A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent (original) (raw)

Role of near-infrared fluorescence imaging in head and neck cancer surgery: from animal models to humans

Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde

Complete resection of head and neck cancers with negative surgical margins improves the prognosis of the disease and decreases the recurrence rate. Near-infrared fluorescence-guided surgery of head and neck cancer is a rapidly evolving field that represents an invaluable tool for tumor detection and resection. Here, we present a literature review of the principles of near-infrared fluorescence imaging and its use in head and neck cancer surgery. We discuss important studies in both animal models and humans that have been carried out up to this point. We also outline the important fluorescent molecules and devices used in head and neck fluorescence imaging-guided surgery. Although near-infrared fluorescence-guided surgery for head and neck cancers showed efficacy in animal models, its use in humans is limited by the small number of fluorescent probes that are approved for clinical use. However, it is considered as a novel surgical aid that helps delineate tumor margins preoperatively...

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery

Journal of surgical oncology, 2015

Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n = 11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. During open-field ima...

A feasibility study of NIR fluorescent image-guided surgery in head and neck cancer based on the assessment of optimum surgical time as revealed through dynamic imaging

OncoTargets and Therapy, 2013

Background: In order to minimize surgical stress and preserve organs, endoscopic or robotic surgery is often performed when conducting head and neck surgery. However, it is impossible to physically touch tumors or to observe diffusely invaded deep organs through the procedure of endoscopic or robotic surgery. In order to visualize and safely resect tumors even in these cases, we propose using an indocyanine green (ICG) fluorescence method for navigation surgery in head and neck cancer. Objective: To determine the optimum surgical time for tumor resection after the administration of ICG based on the investigation of dynamic ICG fluorescence imaging. Methods: Nine patients underwent dynamic ICG fluorescence imaging for 360 minutes, assessing tumor visibility at 10, 30, 60, 120, 180, and 360 minutes. All cases were scored according to near-infrared (NIR) fluorescence imaging visibility scored from 0 to 5. Results: Dynamic NIR fluorescence imaging under the HyperEye Medical System indicated that the greatest contrast in fluorescent images between tumor and normal tissue could be observed from 30 minutes to 1 hour after the administration of ICG. The optimum surgical time was determined to be between 30 minutes to 2 hours after ICG injection. These findings are particularly useful for detection and safe resection of tumors invading the parapharyngeal space. Conclusion: ICG fluorescence imaging is effective for the detection of head and neck cancer. Preliminary findings suggest that the optimum timing for surgery is from 30 minutes to 2 hours after the ICG injection.

Detection of surgical margins in oral cavity cancer

Current Opinion in Otolaryngology & Head and Neck Surgery

Purpose of review-The quantity of tissue removed during an oncologic surgical procedure is not standardized and there are numerous reports of local recurrence despite histologically adequate resection margins. The oral cavity is one of the sites in the head and neck with high chances of recurrence following negative margins. To address this need, this article reviews the recent applications of Dynamic Optical Contrast Imaging (DOCI) towards both oral screening and the intraoperative evaluation of tumor margins in head and neck surgery. Recent findings-Human ex vivo and in vivo trials suggest DOCI is safe, low cost, and sensitive for differentiating cancerous from normal tissues throughout the head and neck, in addition to the oral cavity. Ex vivo imaging of OSCC specimens generated histologically-verified image contrast. Furthermore, in vivo intraoperative results demonstrate significant potential for image-guided detection and resection of oral cavity squamous cell carcinoma (OSCC). Summary-DOCI augments tissue contrast and may enable surgeons to: clinically screen patients for oral cancer, make histologic evaluations in vivo with fewer unnecessary biopsies, delineate clinical margins for tumor resection, provide guidance in the choice of biopsy sites, and preserve healthy tissue to increase the postoperative functionality and quality of life of the patient.

Image guided surgery in the management of head and neck cancer

Oral Oncology, 2016

Complete resection of head and neck tumors relies on palpation and visual inspection. Achieving a negative margin in remote locations in the head and neck region, especially in close proximity to critical structures, is often difficult to achieve. Positive resection margins in head and neck cancer are at high risk to develop recurrent disease and associated with poor prognosis. Near-infrared fluorescence-guided optical imaging is an emerging technology with the potential to move the surgical field forward and facilitate surgeons to visualize tumors in real-time intra-operatively. In this review, our focus is to discuss the recent advances and the potential application of near infrared (NIR) fluorescent-guided surgery in the management of head and neck cancer.

Characterizing the utilities and limitations of repurposing an open-field optical imaging device for fluorescence-guided surgery in head and neck cancer patients

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2016

To assess the potential of US Food and Drug Administration cleared devices designed for indocyanine green-based perfusion imaging to identify cancer-specific bioconjugates with overlapping excitation and emission wavelengths. Recent clinical trials have demonstrated potential for fluorescence-guided surgery, but the time and cost of the approval process may impede clinical translation. To expedite this translation, we explored the feasibility of repurposing existing optical imaging devices for fluorescence-guided surgery. Consenting patients (n = 15) scheduled for curative resection were enrolled in a clinical trial evaluating the safety and specificity of cetuximab-IRDye800 (NCT01987375). Open-field fluorescence imaging was performed pre-operatively and during the surgical resection. Fluorescence intensity was quantified using integrated instrument software, and the tumor-to-background ratio (TBR) characterized fluorescence contrast. In the pre-operative clinic, the open-field devi...

Use of Panitumumab-IRDye800 to Image Microscopic Head and Neck Cancer in an Orthotopic Surgical Model

Annals of Surgical Oncology, 2012

Background-Fluorescence imaging hardware (SPY) has recently been developed for intraoperative assessment of blood flow via detection of probes emitting in the near-infrared (NIR) spectrum. This study sought to determine if this imaging system was capable of detecting micrometastatic head and neck squamous cell carcinoma (HNSCC) in preclinical models. Methods-A NIR fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody targeting EGFR (panitumumab) or non-specific IgG. HNSCC flank (SCC-1) and orthotopic (FADU and OSC19) xenografts were imaged 48-96hrs following systemic injection of labeled panitumumab or IgG. The primary tumor and regional lymph nodes were dissected using fluorescence guidance with the SPY system and grossly assessed with a charge-coupled NIR system (Pearl). Histologic slides were also imaged with a NIR charged-coupled device (Odyssey) and fluorescence intensity was correlated with pathologic confirmation of disease. Results-Orthotopic tongue tumors were clearly delineated from normal tissue with tumor-tobackground ratios of 2.9(Pearl) and 2.3(SPY). Disease detection was significantly improved with panitumumab-IRDye compared to IgG-IRDye800 (P<0.05). Tissue biopsies (average size=3.7mm) positive for fluorescence were confirmed for pathologic disease by histology and immunohistochemistry (n=25/25). Biopsies of non-fluorescent tissue were proven to be negative for malignancy (n=28/28). The SPY was able to detect regional lymph node metastasis (<1.0mm) and microscopic areas of disease. Standard histological assessment in both frozen and paraffinembedded histologic specimens was augmented using the Odyssey. Conclusions-Panitumumab-IRDye800 may have clinical utility in detection and removal of microscopic HNSCC using existing intraoperative optical imaging hardware and may augment analysis of frozen and permanent pathology.

Analysis of the Surgical Margins of the Oral Cancer using in Situ and Ex Vivo Fluorescence Spectroscopy

ARC Journal of Surgery, 2016

Fluorescence spectroscopy (FS) has been studied for the early detection and classification of tissues alterations of the oral mucosa. In the present non-randomized prospective trial we investigate tissue changes using FS, at 532 nm excitation, in oral cancer in situ and immediate ex vivo resected specimen with particular attention to the surgical margins. A total of 22 patients with OSCC and 20 volunteers with normal mucosa were submitted to analysis system of FS in the exam of the subjects mucosal with oral cancer (lesions and surgical margins) and health volunteers (in several oral sites). In lesions and surgical margins the examination was carried out in situ and ex vivo. All analyzes were correlated with the pathological diagnosis. In all patients with OSCC, we observed differences in the spectra of the border of the lesions versus surgical margins versus normal mucosa, these degree of similarity was calculated by anatomic site. The degree of similarity ranged from 15 to 50 percent depending on the anatomical site and healthy or altered mucosa, and followed the same pattern between different individuals. Differences were also observed in the moments in situ and ex vivo from the same patient. There is in all patients with OSCC distinct behaviors regarding the form and intensity considering different oral sites showed in FS, and we saw the usefulness of FS to discriminate tissue changes in surgical margins.