Stan van Keulen1, Nynke S van den Berg2, Naoki Nishio3, Andrew Birkeland4, Quan Zhou5, Guolan Lu6, Han-Wei Wang7, Lyle Middendorf7, Tymour Forouzanfar8, Brock A Martin9, A Dimitrios Colevas10, Eben L Rosenthal11. 1. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States; Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, the Netherlands. Electronic address: stanvk@stanford.edu. 2. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: nsvdb@stanford.edu. 3. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: nn240@stanford.edu. 4. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: abirkela@stanford.edu. 5. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: qzh@stanford.edu. 6. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: guolanlu@stanford.edu. 7. LI-COR Biosciences, 4647 Superior St, Lincoln, NE 68504, United States. 8. Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, the Netherlands. 9. Department of Clinical Pathology, Stanford University School of Medicine, 300 Pasteur Dr, Palo Alto, CA 94304, United States. Electronic address: brockm@stanford.edu. 10. Department of Medicine, Division of Medical Oncology, University School of Medicine, 269 Campus Drive, Stanford, CA 94305, United States. 11. Department of Otolaryngology, Stanford University School of Medicine, 900 Blake Wilbur Drive, Stanford, CA 94305, United States. Electronic address: elr@stanford.edu.
Abstract
OBJECTIVE: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (<5 mm) are found in 15-30% of head and neck cancer patients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. MATERIALS AND METHODS: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. RESULTS: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. CONCLUSION: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.
OBJECTIVE: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (<5 mm) are found in 15-30% of head and neck cancerpatients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. MATERIALS AND METHODS: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. RESULTS: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. CONCLUSION: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.
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