Abstract

Abstract The status of lymph nodes is an important factor in staging cancer since the transport of primary cancer cells via the lymphatic system is one of the main pathways of metastasis to distant organs. During cancer surgery, lymph node status is evaluated via sentinel lymph node biopsy (SLNB), which involves the removal and analysis of the first (or sentinel) nodes along the lymphatic chain of nodes draining the primary tumor. The sentinel nodes are identified through the accumulation of a radioactive agent (technetium-99) and/or isosulfan blue dye within the nodes, frequently resulting in the resection of multiple nodes for subsequent, often time-consuming, histopathological analysis. The majority of these resected nodes are found by histological analysis to be normal, leading to unnecessary complications, including increased risk of lymphedema. Thus, a method for the in situ assessment of node status could reduce the number of normal lymph nodes that are resected. In this study we evaluated the sensitivity and specificity of three-dimensional optical coherence tomography (OCT) for the intraoperative assessment of metastatic disease in lymph nodes. OCT is the optical analogue to ultrasound imaging, except images are based on the optical scattering properties of near-infrared light. Real-time OCT with micron-scale resolution affords optical biopsies of tissue for immediate feedback. Intraoperative OCT imaging was conducted on human lymph nodes resected from 49 subjects during breast and, head and neck cancer surgeries. Three-dimensional OCT datasets were recorded ex vivo from one or more locations per node, and marked with surgical ink for subsequent correlation to histology. These lymph nodes then underwent the standard histological processing. A double-blinded study was performed comparing the assessment of OCT datasets to the co-registered histological findings. Three-dimensional -OCT datasets from 206 sites were independently analyzed by six observers and classified as cancerous or non-cancerous. Seventy-nine sets were identified as unsuitable for OCT analysis due to insufficient nodal tissue within the imaged field-of-view. Early training classification results from three of the six observers resulted in a sensitivity of 64.8% and a specificity of 73.3% for identifying metastatic lymph nodes intraoperatively, in real-time, compared to the gold standard of post-operative histopathology. Final study results are expected to improve with observer training and a decision tree for interpreting OCT images. Our initial imaging studies of resected lymph nodes in human cancer subjects demonstrate the potential of OCT as a technique for real-time optical biopsy of lymph nodes for the intraoperative staging of cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-23.

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