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Trial registered on ANZCTR


Registration number
ACTRN12616000533493
Ethics application status
Approved
Date submitted
10/03/2016
Date registered
26/04/2016
Date last updated
2/03/2020
Date data sharing statement initially provided
2/03/2020
Date results information initially provided
2/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Is contrast enhanced spectral mammography (CESM) useful in the investigation of possible abnormalities found on screening mammograms in women with dense breast tissue and does it add useful and important information over and above current standard imaging tests?
Scientific title
Efficacy of contrast enhanced spectral mammography versus standard of care imaging tests (tomosynthesis and ultrasound) in women with mammographically dense breast tissue recalled for investigation of abnormalities detected on routine screening mammograms.
Secondary ID [1] 287959 0
None
Universal Trial Number (UTN)
U1111-1176-8037
Trial acronym
CESM T Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 297721 0
Condition category
Condition code
Cancer 297906 297906 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
On arrival the participants have a cannula inserted into a vein and an injection of iodine based contrast (dose of which is dependent on participants' weight. This is usually approximately 100mls of Omnipaque 350 mgI/ml). Following this (approximately 3-5 minutes later) the participant is asked to stand still in front of the x-ray machine whilst images are taken. The entire study takes approximately 10 minutes from the time of the injection. A log of the contrast administered to each participant will be kept.
Contrast Enhanced Spectral Mammography is performed using special equipment that produces high and low energy XRays and is able to logarithmically subtract these images to produce a processed image that shows areas of contrast enhancement within the breast tissue.
Intervention code [1] 293977 0
Diagnosis / Prognosis
Comparator / control treatment
The standard of care is tomosynthesis of the breast and also breast ultrasound.
The tomosynthesis scan is a type of mammogram in which the XRay tube moves in an arc over the breast whilst a series of images are obtained. This produces images that look like "slices" through the tissue, removing overlapping structrues to show possible underlying abnormalities more clearly. Usually two views are obtained of the breast in which the possible abnormality was noted on the screening mammogram.
The breast is compressed for the tomosynthesis scan just as it is for a standard mammogram. Each scan takes only a few seconds more than a standard mammogram. A tomosynthesis study of one breast usually involves two views and takes approximately four minutes (including the time taken by the radiographer to position the breast) to complete.
During this study, the tomosythesis scan and the contrast enhanced scans are performed in quick succession whilst the breast is compressed for each mammographic image, This combined examination takes approximately 90 seconds per view, with two views per breast being obtained as standard.
Breast ultrasound involves the participant lying on her back, Warm ultrasound gel is placed in the breast surface and a hand held probe is gently run across the skin. Sound waves are used to produce images of the breast tissue. The ultrasound scan of both breast takes approximately 15-20 minutes to perform and does not involve the use of any radiation.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297426 0
Sensitivity of CESM in comparison to tomosynthesis and/or ultrasound.
The assessment of sensitivity is defined as the proportion of index lesions that are malignant on core biopsy or excisional histology that were graded as Tabar score 3, 4, or 5 by the assessment radiologists based on the assessment modality.
Timepoint [1] 297426 0
First Assessment visit
Primary outcome [2] 297427 0
Specificity of CESM in comparison to tomosynthesis and/or ultrasound.
The assessment of specificity is defined as the proportion of index lesions that are not malignant on pathology that are graded as Tabar score 1 or 2 based on the assessment modality.
Timepoint [2] 297427 0
First Assessment Visit
Primary outcome [3] 297999 0
Number of lesions for which biopsy is felt to be indicated.
This is assessed by comparing the radiologists grading of each lesion based on each modality.
Timepoint [3] 297999 0
First Assessment Visit
Secondary outcome [1] 321010 0
Radiologists' degree of confidence with which lesions are classified as benign or malignant.
The degree of confidence of the radiologist as to the likelihood of the lesion being benign or malignant (Likert 1-5 scale) will also be recorded after each additional investigation.
Timepoint [1] 321010 0
First Assessment Visit
Secondary outcome [2] 321663 0
Requirement for ultrasound.
This is assessed by reviewing each modality to see whether ultrasound detected any additional lesions not shown on CESM and also whether ultrasound improved accuracy of lesion etiology.
Timepoint [2] 321663 0
Within a few days of the initial assessment
Secondary outcome [3] 322873 0
Feasibility of performing CESM during a busy clinic.
This will be assessed by monitoring delays or disruptions in the usual clinic work flow.
Timepoint [3] 322873 0
At the time of first assessment

