Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma

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 (<5mm) 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 5mm (n=160) of the cut surface. To detect tumor within 2mm 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 6.3mm. Conclusion Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5mm 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.

Probe‐based fluorescence dosimetry of an antibody‐dye conjugate to identify head and neck cancer as a first step to fluorescence‐guided tissue preselection for pathological assessment

“…18 In the current study, we demonstrate that the fluorescence dosimetry can distinguish tumor from normal tissue in formalin-fixation tissue sections with high diagnostic accuracy (AUC = 0.86). The current study assesses the clinical application of fluorescenceguided tissue preselection for differentiation of the cancerous tissue from normal tissue in an ex vivo setting using a novel contact probe-based fluorescence dosimeter device.…”

“…18,25 Briefly, the agarose in water solution was heated to 80 C and allowed to cool down to 45 C before adding bovine blood, intralipid while continuous stirring to ensure homogeneous distribution of the compounds, after which the mixed solution was separated with different concentrations of IRDye800CW; 18,25 Briefly, the agarose in water solution was heated to 80 C and allowed to cool down to 45 C before adding bovine blood, intralipid while continuous stirring to ensure homogeneous distribution of the compounds, after which the mixed solution was separated with different concentrations of IRDye800CW;…”

“…To validate the fluorescence dosimeter for IRDye800CW, a tissue-mimicking phantom with homogenous IRDye800CWcarboxylate distribution was created in 1% agarose (Life Technologies, Carlsbad, California), 1% whole bovine blood (Sigma-Aldrich, Saint Louis, Missouri), and 1% intralipid emulsion (Sigma-Aldrich), as previously described by us. 18,25 Briefly, the agarose in water solution was heated to 80 C and allowed to cool down to 45 C before adding bovine blood, intralipid while continuous stirring to ensure homogeneous distribution of the compounds, after which the mixed solution was separated with different concentrations of IRDye800CW;…”

“…[4][5][6][7] Accurate sampling of tissue samples to confirm adequate resection is crucial for this technique to be effective. 9,[17][18][19] However, despite the rapid growth of fluorescence imaging, quantifiable fluorescence measurements using an open-field imaging system remain challenging because fluorescence imaging is a noncontact imaging technique and consequently is highly sensitive to lighting variations, due to irregular and nonflat tissue surfaces, and the operating room environment. 8 To improve surgical outcome and margin assessment accuracy, tumor-specific antibody-based fluorescence imaging has been proposed to achieve demarcation and differentiation of cancerous from healthy adjacent tissue.…”

“…16 We have previously demonstrated that our near-infrared fluorescently labeled anti-EGFR antibody, panitumumab-IRDye800CW, is highly sensitive and specific for HNSCC. 9,[17][18][19] However, despite the rapid growth of fluorescence imaging, quantifiable fluorescence measurements using an open-field imaging system remain challenging because fluorescence imaging is a noncontact imaging technique and consequently is highly sensitive to lighting variations, due to irregular and nonflat tissue surfaces, and the operating room environment. Dosimetry has proven itself valuable for monitoring drug delivery in photodynamic therapy (PDT), where it provides a quantitative measurement of photoactivatable drug dose within the targeted region.…”