Trial Title:
Preoperative Magnetic Resonance Imaging to Obtain Adequate Resection Margins in Breast Conserving Surgery, (PRIMAR) Trial
NCT ID:
NCT05825768
Condition:
Breast Cancer
Conditions: Keywords:
Resection Margins
repeat surgery
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomized, open-label, double-center trial including female participants with early
breast cancer planned for breast conserving surgery randomised 1:1 in a Magnetic
Resonance Imaging, MRI-group (preoperative MRI, ultrasound and mammography) and a control
group (preoperative ultrasound and mammography).
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Device
Intervention name:
Breast MRI
Description:
Breast Magnetic Resonance Imaging prior to breast conserving surgery with and without
intravenous contrast agent.
Arm group label:
MRI-group
Intervention type:
Diagnostic Test
Intervention name:
standard breast imaging
Description:
The control group that receives standard preoperative imaging only (breast ultrasound and
mammography)
Arm group label:
Control group
Arm group label:
MRI-group
Summary:
The goal of this randomised study is to investigate if a supplementary preoperative
breast Magnetic Resonance Imaging (MRI) improves the assessment of breast cancer and can
help surgical planning such that sufficient resection margins can be obtained during
breast conserving surgery.
The main questions are:
1. Is preoperative breast MRI in addition to the currently used standard imaging
methods ultrasound and mammography more accurate to detect Ductal Carcinoma in Situ
and the invasive breast tumor compared to standard methods only?
2. Does preoperative breast MRI reduce the number of involved histological margins
after breast conserving surgery in the MRI-group versus the control group?
Detailed description:
Magnetic Resonance Imaging (MRI) of the breast preoperatively is a well-known imaging
method in primary breast cancer and is only used as a complement to the standard imaging
methods in complex cases, lobular cancer, patients with large tumors that need
preoperative neoadjuvant therapy or for patients with dense breast tissue where the tumor
is difficult to detect with the standard imaging methods. The MRI is not used as a
standard diagnostic method, because of its lower specificity that may result in a higher
false-positivity rate.
The advantage of the MRI with use of intravenously contrast agent (also called dynamic
enhanced MRI), is its ability to simultaneously assess the tumor morphology and
semiquantitative enhancement kinetics that evaluate the newly formed vessels as a
tumor-specific feature. A fast-initial enhancement and wash-out (type III) is typically
seen in malignancies, due to increased vascular permeability, density, and interstitial
fluid. Furthermore, the breast MRI can identify preinvasive malignant lesions such as
Ductal Carcinoma in Situ (DCIS) in the breast with a much higher sensitivity than
mammography and most commonly manifests as non-mass-enhanced lesion on an MRI with
intravenous contrast agent. Less frequently the DCIS manifests as a mass or a focus on
MRI and is usually not visible on non-contrast enhanced MRI, because it is masked by the
normal breast parenchyma. Few larger randomized trials have investigated the efficacy of
preoperative MRI in breast cancer and its effect on involved histological margins after
breast conserving surgery that lead to repeat surgery. Controversy still exists whether
preoperative MRI of the breast can reduce the number of repeat surgery in breast cancer.
We aim to investigate in this randomised study if a supplementary breast MRI
preoperatively with an optimised MRI scan protocol can help surgical planning to detect
the DCIS and invasive cancer such that tumor free resection margins can be obtained
during breast conserving surgery (BCS) and the patients can avoid repeat surgery.
Methods:
The study will be performed as a clinical, open-label, prospective and randomized study.
We will include 440 breast cancer patients, randomized to either MRI of the breast prior
to BCS together with the standard methods: Ultrasound and mammography (220) or to
standard methods only (220) at two different breast centers, Aarhus University Hospital
(AUH) and Viborg Regional Hospital (VRH).
