Plain English Summary
Background and study aims
Ductal cancer in situ is a type of breast cancer in which the malignant cells are located in the milk ducts but have not yet breached and invaded to the surrounding tissues. It accounts for about 10% cases of breast cancers and is mostly detected by mammography (breast x-ray) as it does not typically form a palpable lump. As it is confined to the milk ducts, it cannot spread further to the lymph nodes or distant organs. Therefore, a biopsy (tissue sample) to assess the nodes in the axilla (armpit) is not considered mandatory. However, about 20 to 30% of cases with a diagnosis of DCIS before surgery are then found to have an invasive cancer in the surgical specimen. These patients have to undergo an axillary biopsy (sentinel node biopsy or SNB), in which the first node to which the lymph from the breast is drained (the sentinel node) is found and removed. The node is traditionally identified by injecting a radioactive substance (radioisotope) and blue dye into the breast and following the lymph vessels all the way to the sentinel node. Until now, there is no 100% accurate method to predict which patients with DCIS will be found to have invasive breast cancer after surgery. Current practice suggests that an SNB should be considered either in patients who are planned for a mastectomy (breast removal), since the SNB will not be as feasible after that, or to patients with certain aggressive symptoms, since they are most likely to have an undiagnosed invasive cancer. However, in that way, DCIS patients undergo unnecessary biopsies, resulting in side effects such as arm and shoulder pain, constricted range of motion and swelling (lymphedema), longer operative times and increased costs. Superparamagnetic Iron Oxide (SPIO) nanoparticles are a new tracer where the principle of magnetism is used to detect the sentinel node. The aim of this study is to find out whether using SPIO as a tracer avoids unnecessary SNBs in patients with DCIS.
Who can participate?
Patients with DCIS undergoing breast-conserving surgery or mastectomy
What does the study involve?
SPIO are injected at the first operation and the sentinel node is not removed. If invasive cancer is found, then the patient is taken to theatre for an SNB. If this is the case, all three methods (SPIO, isotope and blue dye) are used for the detection of the sentinel node. The aim is to see how many patients are spared unnecessary procedures and the possible impact of that in breast cancer service units. Additionally, the feasibility of sentinel node detection in the second operation is also investigated.
What are the possible benefits and risks of participating?
The benefits of taking part in the study are that an unnecessary operation in the axilla with arm and shoulder restriction, pain, numbness and swelling can be avoided. Potential drawbacks include the very rare case (<1%) of missing an invasive cancer in the specimen that might have spread to the node. However, recent data from the USA have shown that patients with DCIS who did not undergo any form of axillary surgical evaluation had comparable survival to those who underwent axillary surgery. No financial compensation will be involved for participating in the study.
Where is the study run from?
1. Uppsala University Hospital (Sweden)
2. Västmanland County Hospital (Sweden)
3. Norrlands University Hospital (Sweden)
4. Gothenburg University Hospital (Sweden)
5. Kalmar County Hospital (Sweden)
When is the study starting and how long is it expected to run for?
April 2015 to December 2021
Who is funding the study?
Uppsala University (Sweden)
Who is the main contact?
Dr Andreas Karakatsanis
andreas.karakatsanis@surgsci.uu.se
Trial website
Contact information
Type
Scientific
Primary contact
Dr Andreas Karakatsanis
ORCID ID
http://orcid.org/0000-0003-3622-3575
Contact details
Akademiska Sjukhusvägen ing 70
Uppsala
751 85
Sweden
+46 (0)765 864 826
andreas.karakatsanis@surgsci.uu.se
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SentiNot
Study information
Scientific title
The use of superparamagnetic iron oxide particles as a tracer to avoid unnecessary sentinel node biopsies in patients with a preoperative diagnosis of ductal cancer in situ
Acronym
SENTInel node biopsy in ductal cancer in situ; how to NOT do it (SENTINOT)
Study hypothesis
In Sweden, approximately 800 patients with DCIS are diagnosed each year. More than 50% of these patients undergo a sentinel node biopsy (SNB). As an in situ cancer by definition has not metastasized these SNBs are basically unnecessary. The preoperative investigation (mammography and core needle biopsy) can often signal which cases are DCIS. However, in some 15-20% of the cases, an invasive tumour component is diagnosed at the final histopathological examination of the specimen after surgery. Performing a SNB at a second operation has been considered less reliable as the lymph drainage is affected by the previous surgery and it has been considered impossible after a mastectomy since the location of the primary tumour cannot be established, and the lymphatic drainage is distorted. Also, if a SNB is performed and the patient develops a local recurrence the possibility to successfully perform a second SNB is decreased. The aim of this study, therefore, is to find a way to avoid unnecessary SNBs in patients with ductal carcinoma in situ (DCIS).
