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Trial registered on ANZCTR


Registration number
ACTRN12616001696482
Ethics application status
Approved
Date submitted
1/12/2016
Date registered
9/12/2016
Date last updated
21/11/2018
Date data sharing statement initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Can contrast enhanced spectral mammography (CESM) play a clinically useful role in the pre-operative assessment of women with Ductal Carcinoma in Situ (DCIS), the ‘CESM D’ study
Scientific title
Can contrast enhanced spectral mammography (CESM) play a clinically useful role in the pre-operative assessment of women with Ductal Carcinoma in Situ (DCIS), the ‘CESM D’ study
Secondary ID [1] 290319 0
None
Universal Trial Number (UTN)
U1111-1190-5385
Trial acronym
‘CESM D’ study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ductal Carcinoma in Situ 300584 0
Condition category
Condition code
Cancer 300435 300435 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women with a biopsy-confirmed diagnosis of ductal carcinoma in situ (DCIS) will be identified in the Breast Clinic at Perth Royal Hospital.
Women who give written, informed consent and who meet the eligibility criteria for the study will be given an appointment for Contrast Enhanced Spectral Mammography (CESM).
For the CESM study, an intravenous cannula will be inserted by a trained staff member and an injection of non-ionic iodinated contrast (1.5mg/kg delivering 350mg/ml up to a maximum of 125ml) will be given using a power injector at a rate of 3ml/s. Two minutes later, standard mammographic views (CC and MLO of both breasts) will be performed using dual-energy exposures. Additional views may be obtained if necessary.

The CESM study will be independently read by two radiologists on standardised case report forms according to modified Breast Imaging Reporting and Data System (BI-RADS) MR descriptors.
If the CESM does not show any significant additional findings that would change the recommended treatment plan, no further investigations will be needed prior to the routine surgical appointment.
Further assessment will be performed if there are additional findings based on the CESM which could change recommended management if confirmed to be malignant and may include targeted ultrasound (US), additional mammographic views and breast MRI. If there are additional findings that cannot be downgraded to a NBCC 2 or below (i.e. benign) on further work-up and if determination of the underlying pathology will change treatment, core needle biopsy or preoperative image guided localisation for open biopsy will be performed after multidisciplinary discussion.

In instances where biopsy is not possible or biopsy result is benign or inconclusive, follow-up breast imaging at six to twelve months post treatment using the most appropriate modality will be the default recommendation. If all further imaging is negative (US, mammogram and CEMRI), surgical planning will proceed as per findings on standard of care imaging with routine annual follow-up mammography. Wherever possible all additional imaging prompted by the CESM study will be performed within the usual time frame between diagnosis and the surgical planning appointment for patients seen in the public system (2 weeks).

Surgeons will be asked to complete a questionnaire documenting if / how the findings on CESM influenced the surgical plan recommended to the participant.

As per standard of care for patients who have had breast conserving surgery, all participants will have a routine cancer follow-up mammogram 12 months following their treatment.
Intervention code [1] 296130 0
Diagnosis / Prognosis
Comparator / control treatment
All patients will have mammography +/- ultrasound prior to the CESM study. We intend to compare the maximum size of lesion on all imaging techniques with the final pathology, and between imaging techniques. Thus patients will provide their own 'control'. As this is a pilot study is is unfortunately not feasible to have a separate control group
Control group
Active

Outcomes
Primary outcome [1] 299875 0
Accuracy of CESM for the measurement of index lesion size for CESM assessed by comparison with standard imaging (mammography +/- ultrasound) and final histopathology from surgery.
Timepoint [1] 299875 0
Upon histopathological assessment of surgical specimen (usually within two weeks of CESM).
Primary outcome [2] 300418 0
The presence of additional lesions detected on CESM assessed. These will be classified as follows:
* True positive: lesions graded NBCC 3, 4 or 5 on CESM confirmed to be malignant on pathology.
* False positive: lesions graded NBCC 3, 4 or 5 on CESM confirmed to be benign on pathology negative or stable on follow-up imaging one year post treatment
* True negative: lesions graded NBCC 1 or 2 on CESM confirmed benign on pathology or stable on follow-up imaging one year post treatment.
* False negative: lesions not reported or those graded as NBCC 1 or 2 on CESM confirmed malignant on pathology or showing progression on follow-up imaging

Timepoint [2] 300418 0
For the majority of individual patients this will following image guided biopsy of the additional lesion (usually within two weeks of CESM). There may be a few cases were the additional lesion cannot be biopsied, these will be followed-up with imaging at one year.
Primary outcome [3] 300419 0
To gauge whether the addition of CESM alters the recommended management plan. To do this the surgeon will complete a case report form at the time of the participant’s treatment planning appointment. Changes will be recorded as: nil, wider local excision, wide local excision changed to mastectomy, unilateral surgery changed to bilateral surgery, sentinel node biopsy (CESM-directed extra percutaneous biopsies showed unsuspected invasive disease).
Timepoint [3] 300419 0
Following surgery (usually within two weeks of CESM)
Secondary outcome [1] 328363 0
Intensity of enhancement will be graded by radiologists as nil, mild, moderate and marked. This will be correlated with the histological features of the DCIS (including grade and presence of necrosis).
Timepoint [1] 328363 0
One year from start of trial
Secondary outcome [2] 328364 0
Cost effectiveness of the addition of CESM to standard imaging: costs will be evaluated using prospective data collection for each participant. The analysis will include the costs associated with the intervention (CESM and additional biopsies) and outcomes (extent/ size of lesions and changes in the surgical plan) using a health provider perspective.

