Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but have the greatest potential impact for improving patient care when the surgeon has limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in OPSCC patients. PATIENTS AND METHODS: 12 consecutive patients with OPSCC were enrolled as part of a non-randomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: Results from this OPSCC patient cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Establishing a role for the oral microbiome in infectious complications following major oral cavity cancer surgery.

Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.

Development of a plant-based surgical training model for fluorescence-guided cancer surgery.

BACKGROUND: Fluorescence-guided surgery (FGS) can help surgeons to discriminate tumor tissue from adjacent normal tissues using fluorescent tracers. METHODS: We developed a surgical training model, manufactured using sustainable vegetable organic material with indocyanine green (ICG)-containing "tumor." Surgeons evaluated the model with both the closed-field and endoscopic fluorescence imaging devices and assessed its efficacy to identify residual tumor after enucleation using electrocautery. RESULTS: Strong correlations of fluorescence were obtained at all working distance (3, 5, 7, and 10 cm), showing the robustness of fluorescence signal for the closed-field and endoscopic fluorescence imaging devices. The higher fluorescence signals were obtained in the wound bed in the closed-field fluorescence imaging device and the residual tumor could be clearly identified by fluorescence endoscopy. CONCLUSIONS: Our FGS training model may provide experience for surgeons unfamiliar with optical surgery and subsequent tissue interactions. The model seemed particularly helpful in teaching surgeons the principles of FGS.

Infrared Fluorescence-guided Surgery for Tumor and Metastatic Lymph Node Detection in Head and Neck Cancer.

In patients with head and neck cancer (HNC), surgical removal of cancerous tissue presents the best overall survival rate. However, failure to obtain negative margins during resection has remained a steady concern over the past 3 decades. The need for improved tumor removal and margin assessment presents an ongoing concern for the field. While near-infrared agents have long been used in imaging, investigation of these agents for use in HNC imaging has dramatically expanded in the past decade. Targeted tracers for use in primary and metastatic lymph node detection are of particular interest, with panitumumab-IRDye800 as a major candidate in current studies. This review aims to provide an overview of intraoperative near-infrared fluorescence-guided surgery techniques used in the clinical detection of malignant tissue and sentinel lymph nodes in HNC, highlighting current applications, limitations, and future directions for use of this technology within the field. Keywords: Molecular Imaging-Cancer, Fluorescence © RSNA, 2024.

How far are we off? Analyzing the accuracy of surgical margin relocation in the head and neck.

BACKGROUND: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. METHODS: Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). RESULTS: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. CONCLUSIONS: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.

Comparative Outcomes for Microvascular Free Flap Monitoring Outside the Intensive Care Unit.

OBJECTIVE: There is a trend towards nonintensive care unit (ICU) or specialty ward management of select patients. Here, we examine postoperative outcomes for patients transferred to a general ward following microvascular free flap (FF) reconstruction of the head and neck. STUDY DESIGN: Retrospective quality control study. SETTING: Single tertiary care center. METHODS: Consecutive patients who underwent FF of the head and neck before and after a change in protocol from immediate postoperative monitoring in the ICU ("Pre-protocol") to the general ward setting ("Post-protocol"). Outcomes included overall length of stay (LOS), ICU LOS, FF compromise, and postoperative complications. RESULTS: A total of 150 patients were included, 70 in the pre-protocol group and 80 in the post-protocol group. There were no significant differences in age, sex, comorbidities, tumor stage, or type of FF. Mean LOS decreased from 8.18 to 7.68 days (P = .4), and mean ICU LOS decreased significantly from 5.2 to 1.7 days (P < .01). There were no significant differences in postoperative or airway-related complications (P = .6) or FF failure rate (2.9% vs 2.6%, P > .9). There was a non-significant increase in ancillary consults in the post-protocol group (45% vs 33%, P = .13) and a significant increase in rapid response team calls, a nurse-driven safety net for abnormal vitals or mental status (19% vs 3%, P = .003). CONCLUSION: We show the successful implementation of a protocol shifting care of FF patients from the ICU to a general ward postoperatively, suggesting management on the floor with less frequent flap monitoring is safe and conserves ICU beds. Additional teaching and familiarity with these patients may over time reduce the rapid response calls.

