Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence
- 1 September 2018
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 78 (17), 5144-5154
- https://doi.org/10.1158/0008-5472.can-18-0878
Abstract
For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor-mapping of surgical specimens. We thus evaluated a novel approach for real-time, intraoperative tumor margin assessment. 21 adult patients with biopsy-confirmed squamous cell carcinoma arising from the head and neck (HNSCC) scheduled for standard-of-care surgery were enrolled. Cohort 1 (n=3) received panitumumab-IRDye800CW at an intravenous microdose of 0.06 mg/kg, cohort 2A (n=5) received 0.5mg/kg, cohort 2B (n=7) received 1mg/kg, and cohort 3 (n=6) received 50 mg. Patients were followed 30 days post-infusion and adverse events were recorded. Imaging was performed using several closed- and wide-field devices. Fluorescence was histologically correlated to determine sensitivity and specificity. In situ imaging demonstrated tumor-to-background ratio (TBR) of 2-3, compared to ex vivo specimen imaging TBR of 5-6. We obtained clear differentiation between tumor and normal tissue, with a three-fold signal difference between positive and negative specimens (p89%; fluorescence predicted distance of tumor tissue to the cut surface of the specimen. This novel method of detecting tumor-involved margins in surgical specimens using a cancer-specific agent provides highly sensitive and specific, real-time, intraoperative surgical navigation in resections with complex anatomy which are otherwise less amenable to image guidance.Keywords
Other Versions
Funding Information
- Stanford University School of Medicine (019.171LW.022)
- NIH NCI (R01CA190306, R21CA182953, R21CA179171, T32CA091078)
This publication has 30 references indexed in Scilit:
- A pathology atlas of the human cancer transcriptomeScience, 2017
- Diagnostic Accuracy of Intraoperative Techniques for Margin Assessment in Breast Cancer SurgeryAnnals of Surgery, 2017
- Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using 18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility StudyJournal of Nuclear Medicine, 2016
- Effects of an Unlabeled Loading Dose on Tumor-Specific Uptake of a Fluorescently Labeled Antibody for Optical Surgical NavigationMolecular Imaging & Biology, 2016
- A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian CancerClinical Cancer Research, 2016
- Detection of Melanoma Metastases in Resected Human Lymph Nodes by Noninvasive Multispectral Photoacoustic ImagingInternational Journal of Biomedical Imaging, 2014
- Synthesis and biological evaluation of panitumumab–IRDye800 conjugate as a fluorescence imaging probe for EGFR-expressing cancersMedChemComm, 2014
- Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma.Molecular Imaging & Biology, 2013
- EGF–ERBB signalling: towards the systems levelNature Reviews Molecular Cell Biology, 2006
- Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapyCritical Reviews in Oncology/Hematology, 2001