Use of Magtrace Bracketing for Excision of Lesion and Sentinel Lymph Node Localization in Breast Conserving Surgery for Breast Cancer (MagBracket)
Use of Super Paramagnetic Iron Oxide (Magtrace) Bracketing for Excision of Lesion and Sentinel Lymph Node Localization in Breast Conserving Surgery for Breast Cancer - The MagBracket Study.
Breast cancer is the commonest cancer affecting women worldwide. Early breast cancer is treated surgically with wide local excision of tumor with axillary staging operations like sentinel node biopsy. Surgical adjuncts used in identifying and localizing the area for excision include metallic wire, radioactive or magnetic seeds and radiofrequency reflectors. These are placed in the lesion under image guidance by the breast radiologists, either on the day of surgery (wires) or prior (seeds). Bracketing localization is performed in case of multiple lesions or wide spread calcifications to aid the surgeons in performing wide local excision of all involved areas. This means placing multiple devices around the area of excision for accurate triangulation, which increase the costs significantly.
Localization agents like radionucleotide labelled albumin, super paramagnetic iron oxide (SPIO) and colored dyes like methylene blue, isosulphane blue and indocyanine green are injected in the breast for identification of sentinel lymph nodes in the axilla.
More recent studies have demonstrated successful use of SPIO in localization of small impalpable breast cancer lesions. This also raises the prospect of using SPIO for the dual purpose of lesion localization / bracketing and sentinel node biopsy. This study was designed to test this principle in patients requiring bracketing.
This is a prospective proof-of-concept pilot study to evaluate the feasibility of SPIO (Magtrace®) as a single-agent solution for bracketing the excision area and localizing the sentinel lymph node for breast-conserving surgery. Patients with breast cancer requiring bracketing and sentinel node biopsy will be identified through multidisciplinary breast tumor board and invited to take part in the study. All patients who consent to participate will receive an injection of Magtrace® for bracketing (0.5ml each at four points around the excision area) one day before surgery under ultrasound guidance. Primary outcome will be successful localization of the Magtrace® signal in breast for bracketing and in the sentinel node, using a magnetic probe on the day of surgery. Clinical outcomes, complications and cost analyses will be performed as secondary outcomes. We anticipate a sample size of 35 patients to be recruited for the study.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Early-stage breast cancer is commonly managed with breast-conserving surgery (BCS) and sentinel lymph node biopsy (SLNB), aiming to minimize surgical morbidity while achieving optimal cosmetic results. Accurate preoperative or intraoperative localization of both the breast lesion and the sentinel lymph node is essential for complete tumor excision and accurate nodal staging.
Bracketed Localization of Breast Lesions Among the available localization methods, bracketed localization is used to delineate the boundaries of wide local excision in cases of extensive suspicious changes, calcifications, or multiple lesions related to invasive or in situ breast cancer. Historically, wire-guided localization (WGL) has been the standard for bracketed lesion localization; however, it can pose challenges such as wire displacement, patient discomfort, and variable success rates . In an effort to overcome these drawbacks, alternative approaches-such as radioactive seed localization and magnetic seed localization-have shown promising results.
Sentinel Lymph Node Localization and Dual-Tracer Approaches Sentinel lymph node biopsy remains a cornerstone in breast cancer staging and typically involves injecting a radioisotope and/or blue dye. Recently, superparamagnetic iron oxide (SPIO) tracers, such as Magtrace®, have emerged as an effective alternative, eliminating the need for handling radioactive materials. The Magnetic Sentinel Node and Occult Lesion Localization (MagSNOLL) framework has demonstrated the feasibility of leveraging magnetic tracers for both lesion and lymph node localization.
Although dual-tracer methods, where one agent targets the lesion and another identifies the sentinel lymph node, are well-established, using a single agent to perform both tasks has been less common in routine clinical practice. In many protocols that incorporate SPIO for sentinel node detection, separate localization tools (e.g., wires or radioactive seeds) are still employed for the primary lesion.
Rationale - Magtrace as a Dual Modality Magtrace® (SPIO) has consistently demonstrated safety and accuracy for sentinel lymph node localization. It is proposed that Magtrace® can also be utilized for bracketing the primary tumor, referred to here as bracketing Magnetic Tracer Localization (bMTL). By consolidating both bracketing and sentinel lymph node localization into a single modality, it may be possible to streamline the surgical process, reduce the number of procedures, and potentially improve patient experiences and outcomes.
Objectives
This study explores the feasibility and efficacy of Magtrace® as a dual agent for bracketing breast lesions and localizing the sentinel lymph node in BCS. The objectives include:
- Assessing Feasibility: Determining whether bracketed Magtrace® Localization can be reliably performed in a clinical setting.
- Non-inferiority to current localization methods for bracketing.
- Streamlining Surgical Workflow: Investigating whether employing a single-agent method reduces operative time, logistical complexity, and patient discomfort.
Design The study is designed as a prospective proof of concept pilot cohort study.
Recruitment:
Patients will be Identified form breast multidisciplinary tumor board for Inclusion In the study. All patients fulfilling the Inclusion criteria will be invited to take part. Informed consent will be obtained for all patients who agree to take part in the study.
Intervention and assessment:
Lesion localization procedure will be performed one day before or on the day of surgery. Patients included in the study will have localization of primary cancer / cancers with Magseed® and bracketing with Magtrace® under ultrasound / Mammographic guidance as indicated, in accordance with the local treatment protocol. The Consultant Radiologist using Magtrace® will perform bracketing under image guidance. 0.5ml of Magtrace® will be injected into the breast parenchyma superior, inferior, medial and lateral to the area planned for excision.
The operating surgeon will review patient on the day of surgery and localization of bracketing Magtrace® will be performed using Sentimag™ machine. Results of localization will be documented for all four quadrants and any failure of localization signal will be referred back to radiologist for re-localization using other modalities (Magseed® or wire).
Surgery will be performed in accordance with the standard technique and intraoperative confirmation of bracketing localization will be documented. Sentinel node localization will be performed using dual technique with Methylene blue Injection on the day of surgery as the second tracer. Success or failure of sentinel node Magtrace® signal will be documented.
Final histology of the excision specimen will be reviewed to assess for adequacy of excision and any need for further excision in case of close / positive margin will be documented.
Sample size:
As this is a proof-of-concept pilot study, no data currently exists to inform on sample size calculation. Based on the study recruitment number for MagSNOLL study which showed that lesion localization for palpable and impalpable tumor was possible using SPIO (N=32 patients), and accounting for a 10% attrition rate to follow-up, we plan to recruit a total of 35 patients in the study.
Statistical analysis:
Distribution testing will be performed for all continuous variable and parametric or non-parametric tests with be used accordingly to assess any differences of more than 10% in the central measure. Continuous variable will be represented as median with interquartile difference or mean with standard deviation. 95% confidence interval will be calculated for all central measures. A test minimization strategy will be employed to avoid excessive statistical testing. No statistical tests will be performed if a difference of less than 10% exists for the central measure for any given variable and the data will be presented as is. For categorical variable, data will be presented and actual number (n) with percentage and Chi- square or Fischer's exact test will be used to assess any differences. Regression analysis will be utilized to assess for any predictive factors for failure of bracketing localization, if encountered. Simple cost analysis will be performed to assess for any cost differences with the conventional localization method.
Procedures of assessing efficacy of intervention:
Following parameters will be recorded to document the efficacy of intervention and outcomes.
- Accurate localization in the radiology department during injection of Magtrace.
- Preoperative confirmation of localization with magnetic (Sentimag) probe before surgery.
- Intraoperative confirmation of localization with magnetic (Sentimag) probe while resecting the bracketed lesion.
- Postoperative assessment with specimen mammogram and histopathology.
Direct access to source data and documents Data will be collected for patient's baseline health parameters, comorbidities, diagnosis, type of breast cancer, treatments offered, localization methods, type and duration of surgery, post-surgical complications, histological outcomes, reoperations and adjuvant treatments. Data will be stored on Microsoft Excel on King Faisal Specialist Hospital and Research Center servers with access to Principal and co investigators.
Ethics & Regulatory approvals The study proposal was submitted to the local Institutional Review Board and has received ethical approval.
Quality of assurance, data handling, publication policy and finance Data analysis will be performed upon completion of the study and results will be shared locally, nationally and internationally through conferences, forums. Manuscripts will be prepared and submitted for peer review and publication in journals.
No external financial body is involved in the design or conduct of the study. All procedure related costs would have been incurred as part of the patient treatment in any case and no additional procedures are planned or anticipated over and above the normal treatment costs.
