Near-Infrared Labeling of EGFR+ Cells Can Allow Differentiation between Benign and Metastatic Lymph Nodes

Take-Away Points

• ■ Major focus: Improving ex vivo identification of benign and metastatic lymph nodes for solid tumor staging.

• ■ Key result: Panitumumab-IRDye800CW (anti-EGFR) imaging of resected lymph nodes from patients with solid tumors enhanced ex vivo classification of benign and metastatic lymph nodes.

• ■ Impact: This imaging methodology can increase efficiency and accuracy of lymph node characterization and can be further developed for in vivo imaging during resection surgeries to easily visualize metastatic lymph nodes.

Standard staging of head and neck squamous cell carcinomas is performed by histopathologic assessment of resected lymph nodes from the neck. Metastatic or benign status of resected lymph nodes can be used in the tumor, node, metastasis (TNM) staging system to stage patient tumors. Proper staging of tumors is critical for determining the optimal treatment plan. Current practice requires assessing as many as possible collected lymph nodes for staging. Lymph nodes are typically analyzed by hematoxylin-eosin (H-E) staining to detect differences in tissue architecture for benign or metastatic classification, which can be a time-consuming and subjective process. Nishio et al describe the use of panitumumab-IRDye800CW (anti–epidermal growth factor receptor [EGFR]) as a near-infrared fluorescently labeled agent to selectively label metastatic lymph nodes during ex vivo evaluation.

In this single-center, nonrandomized, phase I study, 22 patients underwent surgical resection of primary tumors, as well as either a unilateral or bilateral neck dissection. Panitumumab-IRDye800CW was infused into patients 1–5 days prior to surgery with an average dose of 0.67 mg/kg (range, 0.26–1.05 mg/kg). Resected lymph nodes were subjected to closed-field fluorescence imaging, as well as standard H-E staining, to determine the sensitivity and specificity of fluorescent EGFR labeling. Nishio et al quantified two imaging parameters: (a) mean fluorescence intensity (MFI) and (b) signal-to-background (SBR) and compared these results to histopathologic findings of the lymph nodes. Metastatic lymph nodes had significantly higher MFI and SBR than benign lymph nodes. Taking both MFI and SBR into account, metastatic lymph nodes could be identified with high sensitivity (84.6%), specificity (94.0%), negative predictive value (99.3%), and an acceptable positive predictive value (36.2%).

In all, using panitumumab-IRDye800CW to label metastatic lymph nodes could reduce the total number of lymph nodes required for histologic determination of benign or metastatic status. Additionally, regular implementation of the described anti-EGFR labeling approach could help to increase standardization and efficacy of lymph node identification.

Highlighted Article

• Nishio, N, van den Berg NS, van Keulen S, et al. Optical molecular imaging can differentiate metastatic benign lymph nodes in head and neck cancer. Nat Commun 2019;10:5044. doi: https://doi.org/10.1038/s41467-019-13076-7