breast cancer. In the current clinical 
practice at our institution, standard 2-dimensional (2-D) mammograms (DM) are performed as 
standard of care to evaluate the extent of disease in patients with new diagnosis of breast cancer.  
DBT (colloquially referred to as a 3-dimensional mammogram) is only occasionally performed, 
at the discretion of the breast radiologist to further evaluate the findings of the 2-D mammogram. 
Recently published data shows a greater efficacy of DBT with increased cancer detection and a 
reduced call back rate for screening mammography (1-4).  Chudgar et al assessed MR extent of 
disease for cancers detected on DBT versus DM alone (5). Additional studies evaluated role of 
DBT in cancer detection and tumor size assessment in comparison to other diagnostic modalities 
(6-8), specifically Mariscotti et al assessed its role in characterizing invasive lobular cancers (9).  
Our hypothesis is that DBT may provide additional information to evaluate the extent of disease, 
including possible multifocality and multicentricity and additional findings including margin 
assessment and tumor size that would aid in staging a new breast cancer patient. This would 
impact surgical planning and improve patient outcomes. DBT is a relatively inexpensive test; in 
comparison to breast MRI which is the alternative study performed to evaluate extent of disease 
in selected new breast cancer patients.   One of the reasons that a breast radiologist may 
recommend a breast MRI for a new breast cancer patient is if the patient has dense breast tissue 
on mammography.  Performing DBT in these patients may improve the mammographic 
information about the extent of disease. Also, all the previously recently published studies were 
performed using different vendor versions of DBT other than Siemens used at our site. 
 

 
CASE 6117 
Page 7 
Version date: 02/15/2019 
 
 
2.1  
Primary Objective  
The primary objective of the study is to measure the frequency with which DBT alters the 
surgical plan to mastectomy versus lumpectomy.  Only positive findings, like an additional site 
of cancer or DCIS (findings requiring surgical intervention), will be taken into account when 
estimating the frequency of changes to surgical management. 
 
2.2 
Secondary Objective(s) 
Secondary Objectives include: 
1. To measure the frequency and nature of additional findings like atypical pathology (Atypical 
ductal/ lobular hyperplasia, papilloma, LCIS found on DBT. 
2. To identify variables on 2D (e.g. dense breasts, architectural distortions, non-calcified masses)   
that might predict which patients would benefit from DBT. 
3. To measure the proportion of patients undergoing additional work-up following the DBT, and 
the subset of these patients with benign findings (i.e. False Positives). 
 
 
3.0 
Study Design 
A prospective cohort blinded study will be performed on new breast cancer patients detected at 
our Breast centers at Main campus and Beachwood family health center between May 2017 and 
August 2019. The patients assigned a BIRADS 5 category at the time of diagnosis and all new 
diagnosed breast cancer patients, will undergo a separate 2-D plus DBT in addition to the 
standard 2-D mammogram performed at our institution at Main campus and Beachwood Family 
health center. The new breast cancer patients will be scheduled for the mammogram after 
diagnosis at the time of surgical appointment. The radiologist reviewing the tomosynthesis 
images will be separate and blinded from the radiologist who reviewed the initial 2-D 
mammogram. The following pertinent data will be collected, including number of additional 
lesions, size of the lesion, margins of the lesions, percentage of biopsy rates, cancer detection 
rate, high risk lesion detection rate, lesions resulting in excisional biopsy, lesions changed to 
mastectomy, time to treat, false positive pathology. The principal investigator and key personnel 
will periodically review all the new patients on a weekly basis. The first 150 patients acquired 
during the study time period will be evaluated to assess for their imaging findings and compared 
to the initial standard diagnostic mammogram workup. 
 
3.2 
Number of Subjects 
Approximately 150 subjects will be enrolled in this trial.  
 
 
4.0 
Inclusion Criteria 
 
Subjects must meet all of the following inclusion criteria to be eligible for enrollment:  
 
1. New diagnosis of breast cancer 
2. New diagnosis if a previous breast cancer patient with negative surgical margins 
3. Age limit: 25-85 years 
 
 
Exclusion Criteria 

 
CASE 6117 
Page 8 
Version date: 02/15/2019 
 
 
The presence of any of the following will exclude a subject from study enrollment. 
1. Male patients 
2. High risk benign lesions as the primary pathology diagnosis 
3. Patients under 25, over 85 
 
4.1 
Inclusion of Women and Minorities  
Women and members of all races and ethnic groups are eligible for this trial. 
 
5.0 
REGISTRATION 
All subjects who have been consented are to be registered in the OnCore™ Database. For those 
subjects who are consented, but not enrolled, the reason for exclusion must be recorded. 
 
