Exploring an Alternative Pre-operative SLN Mapping Method Using a Magnetic Tracer and MRI for Melanoma Patients

Study Overview
=================
Brief Summary
-----------------
Sentinel lymph node biopsy (SLNB) is crucial in the management of malignant melanoma treatment and is currently performed by pre-operatively inject a colloid nanomaterial labeled with Technetium (99mTc) as radioactive tracer. Intra-operatively, Patent Blue (PB) will be injected to improve the visualization of the lymphatic tract. However, current pre-operative SLN mapping technique is associated with disadvantages as radiation exposure for both patients and health care staff and logistic challenges, because of time constraints due to short half-live time of 99mTc. Superparamagnetic iron oxide (SPIO) is a non-radioactive technique using a magnetic tracer (Magtrace® (Endomagnetics Ltd.)) to identify SLNs. Several studies showed that SPIO is non-inferior to dual tracing with 99mTc and PB in breast cancer patients. SPIO is expected to be non-inferior to dual tracing with 99mTc and PB in melanoma patients. However, further research is needed to demonstrate the use of SPIO in pre-operative MRI scanning. The primary objective of this study is to evaluate the feasibility and diagnostic accuracy of pre-operative MRI scanning using SPIO compared to lymphoscintigraphy (LS) and single-photon emission computed tomography/computed tomography (SPECT/CT) using 99mTc for identifying SLN status in melanoma patients.

Detailed Description
-----------------
Rationale: Sentinel lymph node biopsy (SLNB) is crucial in the management of malignant melanoma treatment and is currently performed by pre-operatively inject a colloid nanomaterial labeled with Technetium (99mTc) as radioactive tracer. Intra-operatively, Patent Blue (PB) will be injected to improve the visualization of the lymphatic tract. However, current pre-operative SLN mapping technique is associated with disadvantages as radiation exposure for both patients and health care staff and logistic challenges, because of time constraints due to short half-live time of 99mTc. Superparamagnetic iron oxide (SPIO) is a non-radioactive technique using a magnetic tracer (Magtrace® (Endomagnetics Ltd.)) to identify SLNs. Several studies showed that SPIO is non-inferior to dual tracing with 99mTc and PB in breast cancer patients. SPIO is expected to be non-inferior to dual tracing with 99mTc and PB in melanoma patients. However, further research is needed to demonstrate the use of SPIO in pre-operative MRI scanning. Objective: The primary objective of this study is to evaluate the feasibility and diagnostic accuracy of pre-operative MRI scanning using SPIO compared to lymphoscintigraphy (LS) and single-photon emission computed tomography/computed tomography (SPECT/CT) using 99mTc for identifying SLN status in melanoma patients. A secondary objective is to assess the feasibility and diagnostic accuracy of SPIO/magnetometer (Sentimag®, Endomagnetics Ltd.) in comparison with dual trace gold standard (99mTc and PB) in SLN procedures in melanoma patients. Study design: A prospective single-arm feasibility study will be performed at the department of Surgical oncology at Zuyderland Medical Center Sittard, the Netherlands. Study population: Adult patients (≥18 years) with primary melanoma stage I-II and an indication for wide local excision (1 cm) and SLN procedure will be included in the study. Intervention (if applicable): All patients will undergo lymphatic mapping with a SPIO tracer (Magtrace®), 99mTc and PB. Main study parameters/endpoints: The concordance in SLN detection rate (sensitivity and specificity) of SPIO/MRI and LS and SPECT/CT using 99mTc. The concordance in SLN detection rate (sensitivity and specificity) of SPIO/magnetometer and the gold standard dual trace technique using 99mTc/Gamma probe and PB. Additionally, the number of post-injection (skin) reactions, complication and adverse events will be noted.

Official Title
-----------------
Exploring an Alternative Pre-operative Sentinel Lymph Node Mapping Method Using a Magnetic Tracer and MRI for Melanoma Patients

Conditions
-----------------
Melanoma

Intervention / Treatment
-----------------
* Diagnostic Test: Diagnostic Test: Sentinel node mapping using MRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients ≥18 years of age at the time of consent; Histological confirmed melanoma (patient must have primary cutaneous melanoma with Breslow thickness ≥ 0.8-2.0mm with or without ulceration or <0.8mm with ulceration (pT1b - pT2b, AJCC 8th edition)); Indication for wide local excision (margin 1 cm) and SLN procedure; Patients should be willing and able to provide informed consent. Exclusion Criteria: Intolerance/hypersensitivity to 99mTc-nanocolloid, PB, iron or dextran compounds; Iron overload disease; Pregnant or breast-feeding women; Previous surrounded lymph node surgery; Patients with head and neck melanomas; Standard MRI exclusion criteria; Implantable (electrical) devices (e.g. pacemaker, cochlear implants, neurostimulator); Any other metal implants; Claustrophobia; MR-incompatible prosthetic heart valves; Patients who are unable or refuse to provide informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melanoma patients<br>All patients will undergo lymphatic mapping with SPIO, 99mTc and PB. | Diagnostic Test: Diagnostic Test: Sentinel node mapping using MRI<br>* Sentinel lymph node mapping in melanoma patients using a magnetic tracer and MRI<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diagnostic accuracy of SPIO/MRI and LS+SPECT/CT and 99mTc to identify SLN | The diagnostic accuracy of SPIO/MRI and LS+SPECT/CT and 99mTc to identify SLN will be expressed as sensitivity and specificity, and positive and negative predictive values, including their 95% exact binomial confidence intervals. MRI image analyses will be performed by two independent professionals. | Before surgery (MRI scanning and scintigraphy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The diagnostic accuracy of SPIO/magnetometer and PB, 99mTc and Gamma probe | The diagnostic accuracy of SPIO/magnetometer and PB, 99mTc and Gamma probe will be expressed as sensitivity and specificity, and positive and negative predictive values, including their 95% exact binomial confidence intervals . | During SLNB (surgery) | 
| Comparison between 99mTc injection + LS + SPECT/CT time vs SPIO injection + MRI | Time/duration of 99mTc injection + LS + SPECT/CT and time/duration of SPIO injection + MRI will be compared | During SLNB (surgery) | 
| Number of post-injection (skin) reactions, complication and adverse events | Descriptive only | At 10-14 days and at 3 months after the procedure | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Magnetic tracer, Sentinel lymph node, Melanoma, MRI