Background Tissue with Native Target Expression Can Determine Presence of Nodal Metastasis in Head and Neck Squamous Cell Carcinoma Patients Infused with Targeted Fluorescent Tracers.

PURPOSE: Survival and treatment intensity in patients with head and neck squamous cell carcinoma (HNSCC) is determined by the presence of lymph node (LN) metastasis, and as a result surgical removal of potentially affected LN remains a mainstay practice. Fluorescence guided surgery (FGS) using targeted optical agents is an expanding field that shows great potential for aiding diagnosis of metastatic LN. Given variations in fluorescence background, a reference standard for regions of interest is necessary for cross patient comparison. The present study aims to determine whether tissue with native target expression can be used as a background to determine metastatic LN in patients with HNSCC infused with anti-epidermal growth factor receptor (EGFR) targeted imaging agents.

PROCEDURES: Twenty-two patients infused with panitumumab-IRDye800 or cetuximab-IRDye800 prior to surgery were included. Fluorescence imaging and analysis was performed on resected LNs (N = 843) using the submandibular glands (SMG) and skin as reference standard tissue with known EGFR antigen expression.

RESULTS

Sixteen patients (72.7%) had at least one positive LN on final pathology. The LN to SMG (LN/SMG) and LN to skin (LN/skin) ratios were significantly higher in metastatic LN compared to benign LN (p < 0.0001 for both). Using patient-specific ratios to determine an optimal LN/skin cutoff was the most sensitive (95.2%) and directly comparing the LN/skin ratio of all patients to determine a cutoff was the most specific (86.3%).

CONCLUSIONS

In HNSCC patients infused with a molecularly targeted fluorescent tracer, endogenous expression of the target antigen can be used as a reference standard to detect LN metastasis. Additionally, the performance of the background in determining metastatic LN can be improved by utilizing patient-specific reference standards.