All subjects will be registered through the Cleveland Clinic and will be provided a study number 
by contacting the study coordinator listed on the cover page.  
 
 
Institutional Review Board Reporting Requirements: 
• Investigative sites will report adverse events to their respective IRB according to the local 
IRB’s policies and procedures in reporting adverse events.  
 
 
SAEs and OnCore 
• All SAEs will be entered into OnCore.   
• A copy of the SAE form(s) submitted to the sponsor-investigator is also uploaded into 
Oncore. 
 
6.0  
DATA SAFETY AND TOXICITY COMMITTEE 
It is the responsibility of each site PI to ensure that ALL SAEs occurring on this trial (internal or 
external) are reported to the Case Comprehensive Cancer Center’s Data and Safety Toxicity 
Committee. This submission is simultaneous with their submission to the sponsor and/or other 
regulatory bodies  
 
The sponsor-investigator is responsible for submitting an annual report to the DSTC as per 
CCCC Data and Safety Monitoring Plan. 
  
7.0 
DATA SAFETY AND MONITORING PLAN 
This protocol will adhere to the policies of the Case Comprehensive Cancer Center Data and 
Safety Monitoring Plan in accordance with NCI guidelines.  
 
 
8.0 DATA REPORTING / REGULATORY CONSIDERATIONS  
 
Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 8.0 
(Adverse Events: List and Reporting Requirements). 
 

 
CASE 6117 
Page 9 
Version date: 02/15/2019 
 
8.1 
Data Reporting  
The OnCore™ Database will be utilized, as required by the Case Comprehensive Cancer Center, 
to provide data collection for both accrual entry and trial data management. OnCore™ is a 
Clinical Trials Management System housed on secure servers maintained at Case Western 
Reserve University. OnCore™. Access to data through OnCore™ is restricted by user accounts 
and assigned roles. Once logged into the OnCore™ system with a user ID and password, 
OnCore™ defines roles for each user which limits access to appropriate data. User information 
and password can be obtained by contacting the OnCore™ Administrator at OnCore-
registration@case.edu. 
 
OnCore™ is designed with the capability for study setup, activation, tracking, reporting, data 
monitoring and review, and eligibility verification. This study will utilize electronic Case Report 
Form completion in the OnCore™ database. A calendar of events and required forms are 
available in OnCore™. 
 
9.0 
REGULATORY CONSIDERATIONS 
The study will be conducted in compliance with ICH guidelines and with all applicable federal 
(including 21 CFR parts 56 & 50), state or local laws. 
10.0 
WRITTEN INFORMED CONSENT 
The Principal Investigator will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risks and benefits of the study as well as the 
subject’s financial responsibility. Subjects must also be notified that they are free to discontinue 
from the study at any time. The subject should be given the opportunity to ask questions and be 
allowed time to consider the information provided.  
The original, signed written Informed Consent Form must be kept with the Research Chart in 
conformance with the institution’s standard operating procedures. A copy of the signed written 
Informed Consent Form must be given to the subject.  Additionally, documentation of the 
consenting process should be located in the research chart. 
11.0 
SUBJECT DATA PROTECTION 
In accordance with the Health Information Portability and Accountability Act (HIPAA), a 
subject must sign an authorization to release medical information to the sponsor and/or allow the 
sponsor, a regulatory authority, or Institutional Review Board access to subject’s medical 
information that includes all hospital records relevant to the study, including subjects’ medical 
history.  
 
12.0  RETENTION OF RECORDS 
The Principal Investigator of The Case Comprehensive Cancer Center supervises the retention of 
all documentation of adverse events, records of study drug receipt and dispensation, and all IRB 
correspondence for as long as needed to comply with local, national and international 
regulations. No records will be destroyed until the Principal Investigator confirms destruction is 
permitted.  