The MRI of the breast: Will be performed with a protocol with intravenous contrast agent,
Dotarem on a 3 Tesla Siemens MRI at the Department of Radiology at AUH and a 1.5 Tesla
Siemens MRI System at VRH, with breast adaptive coils and diffusions sequences. The MRI
of the breast will be performed soon after the patient is included in this study and will
not delay surgery. The MRI protocol consists of T2- and T1-weighted spin-echo sequences
in the axial plane, a T2-weighted sequence, dynamic contrast enhanced subtracted series
with intravenous contrast agent Dotarem and diffusions-sequences, with breast adaptive
coils at each institution. The MRI images of the breast from VRH for each patient will be
sent to AUH, where the images will be interpreted by an experienced breast radiologist,
using the same picture archiving and communication system from Siemens Healthcare. The
tumor and DCIS will be measured, localized anatomically and presented for the breast
surgeon at each institution at Multi-Disciplinary-Team conferences at each institution.
The size of the invasive tumor and the DCIS in the breast will be recorded and compared
to the corresponding size on the standard methods with mammography and ultrasound.
Ultrasound and mammography of the breast: Are routine methods at both institutions that
are used as part of the triple diagnosis of breast cancer (palpation of the breast,
ultrasound and mammography of the breast and ultrasound-guided core biopsy of the tumor).
Ultrasound and mammography are performed and interpreted at both institutions by
dedicated and specialized breast radiologists.
Final histopathology: The final microscopical assessment of the margins are the reference
method for the final status of the margins and will be performed by experienced breast
pathologists. According to the Danish Health Board´s recommendations, a final pathology
report should be available after 7 workdays.
Statistical Analysis:
Power calculation: The number of repeat surgery for positive margins after BCS is in
average 20%. A sample size of at least 219 patients was calculated as necessary to detect
a reduction from 20% in the non-MRI group to 10% in the MRI-group with a statistical
power of 80% and a 5% level of significance. We expect that few patients may drop-out for
different reasons, and we estimated that a total number of 440 patients are enough to be
included. Chi-square test will be used to compare outcomes with categorical variables.
Regression analysis will be used for adjusted analysis. A p-value of less than 0.05 will
be considered statistically significant.
Safety:
Allergic reactions to contrast intravenous contrast Dotarem with Gadolinium that we plan
to use are very rare, approximately 0,1 %, where most are mild with skin rash.
Should an allergic reaction happen during contrast administration to the study patient,
the radiologist will examine the patient and initiate medical treatment according to the
severity of the adverse event and according to local instruction at each department.
During the first consultation with the surgeon, the patient will be asked about previous
allergic reactions towards contrast agents. If the patient has previously had severe
allergic reaction towards the MRI contrast agent Dotarem, the patient will not be
included in the study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Newly diagnosed women with biopsy-verified invasive breast cancer
- Age > 18 year
- Eligible for Breast Conserving Surgery (BCS) based on preoperative ultrasound and
mammography
- Cooperative to receive an Magnetic Resonance Imaging (MRI)-examination
Exclusion Criteria:
- Planned mastectomy
- Included patients where the planned BCS changes to mastectomy based on preoperative
MRI
- Patients where a preoperative MRI is requiered (patients treated with neoadjuvant
therapy and complex cases where a preoperative MRI is needed)
- Previous surgery for pre-malignant or malignant lesions in the breast
- Pregnancy and lactation
- Male breast cancer
- Contraindications for an MRI-examination (pacemaker, severe kidney insufficiency
with glomerular filtration rate < 30 mL/min, and MRI incompatible implants or
devices, claustrophobia, disability that prevents an MRI-examination in a prone
position, allergy towards Dotarem (intravenous contrast agent for MRI)
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Department of Plastic- and Breast Surgery, Aarhus University Hospital
Address:
City:
Aarhus
Zip:
8200
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Peer Christiansen
Phone:
+45 23708191
Email:
peerchri@rm.dk
Contact backup:
Last name:
Irina P Manhoobi
Phone:
+45 29465313
Email:
irinpali@rm.dk
Facility:
Name:
Department of Surgery, Viborg Regional Hospital
Address:
City:
Viborg
Zip:
8800
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Inge Andersen, MD, PhD
Phone:
+45 78446362
Email:
ingander@rm.dk
Contact backup:
Last name:
Irina Manhoobi, MD
Phone:
+45 29465313
Email:
irinpali@rm.dk
Start date:
February 1, 2021
Completion date:
August 31, 2026
Lead sponsor:
Agency:
Aarhus University Hospital
Agency class:
Other
Source:
Aarhus University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05825768
