The Clinical Application of Fluorescence-Guided Surgery in Head and Neck Cancer

Abstract

Although surgical resection has been the primary treatment modality of solid tumors for decades, surgeons still rely on visual cues and palpation to delineate healthy from cancerous tissue. This may contribute to the high rate (up to 30%) of positive margins in head and neck cancer resections. Margin status in these patients is the most important prognostic factor for overall survival. In addition, second primary lesions may be present at the time of surgery. Although often unnoticed by the medical team, these lesions can have significant survival ramifications. We hypothesize that realtime fluorescence imaging can enhance intraoperative decision making by aiding the surgeon in detecting close or positive margins and visualizing unanticipated regions of primary disease. The purpose of this study was to assess the clinical utility of real-time fluorescence imaging for intraoperative decision making. Methods: Head and neck cancer patients (n 5 14) scheduled for curative resection were enrolled in a clinical trial evaluating panitumumab-IRDye800CW for surgical guidance (NCT02415881). Open-field fluorescence imaging was performed throughout the surgical procedure. The fluorescence signal was quantified as signal-to-background ratios to characterize the fluorescence contrast of regions of interest relative to background. Results: Fluorescence imaging was able to improve surgical decision making in 3 cases (21.4%): identification of a close margin (n 5 1) and unanticipated regions of primary disease (n 5 2). Conclusion: This study demonstrates the clinical applications of fluorescence imaging on intraoperative decision making. This information is required for designing phase III clinical trials using this technique. Furthermore, this study is the first to demonstrate this application for intraoperative decision making during resection of primary tumors.

Intraoperative Tumor Assessment Using Real-Time Molecular Imaging in Head and Neck Cancer Patients

“…It is widely recognized that open-field optical imaging is subject to a significant number of external variables such as interference from external light, surface reflectance, and camera placement. 16,22 Yet, it remains difficult to standardize intraoperative data acquisition; the wound cavity depth differs per case, the camera distance to tissue varies per operator and area of interest, the angle of viewing is variable, and ambient light conditions are often different in each operating room. 23 As a result, it is simply not possible to perform rigorous imaging analysis, which controls for these variables.…”

“…The TBRs were calculated by dividing the signal of the area of interestethe primary tumoreto that of background; buccal mucosa in the oral lesions, and gross tumor-negative skin for cutaneous lesions. 15,16 The mean fluorescence signal of the primary tumor was extracted by averaging 10 measurements of circular regions of interest (ROIs) over the gross tumor. The surgeon delineated the tumor area by visual inspection and palpation.…”

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

“…Therefore, targeted optical imaging, which depends on the binding of antibodies to antigens or ligands to receptors, is needed to replace nontargeted optical imaging. Clinical trials of targeted tumourspecific fluorescence imaging conducted in different malignancies have shown remarkable success [14][15][16][17]. Though ICG can be used in humans, it lacks active groups to conjugate with ligands or antibodies.…”

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

“…[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.…”