 
CASE 6117 
Page 10 
Version date: 02/15/2019 
 
 
13.0  AUDITS AND INSPECTIONS  
Authorized representatives of the sponsor, a regulatory authority, an Independent Ethics 
Committee (IEC) or an Institutional Review Board (IRB) may visit the site to perform audits or 
inspections, including source data verification. The purpose of an audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analysed, and 
accurately reported according to the protocol, Good Clinical Practice (GCP), guidelines of the 
International Conference on Harmonization (ICH), and any applicable regulatory requirements.  
For multi-center studies, participating sites must inform the sponsor-investigator of pending 
audits.  
 
14.0  STATISTICAL CONSIDERATIONS 
  
 
The primary objective of the study is to measure the frequency with which DBT alters the 
surgical plan.  For this objective, the proportion of subjects with a change in surgical plan will be 
calculated and its 95% Confidence Interval (CI) constructed.  Logistic regression models will be 
used to identify variables on 2D that are predictive of patients who would benefit from DBT.  
The dependent variable in the models will be change/no change in surgical plan, and the 
independent variables will be lesion and breast characteristics.  Holm’s method will be used to 
control the family-wise type I error rate.  McNemar’s test will be used to compare the findings 
on MRI and DBT.   
 
Sample Size Justification: 
 
A 95% CI for the proportion of patients with changes in their surgical plan attributable to DBT 
can be constructed with width of +/- 8% or tighter with 150 patients.  
 
 REFERENCES 
 
1. Caumo F, Bernardi D, Ciatto S, et al. Incremental effect from integrating 3D-
mammography (tomosynthesis) with 2D-mammography: increased breast cancer 
detection evident for screening centres in a population-based trial. Breast 
2014;23(1):76–80.  
2. Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography 
alone and digital mammography plus tomosynthesis in a population-based 
screening program. Radiology 2013;267(1):47–56. 
3. Skaane P, Bandos AI, Gullien R, et al. Prospective trial comparing full-field 
digital mammography (FFDM) versus combined FFDM and tomosynthesis in a 

 
CASE 6117 
Page 11 
Version date: 02/15/2019 
 
population-based screening programme using independent double reading with 
arbitration. Eur Radiol 2013;23(8):2061–2071. 
 
4. Rafferty EA, Park JM, Philpotts LE, et al. Assessing radiologist performance 
using combined digital mammography and breast tomosynthesis compared with 
digital mammography alone: results of a multicenter, multireader trial. Radiology 
2013;266(1):104–113. 
 
5. Chudgar AV, Conant EF, Weinstein SP, et al. Assessment of disease extent on 
contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis 
versus digital mammography alone. Clin Radiol 2016; 71(9):889-95. 
 
6. Mercier J, Kwiatkowski F, Abrial C, et al. The role of tomosynthesis in breast 
cancer staging in 75 patients. Diag Interv Imaging. 2015; 96(1): 27-35. 
 
7. Mariscotti G, Houssami N, Durando M, et al. Accuracy of mammography, digital 
breast tomosynthess, ultrasound and MR imaging in preoperative assessment of 
breast cancer. Anticancer Res 2014; 34(3): 1219-25. 
 
8. Luparia A, Mariscotti G, Durando M, et al. Accuracy of tumor size assessment in 
the preoperative staging of breast cancer: comparison of digital mamography, 
tomosynthesis, ultrasound and MRI. Radiol Med 2013; 118(7): 1119-36. 
 
9. Mariscotti G, Durando M, Houssami N, et al. Digital breast tomosynthesis as an 
adjunct to digital mammography for detecting and characterising invasive lobular 
cancers: a multi-reader study.  Clin Radiol. 2016; 71(9): 889-95. 
 
10. Howlader N, Noone AM, Krapcho M, et. al. (eds). SEER Cancer Statistics 
Review, 1975–2009 (Vintage 2009 Populations), National Cancer Institute. 
Bethesda, MD, 2012. Retrieved September 7, 2012. 
 
11. Dang PA, Humphrey KL, Freer PE, Halpern EF, Saksena MA, Rafferty EA. 
Comparison of lesion detection and characterization in invasive cancers using 
breast tomosynthesis versus conventional mammography [abstr]. In: Radiological 
Society of North America Scientific Assembly and Annual Meeting Program. 
Oak Brook, Ill: Radiological Society of North America, 2013; 156.