Abstract
Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%–30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer–device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50–100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes.
Highlights
Squamous cell carcinoma (SCC) is a malignant tumor of epithelial origin
Ravasz et al examined the relation of local recurrence with the presence or absence of tumors at the surgical margin, which was combined with other indications of postoperative radiotherapy [4]
Detection of NIR Signals from a Mouse Bearing Head and Neck Tumors that Infiltrated to the Mylohyoid (Neck) Muscle and Metastasized to the Lungs The NIR signals from the bulk of the primary tumor were very strong and oversaturated the detector (Figure 2A)
Summary
Squamous cell carcinoma (SCC) is a malignant tumor of epithelial origin. More than 90% of all head and neck cancers are SCC [1]. Standardized reporting of head and neck cancer resections, according to guidelines issued by the UK Royal College of Pathologists, was introduced as a routine procedure in 1998 [5]. They reported the frequency, type, and morphological features of involved margins and assessed the influence of tumor site and pathological tumor and node stages from 301 radical resection specimens for oral/oropharyngeal SCC (cases from 1998 to 2005). It is reasonable to assume that large tumors are more difficult to resect, given the anatomical restraints at many sites within the Intraoperative Optical Guidance for Metastatic Head and Neck Cancer Surgery oral cavity and oropharynx. It was noted that it is difficult to “visualize” particular growth patterns and other features of the deep advancing tumor front, both pre- and intraoperatively, as those particularities are only evident after microscopy [5]
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