Abstract
In most oral cancer patients, surgical treatment includes resection of the primary tumor combined with excision of lymph nodes (LNs), either for staging or for treatment. All LNs harvested during surgery require tissue processing and subsequent microscopic histopathologic assessment to determine the nodal stage. In this study, we investigated the use of the fluorescent tracer cetuximab-800CW to discriminate between tumor-positive and tumor-negative LNs before histopathologic examination. Here, we report a retrospective ad hoc analysis of a clinical trial designed to evaluate the resection margin in patients with oral squamous cell carcinoma (NCT02415881). Methods: Two days before surgery, patients were intravenously administered 75 mg of cetuximab followed by 15 mg of cetuximab-800CW, an epidermal growth factor receptor-targeting fluorescent tracer. Fluorescence images of excised, formalin-fixed LNs were obtained and correlated with histopathologic assessment. Results: Fluorescence molecular imaging of 514 LNs (61 pathologically positive nodes) could detect tumor-positive LNs ex vivo with 100% sensitivity and 86.8% specificity (area under the curve, 0.98). In this cohort, the number of LNs that required microscopic assessment was decreased by 77.4%, without missing any metastases. Additionally, in 7.5% of the LNs false-positive on fluorescence imaging, we identified metastases missed by standard histopathologic analysis. Conclusion: Our findings suggest that epidermal growth factor receptor-targeted fluorescence molecular imaging can aid in the detection of LN metastases in the ex vivo setting in oral cancer patients. This image-guided concept can improve the efficacy of postoperative LN examination and identify additional metastases, thus safeguarding appropriate postoperative therapy and potentially improving prognosis.
Highlights
In oral squamous cell carcinoma (OSCC), the presence of lymph node (LN) metastasis has a major impact on prognosis and is associated with a significantly reduced survival [1, 2]
We explored the potential of Fluorescence molecular imaging (FMI) using cetuximab-800CW for discrimination between pathologically positive and negative LNs prior to histopathological examination
This study demonstrates that Epidermal Growth Factor Receptor (EGFR)-targeted FMI based on intravenously administered cetuximab-800CW
Summary
In oral squamous cell carcinoma (OSCC), the presence of lymph node (LN) metastasis has a major impact on prognosis and is associated with a significantly reduced survival [1, 2]. Assessment of LN status is important for determining the postoperative treatment strategy of the neck and consists of clinical assessment and preoperative radiographic imaging (i.e. magnetic resonance imaging, computed tomography or ultrasound). If clinically suspicious LNs (cN+) are identified, a therapeutic neck dissection is indicated. The neck dissection specimen is macroscopically analyzed by the pathologist for the presence of LNs [5], and all LNs are sectioned and stained with H&E or cytokeratin for microscopic evaluation. Other techniques for identifying LN metastasis are not clinically available yet. It is interesting to explore other methods to identify metastasis in LNs, especially when the tissue is intact, prior to routine processing
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