Efficacy of depatuxizumab mafodotin (ABT-414) in preclinical models of head and neck cancer.

Epidermal growth factor receptor (EGFR) is highly expressed in 80-90% of head and neck squamous cell carcinomas (HNSCCs), making it an ideal target for antibody-drug conjugates. Depatuxizumab mafodotin (ABT-414), is an EGFR-targeting ADC comprised of the monoclonal antibody ABT-806 conjugated to monomethyl auristatin F, a tubulin polymerization inhibitor. This study assessed the in vivo efficacy of ABT-414 in HNSCC. The effects of ABT-414 on HNSCCs were determined using in vitro cytotoxicity assays and in vivo flank xenograft mouse models. The distribution of ABT-414 was assessed ex vivo via optical imaging methods using a conjugate of ABT-414 to the near-infrared agent IRDye800. In vitro treatment of high EGFR-expressing human HNSCC cell lines (UMSCC47 and FaDu) with ABT-414 (0-3.38 nM) resulted in dose-dependent cell death (IC50 values of 0.213 nM and 0.167 nM, respectively). ABT-414 treatment of the FaDu mouse xenografts displayed antitumor activity (P = 0.023) without a change in body mass (P = 0.1335), whereas treatment of UMSCC47 did not generate a significant response (P = 0.1761). Fluorescence imaging revealed ABT-414-IRDye800 accumulation in the tumors of both FaDu and UMSCC47 cell lines, with a signal-to-background ratio of >10. ABT-414 treatment yielded antitumor activity in FaDu tumors, but not in UMSCC47, highlighting the potential for ABT-414 efficacy in high EGFR-expressing tumors. Although ABT-414-IRDye800 localized tumors in both cell lines, the differing antitumor responses highlight the need for further investigation into the role of the tumor microenvironment in drug delivery.

Virtual 3D Specimen Mapping in Head & Neck Oncologic Surgery.

OBJECTIVES: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post-operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. METHODS: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. RESULTS: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist-surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. CONCLUSION: Post-operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:191-197, 2024.

How Often is Cancer Present in Oral Cavity Re-resections After Initial Positive Margins?

OBJECTIVE: To evaluate the rate at which carcinoma is present in the re-resection specimen following initial positive margins during head and neck cancer surgery and its impact on oncologic outcomes. STUDY DESIGN: Retrospective chart review. METHODS: A single institution retrospective chart review of patients that underwent curative-intent surgery for oral cavity cancer was performed. Final pathology reports were reviewed to identify patients with initial positive margins who underwent re-resection during the same operation. Initial positive margin was defined as severe dysplasia, carcinoma in situ (CIS), or carcinoma. Cox proportional hazards and Kaplan-Meier analyses were used to assess for associations with survival outcomes. RESULTS: Among 1873 total patients, 190 patients (10.1%) had initial positive margins and underwent re-resection during the same surgery. Additional carcinoma, CIS, or severe dysplasia was found in 29% of re-resections, and 31% of patients with initial positive margins had final positive margins. Half of the patients with a final positive margin had a positive margin at an anatomic site different than the initial positive margin that was re-resected. The median follow-up was 636 days (range 230-1537). Re-resection with cancer and final positive margin status was associated with worse overall survival (OS; p = 0.044 and p = 0.05, respectively). However, only age, T4 disease, and surgery for recurrent oral cavity cancer were independently associated with OS (p < 0.001, p = 0.005, and p = 0.001, respectively). CONCLUSIONS: Fewer than a third of oral cavity re-resections contain further malignancy, which may suggest that surgeons have difficulty relocating the site of initial positive margin. Final positive margins are often at anatomic sites different than the initial positive margin. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:717-724, 2024.

