MR Lymphography and Magnetic Sentinel Lymph Node Biopsy in Melanoma Patients

Study Overview
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Brief Summary
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The sentinel lymph nodes (SLNs) are the first lymph nodes (LNs) to drain the tumor site and therefore the first LNs to bare metastases. Hence the importance to investigate these LNs for the best treatment strategy. Current-standard-of-care for melanoma patients with a melanoma stage of pT1b or higher, involve a surgical procedure, referred to as SLN biopsy (SLNB). The SLNB procedure involves a combined detection procedure using a radio-active tracer and blue dye followed by surgical dissection and evaluation of the LNs at the histopathology department. Due to the use of radioisotopes, this procedure suffers from several disadvantages such as limited availability, strict rules and regulations, degradation time in patient and radioactive load for user and patient. To overcome the limitations of a radioactive tracer, a magnetic SLNB was developed which is facilitated by super paramagnetic iron-oxide (SPIO) nanoparticles. This potentially offers numerous benefits making surgery planning more flexible: no exposure to radiation, easy accessibility of the tracer, long shelf life and long half time in the patient. However, the currently available magnetometer for intraoperative detection of SPIO-enhanced LNs is hampered by a relatively low detection depth, biological noise, and effects of surgical equipment. Therefore, surgeons need to switch to plastic or carbon equipment and the system needs to be balanced prior to each measurement, which increases the surgery time. A new and effective way to localize SPIOs is differential magnetometry (DiffMag). This patented detection principle, developed by MD&I group at University of Twente (UT), utilizes the nonlinear magnetic response of nanoparticles. An additional advantage of SPIOs is their visibility on MRI, which could provide mapping the SLNs preoperatively. Especially in patients with melanomas on the abdomen or back this would be very useful to see which lymph node stations are connected to the melanoma. In addition, studies have shown that SPIOs are absorbed into lymph nodes in different ways, depending on the presence of metastases. SPIO-enhanced MR lymphography could therefore provide an opportunity for a non-invasive preoperative assessment of nodal status. In this pilot study the investigators want to evaluate the clinical use of the DiffMag handheld probe. Moreover, the investigators want to map the lymph nodes (metastases) preoperatively using MR lymphography.

Official Title
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MR Lymphography and Magnetic Sentinel Lymph Node Biopsy in Melanoma Patients Measured With DiffMag

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Device: Magnetic sentinel lymph node biopsy by use of Magtrace®, in combination with SentiMag® and DiffMag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with melanoma of the upper or lower extremities scheduled for SLNB; Willing to & able to write informed consent from the subject prior to participation; Willing to & capable of following study procedures; Is older than 18 years; Speaks and understand the Dutch language Exclusion Criteria: Intolerance / hypersensitivity to iron or dextran compounds Pregnant or lactating patients; Patients having a pacemaker. Patients non eligible for MRI investigation (pacemakers or other implantable devices in the chest wall and/or lower body, claustrophobic, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: MelaDiff<br>Patients with melanoma of the extremities included in the protocol. Preoperative, patients will receive two MRI-scans and a magnetic tracer injection at the primary tumor site. During surgery, SLNs will be detected using two types of magnetometers (SentiMag® & DiffMag) in combination with Magtrace®, in addition to the standard procedure. | Device: Magnetic sentinel lymph node biopsy by use of Magtrace®, in combination with SentiMag® and DiffMag<br>* In addition to the standard procedure, SLNs will be detected using two types of magnetometers (SentiMag® & DiffMag) in combination with SPIO particles (Magtrace®).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| True positive/False negative rate for a magnetic SLN detection measured by DiffMag system compared to radioactive detection. | Determining the feasibility of SLN detection/localization in melanoma patients using a magnetic tracer (Magtrace®) and hand-held magnetometer DiffMag. | through study completion, an average of 1 year | 
| True positive/False negative rate for a magnetic SLN detection measured by Sentimag system compared to radioactive detection. | Determining the feasibility of SLN detection/localization in melanoma patients using a magnetic tracer (Magtrace®) and hand-held magnetometer Sentimag. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| True positive/False negative rate for metastatic SLN using ex vivo MRI | Determining the feasibility of LN mapping with preoperative SPIO-enhanced MR lymphography and examining the use of SPIO-enhanced MR lymphography for LN staging. | through study completion, an average of 1 year | 
| True positive/False negative rate for metastatic SLN using in vivo MRI | Determining the feasibility of LN mapping with preoperative SPIO-enhanced MR lymphography and examining the use of SPIO-enhanced MR lymphography for LN staging. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic sentinel lymph node biopsy (SLNB), Lymph node detection, Lymph node staging, MR lymphography, Super paramagnetic iron-oxide (SPIO) nanoparticles