A Scoping Review of Ongoing Fluorescence‐Guided Surgery Clinical Trials in Otolaryngology

Abstract

Objective: Fluorescence-guided surgery (FGS) is a rapidly developing intraoperative technology, and many contrast agents are currently under investigation. We sought to provide a review of the current state of FGS clinical trials in Otolaryngology, emphasizing its oncologic applications.Methods: According to the preferred reporting Items for systematic reviews and meta-analyses (PRISMA) workflow for scoping reviews, a clinical trial search was performed across multiple international clinical trials registries, searching for permutations of "fluorescence," "tumor," "surgery," and "nerve" to identify all relevant studies. Studies that were active, enrolling, or soon to be enrolling patients undergoing head and neck surgery were included.Results: Nineteen studies were eligible for inclusion. Seventeen studies are focused on FGS for oncologic resection and lymph node detection. One study assesses peripheral nerve fluorescence, and one evaluates normal parathyroid function after thyroidectomy. Contrast agents under development are conjugated to fluorophores that excite in the 800 nm (indocyanine green), 410 nm (5-aminolevulinic acid), 700 nm (Cyanine 5.5), and 525 nm ranges (fluorescein derivatives).Conclusion: Presently, there are 19 ongoing trials investigating novel FGS contrast agents for their safety, efficacy, and utility in Otolaryngology-Head and Neck Surgery. These agents rely on unique fluorophores and absorption ranges in the near-infrared and visible light spectra. FGS studies are expanding within Otolaryngology-Head and Neck Surgery with profound implications in oncologic surgery, lymph node detection, and anatomic and functional assessment.

A fluorescent photoimmunoconjugate for imaging of cholesteatoma

“…Confirmatory tests with Cet-AF647 conjugate demonstrates localization reliability of this compound. While previous studies using fluorescent labeling for intraoperative tissue localization in the head and neck area have primarily focused on tissues with increased metabolic activity, primarily cancer cells, this study represents one of the first to successfully apply similar principles to benign disease without the aid of differential metabolic activity 24 . Furthermore, the unique photoactivation properties of PICs offers the potential for therapeutic targeted tumor ablation following appropriate localization 26 – 29 .…”

A Fluorescent Photoimmunoconjugate For Imaging of Cholesteatoma

“…Con rmatory tests with Cet-AF647 conjugate demonstrates localization reliability of this compound. While previous studies using uorescent labeling for intraoperative tissue localization in the head and neck area have primarily focused on tissues with increased metabolic activity, primarily cancer cells, this study represents one of the rst to successfully apply similar principles to benign disease without the aid of differential metabolic activity 22 . Furthermore, the unique photoactivation properties of PICs offers the potential for therapeutic targeted tumor ablation following appropriate localization [23][24][25][26] .…”

“…A promising candidate marker for intraoperative localization of cholesteatoma is EGFR, since skin cysts are known to overexpress this marker compared to adjacent tissues of the head and neck 9,19 . Fluorescent epidermal growth factor receptor (fEGFR) antibodies are drugs that localize selectively to tissues with squamous hyperplastic processes with overexpression of EGFR, and fEGFR antibodies have been used in head and neck oncology to improve localization accuracy and effectiveness of surgical excision [20][21][22] . Further innovations with other photosensitizer immune conjugates (PICs), most notably cetuximabbenzoporphyrin derivative (Cet-BPD), have further re ned ability for localization of EGFR-positive tumors cells through selective activation of uorescence following metabolism and cleavage of the photosensitizer, with secondary advantage of targeted therapeutic tumor ablation through photoactivation of the immune conjugates once they are appropriately localized [23][24][25][26] .…”

Nanoparticle‐assisted, image‐guided laser interstitial thermal therapy for cancer treatment

“…Fluorescence imaging is a widely used method for bioimaging cells and tissues in vitro and in vivo, and also has promising applications for fluorescence‐guided surgery (Crawford et al, 2021; X. Li et al, 2021; Tanioka et al, 2021; Wolfbeis, 2015). Synthetic fluorescence probes and labels are used to make the sample of interest fluorescent.…”