Identification of Optimal Tissue-Marking Dye Color for Pathological Evaluation in Fluorescence Imaging Using IRDye800CW.

PURPOSE: Fluorescence-guided surgery using a tumor-specific antibody-dye conjugate is useful in various cancer types. Fluorescence imaging is a valuable tool both intraoperatively and postoperatively for ex vivo imaging. The color of inks used for tumor specimens during ex vivo specimen processing in pathology is an important consideration for fluorescence imaging since the absorption/emission of the dyes may interfere with the fluorescent dye. This study assesses suitable ink colors for use specifically with IRDye800CW fluorescence imaging. PROCEDURES: Eight tissue-marking inks or dyes (TMDs) commonly used for pathological evaluation were assessed. Agarose tissue-mimicking phantoms containing Panitumumab-IRDye800CW were used as an initial model. Mean fluorescence intensity was measured at 800 nm using both Pearl Trilogy as a closed-field fluorescence imaging system and pde-neo II as an open-field fluorescence imaging system before and after TMD application. An in vivo mouse xenograft model using the human head and neck squamous cell carcinoma FaDu cell line was then used in conjunction with TMDs. RESULTS: The retained IRDye800CW fluorescence on Pearl Trilogy was as follows: yellow at 91.0 ± 4.5%, red at 90.6 ± 2.7%, orange at 88.2 ± 2.2%, violet at 56.6 ± 1.1%, lime at 40.9 ± 1.8%, green at 19.3 ± 2.8%, black at 13.3 ± 0.6%, and blue at 8.1 ± 0.2%. The retained IRDye800CW fluorescence on pde-neo II was as follows: yellow at 86.5 ± 6.4%, red at 77.0 ± 6.2%, orange at 76.9 ± 2.8%, lime at 72.5 ± 9.5%, violet at 59.7 ± 0.4%, green at 30.1 ± 6.9%, black at 17.0 ± 2.7%, and blue at 6.7 ± 1.7%. The retained IRDye800CW fluorescence in yellow and blue TMDs was 42.1 ± 14.9% and 0.2 ± 0.2%, respectively in the mouse experiment (p = 0.039). CONCLUSION: Yellow, red, and orange TMDs should be used, and blue and black TMDs should be avoided for evaluating tumor specimens through fluorescence imaging using IRDye800CW.

Impact of comorbidities on immediate post-operative complications in oral cavity free flap patients.

PURPOSE: To examine the relationship between comorbidities and the development of immediate post-operative complications in patients undergoing oral cavity composite resection (OCCR) with free flap (FF) reconstruction. MATERIALS AND METHODS: Retrospective analysis was completed on all consecutive OCCRs with FF reconstruction performed at a single quaternary care facility between 1999 and 2020. Comorbidities, immediate post-operative complications, patient demographics, and tumor characteristics were collected. Odds ratios (OR) with 95 % confidence intervals were calculated for associations between comorbidities and immediate post-operative complications. RESULTS: 320 patients who underwent OCCR with FF reconstruction were included. One hundred twenty-one (37.8 %) patients developed a post-operative complication during their initial hospital admission. The most common complications were non-pneumonia cardiopulmonary events (14.1 %), pneumonia (9.4 %), and wound infection (8.4 %). Other complications included flap compromise, bleeding, and fistula. On multivariate analysis, patients without comorbid conditions were less likely to develop a post-operative complication (OR 0.64; 0.41-0.98). Atrial fibrillation (OR 2.94; 1.17-7.39) and cerebrovascular disease (OR 2.28; 1.08-4.84) were associated with increased odds of developing any complications. Furthermore, cerebrovascular disease (OR: 2.33; 1.04-5.39) and peripheral vascular disease (OR: 2.7; 1.2-6.08) were independently associated with pneumonia. CONCLUSION: In this retrospective review of patients undergoing OCCR with FF reconstruction for oral cavity SCC, lack of identifiable comorbidities appeared to be protective for post-operative complications while atrial fibrillation and cerebrovascular disease were associated with increased odds of any complication. Pre-existing vascular disease was also associated with an increased risk of pneumonia.