Ethics approval
Uppsala University Ethics Committee, 13/04/2015, ref: 2014:073
Study design
Prospective single-arm observation cohort
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Ductal Cancer in Situ (DCIS)
Intervention
Sienna+ (2ml + NaCl 3ml) will be injected in association with the primary breast surgery on patients with a preoperative diagnosis of DCIS. The Sienna+ is injected close to the tumour, subcutaneously. The sentinel node (SN) is uploaded with Sienna+ but is not removed. The counts by SentiMag is measured transcutanously at the end of the procedure.
The patient is scheduled for a visit to the breast unit within 2 weeks after surgery. If there is an invasive tumour component on the final histopathological examination, a sentinel node biopsy (SNB) will be performed at a second operation within 1-2 weeks. A preoperative injection of radioisotope will be made to maximize the chance to detect the SN.
This SNB will start with a registration of the magnetic- and isotope signal in the axilla, and the incision will be placed in relation to the signal. If no activity is measured, an injection of 1 ml Patent Blue Dye will be made in the area of the breast where the tumour was located. After a sufficient waiting time, 5-10 minutes, a small incision will be made in the lower part of the axilla, and careful dissection will be made to identify lymphatic vessels and lymph nodes. After a mastectomy, the lateral part of the earlier incision is used. If no SN is found, an axillary clearance or sampling will follow, according to the surgeon's decision. The SN will be sent for frozen section in order to avoid a third operation if SN metastases are present.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measures
Number of SNB procedures spared, defined as those cases of patients with a definite postoperative diagnosis of pure DCIS in whom no SNB will be performed
Secondary outcome measures
SNB detection rate in a second operation, defined as the number of successful SNBs for each patient and for each method (SPIO, isotope and blue dye) divided by the total amount of SNBs performed
Overall trial start date
01/04/2015
Overall trial end date
30/08/2021
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients with a preoperative diagnosis of DCIS grade 3 any size or, DCIS grade 2 larger than 20 mm on mammography and planned for breast conserving surgery (BCS)
2. Patients with a preoperative diagnosis of DCIS, any grade and any size, planned for mastectomy
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. Patients undergoing a direct reconstruction with autologous tissue
2. Intolerance/hypersensitivity to iron or dextran compounds or Sienna+
3. Patients with an iron overload disease
4. Patients with pacemakers or other implantable devices in the chest-wall, or prosthesis in the shoulder
5. Patient deprived of liberty or under guardianship
6. Pregnant or lactating patients
Recruitment start date
01/05/2015
Recruitment end date
30/12/2020
Locations
Countries of recruitment
Sweden
Trial participating centre
Uppsala University Hospital
Uppsala
751 85
Sweden
Trial participating centre
Västmanland County Hospital
721 89
Sweden
Trial participating centre
Norrlands University Hospital
Umeå
901 85
Sweden
Trial participating centre
Gothenburg University Hospital
413 45
Sweden
Trial participating centre
Kalmar County Hospital
391 85
Sweden
Sponsor information
Organisation
Uppsala University
Sponsor details
Box 256
Uppsala
751 05
Sweden
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
Uppsala Universitet
Alternative name(s)
Uppsala University
Funding Body Type
private sector organisation
Funding Body Subtype
academic
Location
Sweden
Results and Publications
Publication and dissemination plan
A pre-planned interim analysis is planned until 30/06/2018.
For full trial results, planned publication in a high-impact peer reviewed journal is intended approximately on 30/04/2022.
IPD sharing statement: The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
30/04/2022
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary