Use of Magtrace Bracketing for Excision of Lesion and Sentinel Lymph Node Localization in Breast Conserving Surgery for Breast Cancer

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:

1. Assessing Feasibility: Determining whether bracketed Magtrace® Localization can be reliably performed in a clinical setting.
2. Non-inferiority to current localization methods for bracketing.
3. 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.