Frontal and anterior temporal hypometabolism post chemoradiation in head and neck cancer: A real-world PET study.

BACKGROUND AND PURPOSE: Adverse neurological effects after cancer therapy are common, but biomarkers to diagnose, monitor, or risk stratify patients are still not validated or used clinically. An accessible imaging method, such as fluorodeoxyglucose positron emission tomography (FDG PET) of the brain, could meet this gap and serve as a biomarker for functional brain changes. We utilized FDG PET to evaluate which brain regions are most susceptible to altered glucose metabolism after chemoradiation in patients with head and neck cancer (HNCa). METHODS: Real-world FDG PET images were acquired as standard of care before and after chemoradiation for HNCa in 68 patients. Linear mixed-effects voxelwise models assessed changes after chemoradiation in cerebral glucose metabolism quantified with standardized uptake value ratio (SUVR), covarying for follow-up time and patient demographics. RESULTS: Voxelwise analysis revealed two large clusters of decreased glucose metabolism in the medial frontal and polar temporal cortices following chemoradiation, with decreases of approximately 5% SUVR after therapy. CONCLUSIONS: These findings provide evidence that standard chemoradiation for HNCa can lead to decreased neuronal glucose metabolism, contributing to literature emphasizing the vulnerability of the frontal and anterior temporal lobes, especially in HNCa, where these areas may be particularly vulnerable to indirect radiation-induced injury. FDG PET shows promise as a sensitive biomarker for assessing these changes.

Flavinated SDHA underlies the change in intrinsic optical properties of oral cancers.

The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region, with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.

EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial.

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

Flavinated SDHA Underlies the Change in Intrinsic Optical Properties of Oral Cancers.

The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lie at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.

Determination of Flap Survival Isolated From Wound Bed Vasculature Using a Murine Axial Flap Model.

Background: Axial pattern flaps are a common reconstructive option following resection of soft tissue malignancies. We determine the early dependence of an axial flap on wound bed vasculature by isolating the underlying wound bed and depriving contact with the overlying flap. Materials and Methods: Mice were divided into 5 groups: No silicone (n = 7), silicone in the proximal 50% of the wound bed (n = 8), silicone in the distal 50% of the wound bed (n = 5), silicone over the full length of the wound bed with pedicle preservation (n = 5), and silicone over the full length of the wound bed with pedicle sacrifice (n = 5). The pedicle was the lateral thoracic artery. Daily photographs were taken, and the percent of viable flap was determined using ImageJ© software (public domain JAVA image processing program, National Institute of Health, Bethesda, MA). Percent flap viability for each group was compared to the no silicone group, which acted as the reference. Results: Mean differences in percent flap necrotic area (with 95% confidence interval) compared to the no silicone group were -0.15% (-15.09 to 14.09), 2.07% (-5.26 to 9.39), 2.98% (-10.98 to 16.94), and 14.21% (0.48 to 27.94) for the full-length silicone with preserved pedicle, proximal silicone, distal silicone, and full-length silicone with sacrificed pedicle groups, respectively. The full-length silicone with sacrificed pedicle group had a significant difference in flap viability (P = .045) compared to the no silicone group. Conclusion: We investigate the role of the wound bed vasculature in a murine axial flap model and demonstrate that the wound bed vasculature is not essential for early distal flap survival.

Augmented-Reality Surgery to Guide Head and Neck Cancer Re-resection: A Feasibility and Accuracy Study.

BACKGROUND: Given the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections. METHODS: This study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded. RESULTS: The 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1-15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2-43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01). CONCLUSIONS: This cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.

Intraoperative molecular imaging: 3rd biennial clinical trials update.

Significance: This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery. Aim: National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed. Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's third clinical trials update on IMI were selected to discuss their clinical trials and endpoints. Results: Dyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed. Conclusions: IMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.