Timeline Breast and Endocrine surgery unit and King Faisal Specialist Hospital and Research Center Madinah treats around 300 patients a year. Considering the inclusion criteria, it is anticipated that the recruitment is likely to take between 12 - 18 months and follow up will be completed in the ensuing 6 months to 1 year. This places the total duration of the project between 2 and 3 years from start to completion.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Fayyaz A Mazari, MBBS, MSc, MS, PhD, FRCS, FEBS
- Phone Number: 50847 +966 12667 7777
- Email: fmazari@kfshrc.edu.sa
Study Contact Backup
- Name: Zabihullah Khan, MBBS FRCS
- Phone Number: 50847 +966126677777
- Email: zkhan@kfshrc.edu.sa
Study Locations
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-
-
Madinah, Saudi Arabia
- Recruiting
- King Faisal Specialist Hospital and Research Center
-
Contact:
- Fayyaz A Mazari, MBBS, MSc, MS, PhD, FRCS, FEBS
- Phone Number: 50847 +966 12667 7777
- Email: fmazari@kfshrc.edu.sa
-
Contact:
- Email: fmazari@kfshrc.edu.sa
-
Principal Investigator:
- Fayyaz A Mazari, MBBS, MSc, MS, PhD, FRCS, FEBS
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
All patients with breast cancer undergoing breast conserving surgery requiring bracketing of the area of excision (as determined by the multidisciplinary tumor board) and a sentinel lymph node biopsy for axillary staging.
Exclusion Criteria:
- Patients having mastectomy.
- Patients unfit for breast conserving surgery due to inability to have adjuvant radiotherapy.
- Patients requiring axillary clearance without sentinel node biopsy.
- Patient undergoing breast conserving surgery without need for sentinel node biopsy.
- Patient with metastatic breast cancer requiring palliative surgery for local control.
- Patients not consenting for research.
- Patient with allergy to Magtrace.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Magtrace Bracketing
Patients identified from breast multidisciplinary team meeting who require breast conserving surgery with bracketing required for the area of excision, with sentinel lymph node biopsy simultaneously will be recruited to the study (single intervention arm). Informed consent will be obtained for all patients who agree to take part in the study. Patients who agree to participate will receive Magtrace Injection in the breast one day before surgery. Magtrace will be injected at four points around the area to excised for bracketing. |
Lesion localization procedure will be performed one day before or on the day of surgery. Patients included in the study will have localization of primary cancer / cancers with Magseed® and bracketing with Magtrace® under ultrasound / Mammographic guidance as indicated, in accordance with the local treatment protocol. The Consultant Radiologist using Magtrace® will perform bracketing under image guidance. 0.5ml of Magtrace® will be injected into the breast parenchyma superior, inferior, medial and lateral to the area planned for excision. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Success localization of bracketing Magtrace injection with Magnetic probe
Time Frame: Morning of surgery.
|
A hand held magnetic localization probe (Sentimag) will be used on the morning of surgery by the operating surgeon to localize the signal of Magtrace at four points bracketed around the area of the breast to be excised. For the bracketing localization to be considered successful, signal localization will be required to be present at all four points. |
Morning of surgery.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Successful sentinel node localization with Magnetic probe
Time Frame: Time of surgery
|
Hand held magnetic signal localization probe (Sentimag) will be used to localize Magtrace signal intra-operatively in the ipsilateral axillary lymph node for them to be labelled as sentinel lymph nodes. Second localization agent (Methylene blue) will also be injected in the breast on the morning of surgery as per protocol for dual localization of sentinel nodes. Absence of magnetic signal or blue dye in the lymph nodes will be considered as failure of sentinel node localization. |
Time of surgery
|
|
Duration of surgery
Time Frame: Time of surgery
|
Total duration of surgery from skin incision to complete skin closure and application of dressing will be noted in minutes. |
Time of surgery
|
|
Breast tissue resection weight and volume
Time Frame: Time of surgery
|
Tissue removed at the time of surgery will be weighed using electronic scale in grams. Tissue volume will be calculated based on gross pathology description of the length, breadth and depth of the specimen at the time of cross sectional cutting of specimen for fixation immediately after removal of specimen from the breast. |
Time of surgery
|
|
Resection margin positivity rate (proportion of patient with tumor present at resection margin on final histology)
Time Frame: 2 weeks post surgery.
|
Final histology reports for the resected breast tissue specimen will be reviewed and proportion of patients who have invasive or in-situ breast cancer present at the circumferential resection margin (superior, inferior, medial and lateral) will be calculated. This will be assessed against the accepted departmental standard of 10 - 15%. |
2 weeks post surgery.
|
|
Re-operation rates
Time Frame: 3 months
|
Proportion of patients who required further surgery to achieve a margin clearance (no invasive or in-situ carcinoma on inked edge) either in the form of margin re-excision surgery or completion mastectomy will be calculated. |
3 months
|
|
Post operative complications (immediate and delayed)
Time Frame: 3 months
|
Postoperative complications arising as a direct consequence of surgery will be documented and classified according to the Clavian-Dindo system. This will be done in the immediate post-operative period as well as up to 3 months after surgery. Any re-admissions to hospital due to complications will also be recorded. |
3 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Operator ease of use / acceptability.