Eligibility
Key inclusion criteria
1. Written informed consent
2. Women between the ages of 18 and 65 years with dense breast tissue on their mammograms who have been recalled for further assessment of a non calcified lesion detected on screening mammography
3. Women with one or more non-calcified lesions detected on mammography where tomosynthesis is indicated as part of the assessment investigations.
4. Presence of dense breasts (heterogeneously or extremely dense background parenchymal pattern) on mammography
Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Lesions for which a standard work-up procedure would not include Tomosynthesis
2. Presence of breast prostheses (CESM does not give good images in presence of prostheses)
3. Poor mobility (Participants must be able to stand and be positioned adequately)
4. Pregnancy or lactation
5. Previous reaction to IV iodinated or gadolinium contrast
6. History of multiple allergies requiring medical treatment
7. History of asthma
8. Women unable to give informed consent due to intellectual impairment
9. Women whose primary language is not English whose level of comprehension is believed to be insufficient for them to be able to give written informed consent without a Health Department approved interpreter
10. Poor mobility / physical limitations that would make CESM study impractical to perform
11. Presence of risk factors for or a known history of impaired renal function (as identified using the IV contrast administration guidelines)
12. Age over 65
13. Diabetic
14. Thyroid disease: Untreated hyperthyroidism or presence of a known hyperfunctioning thyroid nodule. Patients scheduled to undergo diagnostic or therapeutic procedures involving radioisotope scanning of the thyroid (including thyroid cancer treatment) (radioisotope uptake will be prevented for 8 weeks following iodinated contrast administration).
15. History of Myasthenia Gravis
16. Women who are taking Beta Blocking medication
17. Women who are being treated with Interleukin-2

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/06/2016
Actual
23/11/2016
Date of last participant enrolment
Anticipated
1/08/2017
Actual
10/07/2017
Date of last data collection
Anticipated
29/06/2018
Actual
28/02/2020
Sample size
Target
60
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 5306 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 12771 0
6001 - Perth

Funding & Sponsors
Funding source category [1] 292933 0
Charities/Societies/Foundations
Name [1] 292933 0
Breast Cancer Research Center - WA
Country [1] 292933 0
Australia
Funding source category [2] 293084 0
Hospital
Name [2] 293084 0
Medical Research Foundation of Royal Perth Hospital
Country [2] 293084 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
197 Wellington Street,
Perth
WA
6000
Country
Australia
Secondary sponsor category [1] 291869 0
None
Name [1] 291869 0
None
Address [1] 291869 0
None
Country [1] 291869 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294592 0
Royal Perth Hospital Human Research Ethics Committee (EC00270)
Ethics committee address [1] 294592 0
Southern Integrated Research Organisation (SIRO),
Locked Bag 100,
Palmyra DC,
WA,
6961
Ethics committee country [1] 294592 0
Australia
Date submitted for ethics approval [1] 294592 0
24/02/2016
Approval date [1] 294592 0
06/05/2016
Ethics approval number [1] 294592 0

Summary
Brief summary
The primary purpose of this trial is to investigate the feasibility and efficacy of performing contrast enhanced spectral mammography (CESM) in comparison with the standard of care tests (which are breast tomosynthesis and ultrasound) for the detection of breast cancer in women with dense breast tissue.
Who is it for?
You may be eligible to participate in this study if you are aged 18 to 65, have dense breast tissue and have been recalled for further investigation of least one non-calcified finding on a screening mammogram.
Study details:
As part of standard care investigations, all participants enrolled in this trial will undergo tomosynthesis of the breast in which a possible abnormality has been found and an ultrasound scan of both breasts. The tomosynthesis study is a type of mammogram that is able to show the breast tissue slices, As part of this trial, a contrast enhanced spectral mammogram is being tested. This involves the injection of a dye into a vein, followed by two mammogram pictures of each breast taken 2-4 minutes later. The specialised equipment used for the CESM study is able to take mammograms at two different energy levels as well as performing the normal tomosynthesis study.
This CESM study is taken at the same time as the tomosynthesis scan and the combined tomosynthesis and CESM study will take about 12 minutes from the start of the injection to completion of the pictures.
During this study, the injection will be given first with the participant seated. Two to four minutes later the participant is asked to stand and mammograms of both breasts will be taken with the breasts gently compressed. The tomosynthesis mammograms are taken first, immediately followed by the contrast enhanced mammogram. The tomosynthesis and CESM scans are both taken during the same episode of breast compression ie each breast is only compressed once for each of the views that is taken. Having the CESM scan will mean the breast is compressed for approximately one extra minute longer per view than for a tomosythesis only scan.
Researchers will compare the results of the CESM scans to the results from the tomosynthesis and ultrasound scans. Based on all results available, the physician will then make a decision as to whether any further tests, such as a needle biopsy are needed. The treating doctor will be asked to rate their level of confidence in the diagnosis made, and researchers will follow-up to assess whether performing the CESM scan was able to reduce the need for further tests such as needle biopsy and ultrasound. It is hoped that the findings from this trial will provide information on whether CESM may be a useful and feasible tool to aid in the diagnosis of breast cancer in women with dense breasts and help prevent unnecessary extra tests.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61714 0
A/Prof Donna Taylor
Address 61714 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
GPO Box X2213,
Perth, WA, 6001
Country 61714 0
Australia
Phone 61714 0
+61 8 9224 2125
Fax 61714 0
Email 61714 0
donna.taylor@health.wa.gov.au
Contact person for public queries
Name 61715 0
Donna Taylor
Address 61715 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
GPO Box X2213,
Perth, WA, 6001
Country 61715 0
Australia
Phone 61715 0
+61 8 9224 2125
Fax 61715 0
Email 61715 0
donna.taylor@health.wa.gov.au
Contact person for scientific queries
Name 61716 0
Donna Taylor
Address 61716 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
GPO Box X2213,
Perth, WA, 6001
Country 61716 0
Australia
Phone 61716 0
+61 8 9224 2125
Fax 61716 0
Email 61716 0
donna.taylor@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Discussions with investigators ongoing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.