Magnetic Sentinel Lymph Node Mapping in Oral Squamous Cell Carcinoma: A Phase I Feasibility and Validity Clinical Trial

Patients undergoing surgery to remove a proven T1-T2 oral squamous cell carcinoma (SCC) and associated elective neck dissection (END). Patients will receive a single dose of MagTrace or FerroTrace magnetic tracer (Endomag, Cambridge UK or Ferronova, Adelaide Australia). FerroTrace will be used on the first patient, and thereafter the selected tracer will be at the discretion of the principal investigator. The tracer will be delivered via intra-oral sub mucosal injection around the tumour in 5 injections at 12-, 3-, 6-, and 9- o’clock positions around the periphery of the tumour and then another injection deep to the tumour. The total dose for the first injection will be 0.5ml (5 x 100ul), and if this injection volume is not sufficient to demonstrate feasibility to locate the sentinel nodes in surgery, the dose will be increased at the discretion of the principal investigator, but to no more than 2ml (5 x 400ul). Patients will undergo MRI prior to and then following tracer injection to localize lymph nodes (LNs) with tracer uptake and assess tracer distribution within nodes. Areas of low signal intensity thought to represent putative SLNs will be documented. The first patient will undergo the MRI both the day before and the day of surgery. Subsequent patients will have the MRI timing decided at the discretion of the principal investigator. Surgical resection of the oral cancer will be carried out prior to treatment of the neck. Prior to surgical removal of neck nodes, the hand-held magnetometer probe will be used to conduct an initial detection survey of the entire cervical lymph node basin to identify the areas of increased magnetic activity representing putative SLNs. The probe, in conjunction with pre-operative imaging, will be used to find the putative SLN, which will be identified if the magnetic reading exceeds 3 standard deviations above the mean normal tissue background count and/or if the node demonstrates a colour change to black/brown due to the stain of the tracer. If more than 4 LNs meet these criteria, at least 4 SLNS with the highest magnetic activity will be excised and denoted putative SLNs. After removal of all SLNs meeting these criteria, the magnetometer probe will be placed back within the nodal basin to ensure that no substantial residual magnetic activity remains. After removal of all sentinel lymph nodes (SLNs), all participants will undergo a planned END. Lymph node levels I, II (including IIB), III and IV will be removed at the discretion of the surgeon and following hospital protocols. Bilateral neck dissections will be performed when primary lesions involve the midline or in the case of tumours less than 1 cm from the midline with evidence of contralateral drainage on pre-operative serial MRI at the discretion of the surgeon and following clinical team consensus. All SLNs will be labeled individually according to the surgical location. These will be fixed in formalin and cut in a transverse fashion along the long axis every 2mm. Slides from these sections will undergo initial evaluation by means of standard hematoxylin-eosin (H&E) staining. SLNs with findings of metastases on H&E assessment will be deemed positive nodes. SLNs that are negative for metastases on H&E assessment will be further evaluated with immunohistochemical staining for pancytokeratin markers. Non-SLNs in the END will undergo routine histopathological analysis with H&E staining of a single section carried out along the longitudinal axis of the node. Putative SLNs will undergo Prussian blue staining to identify presence of magnetic particles. We will evaluate the feasibility and safety of the new technology. Data surrounding timings of tracer injection and flow to first and second echelon nodes will be collected to optimize timing of surgery. SLN detection rate will be recorded and tabulated for each patient and we will also record the rate of SLN detection per node, malignancy detection rate in participants, and the negative predictive value (NPV), ie. whether a negative SLN will predict negativity of the other cervical LNs.