Time Frame: Time of intervention
|
Consultant Radiologist performing the Magtrace injection for bracketing will be asked to rate the ease of the bracketing process with Magtrace injection on a linear 1 (very easy) to 10 (very difficult) scale for every patient. |
Time of intervention
|
|
Procedure cost analysis
Time Frame: Time of intervention.
|
The overall cost of the bracketing with Magtrace injection will be calculated based on the standardized cost of consumables, time and slot allocation and compared with the costs of using multiple magnetic seeds and wires. Incremental costs (if any) will be calculated to assess cost effectiveness. |
Time of intervention.
|
Collaborators and Investigators
Investigators
- Principal Investigator: Fayyaz A Mazari, MBBS, MSc, MS, PhD, FRCS, FEBS, King Faisal Specialist Hospital & Research Center
Publications and helpful links
General Publications
- Da Silva M, Porembka J, Mokdad AA, Seiler S, Huth J, Rivers A, Wooldridge R, Chu A, Brown E, Bao J, Farr D, Hansen M, Unzeitig-Barron A, Leitch M, Rao R. Bracketed radioactive seed localization vs bracketed wire-localization in breast surgery. Breast J. 2018 Mar;24(2):161-166. doi: 10.1111/tbj.12854. Epub 2017 Jul 14.
- Lyons W, Lamm R, Duffner ER, Shames J, Willis AI, Lazar M. Bracketed Localization in Breast-Conserving Surgery: Indications and Success Rates From a Single, High Volume, Academic Breast Cancer Center. Am Surg. 2023 Nov;89(11):4373-4378. doi: 10.1177/00031348221111516. Epub 2022 Jun 27.
- Davis KM, Raybon CP, Monga N, Waheed U, Michaels A, Henry C, Spalluto LB. Image-guided Localization Techniques for Nonpalpable Breast Lesions: An Opportunity for Multidisciplinary Patient-centered Care. J Breast Imaging. 2021 Sep 16;3(5):542-555. doi: 10.1093/jbi/wbab061.
- Cheung BHH, Co M, Lui TTN, Kwong A. Evolution of localization methods for non-palpable breast lesions: a literature review from a translational medicine perspective. Transl Breast Cancer Res. 2024 Apr 15;5:12. doi: 10.21037/tbcr-23-49. eCollection 2024.
- Liberman L, Kaplan J, Van Zee KJ, Morris EA, LaTrenta LR, Abramson AF, Dershaw DD. Bracketing wires for preoperative breast needle localization. AJR Am J Roentgenol. 2001 Sep;177(3):565-72. doi: 10.2214/ajr.177.3.1770565.
- Ahmed M, Anninga B, Goyal S, Young P, Pankhurst QA, Douek M; MagSNOLL Trialists Group. Magnetic sentinel node and occult lesion localization in breast cancer (MagSNOLL Trial). Br J Surg. 2015 May;102(6):646-52. doi: 10.1002/bjs.9800.
- Torras I, Cebrecos I, Castillo H, Mension E. Evolution of breast conserving surgery-current implementation of oncoplastic techniques in breast conserving surgery: a literature review. Gland Surg. 2024 Mar 27;13(3):412-425. doi: 10.21037/gs-23-454. Epub 2024 Mar 14.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB#2261285
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Study protocol and informed consent form will be be made available at the time of study registration. Anonymized patient data collected during the study along with the primary and secondary outcomes data used for analysis will be made available at the end of the study in accordance and compliance with the Institutional and National data protection laws.
IPD Sharing Time Frame
Study protocol and informed consent form will be available from the beginning to the end of study and afterwards. Dataset will be available from the end of recruitment to the end of study.
IPD Sharing Access Criteria
All parties with access to ClinicalTrials.gov wil have access to the IPD and supporting information.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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