Thyroglobulin Point of Care Assay for Rapid Detection of Metastatic Differentiated Thyroid Carcinoma

Background: Despite a favorable prognosis, metastatic cervical lymph nodes (LN), are not uncommon among patients with differentiated thyroid cancer (DTC). Current guidelines recommend that a suspicious cervical LN on neck ultrasound (US) should be investigated with fine needle aspiration biopsy for cytology (FNAC) and for thyroglobulin (Tg) measurement (FNA-Tg), using saline washout of the needle content. Since Tg is a protein produced exclusively by thyroid follicular cells, a positive FNA-Tg result establishes the diagnosis of metastatic DTC. Currently, following LN biopsy, a patient must wait days to weeks to receive results, that directly impacts the treatment plan. This delay may be solved by a point of care assay of the washout Tg (POC-Tg), drawn from a suspicious cervical LN. Another potential novel usage of POC-Tg is the evaluation of suspicious LN found during neck surgery for known or suspicious DTC. Here, the POC-Tg may save the time needed for the completion of 'frozen section'. The study product: POC-Tg is a lateral flow immunoassay for Tg, able to detect within minutes Tg at concentration equal to 5 ng/mL and above (the midrange of the accepted cut-off). Methods: The multi-center validation study will include 100 patients in the FNA clinic, and 150 LN (dissected from 50-150 patients) in the operating room (OR). Each LN will be evaluated using both the formal accepted method (in the FNA clinic, the combination of FNAC and FNA-Tg; and frozen section in the OR), and the novel POC-Tg. Clinical decisions will be made according to the formal evaluation only. In a retrospective analysis, the investigators will estimate the sensitivity and specificity of the POC-Tg and the formal accepted method against the reference ('gold') standard (cytology, histology and follow-up US in the FNA clinic setting, and final histology in the OR setting).