The costs and outcomes associated with delivering the intervention will be compared using cost-effectiveness analysis. Since change in management is mediated by change in the extent / size of the DCIS lesion identified via the addition of CESM to conventional imaging a standard cost effectiveness evaluation will be undertaken using decision tree analysis. The tree begins with a decision node depicting treatment options (the addition of CESM versus conventional imaging alone) for participants. Each option becomes a main branch off the box, which further divides into smaller branches at a ‘chance node’ as certain pre-defined events (outcomes) occur. In our study the outcome event is change in surgical management as the effectiveness payoff.

Decision trees illustrate both the probability of each outcome and the costs associated with the resultant outcome event. The likelihood of each consequence is expressed as a probability of occurrence and cost calculated from trial data. Thus, it will be possible to calculate expected cost and expected outcome of each option under evaluation. For a given option, expected cost is the sum of costs of each outcome weighted by probability of that outcome.
Timepoint [2] 328364 0
One year from start of trial

Eligibility
Key inclusion criteria
a. Able to give written informed consent
b. Women with one or more pure ductal carcinoma in situ (DCIS) lesion(s) on core biopsy
c. Women who are over the ages of 18 at diagnosis
d. Women undergoing assessment at Royal Perth Hospital, WA
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
a. Inability to give written informed consent (women whose English comprehension is such that they are considered unable to give informed consent will be excluded)
b. Evidence of invasive disease within the subject focus of DCIS
c. Women who decline or are unfit to have breast surgery
d. Women who are pregnant or lactating.
e. Contraindications for CESM including
i. Previous reaction to contrast media or allergic reaction requiring medical attention
ii. Known renal disease (including renal transplant)
iii. Diabetes Mellitus (including any patient taking metformin)
iv. Poorly controlled asthma
v. Known or suspected thyrotoxicosis
vi. Patients who are to undergo diagnostic or therapeutic procedures involving radioisotope scanning of the thyroid within 8 weeks of CESM.
vii. Known Myasthenia graves
viii. Previous administration of IV contrast within 24hours
f. Presence of breast implants
g. Limited mobility such that the CESM study cannot be completed within 10 minutes of contrast injection

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
This trial is a study of agreement for the measurement of the lesion size for CESM versus standard mammography +/- ultrasound and final histopathology. The agreement between these measurements will be assessed using Bland-Altman plots and calculating the mean difference in diameter between these measurements, including their 95% limits of agreements. Correlation between maximum tumour diameter based on CESM and histopathology, and standard imaging and histopathology will be evaluated using scatterplots and Pearson’s correlation coefficient.

In a recent local audit of DCIS cases the mean lesion size was 46mm and standard error 3.3285. Our sample size of 60 participants will give us 95% power to accurately estimate limits of agreement to within 1.48mm, which is within the limits of variability related to the precision of lesion measurement techniques on the picture archiving and communication system

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/01/2017
Actual
23/05/2017
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
14/01/2019
Actual
Sample size
Target
60
Accrual to date
52
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 7062 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 14790 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 294702 0
Charities/Societies/Foundations
Name [1] 294702 0
The Royal Australian and New Zealand College of Radiologists
Country [1] 294702 0
Australia
Funding source category [2] 294703 0
Charities/Societies/Foundations
Name [2] 294703 0
The Royal College of Radiologists
Country [2] 294703 0
United Kingdom
Primary sponsor type
Individual
Name
Clin. Assoc. Prof. Donna Taylor
Address
Department of Radiology
Royal Perth Hospital
197 Wellington St,
Perth
WA 6000
Country
Australia
Secondary sponsor category [1] 293547 0
None
Name [1] 293547 0
Address [1] 293547 0
Country [1] 293547 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296456 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [1] 296456 0
Ethics committee country [1] 296456 0
Australia
Date submitted for ethics approval [1] 296456 0
Approval date [1] 296456 0
08/09/2016
Ethics approval number [1] 296456 0
2016-156

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69650 0
A/Prof Donna Taylor
Address 69650 0
Radiology Department
Royal Perth Hospital
197 Wellington Street
Perth City
Perth
WA 6000
Country 69650 0
Australia
Phone 69650 0
+61 89 2242125
Fax 69650 0
+61 89 2243764
Email 69650 0
donna.taylor@health.wa.gov.au
Contact person for public queries
Name 69651 0
Donna Taylor
Address 69651 0
Radiology Department
Royal Perth Hospital
197 Wellington Street
Perth City
Perth
WA 6000
Country 69651 0
Australia
Phone 69651 0
+61 89 2242125
Fax 69651 0
+61 89 2243764
Email 69651 0
donna.taylor@health.wa.gov.au
Contact person for scientific queries
Name 69652 0
Donna Taylor
Address 69652 0
Radiology Department
Royal Perth Hospital
197 Wellington Street
Perth City
Perth
WA 6000
Country 69652 0
Australia
Phone 69652 0
+61 89 2242125
Fax 69652 0
+61 89 2243764
Email 69652 0
donna.taylor@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Yet to be decided by Principal investigator


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.