Optical Imaging of Head and Neck Cancer

Study Overview
=================
Brief Summary
-----------------
This study examines if certain imaging techniques and devices can aid the surgeon in detecting cancer during the surgical procedure.

Detailed Description
-----------------
The purpose of this study is to determine if optical imaging modalities used at the time of surgical resection for head and neck squamous cell carcinoma can help delineate normal from cancerous mucosa. The High resolution microendoscope, developed by our collaborators at Rice university, can allow for real time visualization of tissue nuclei. The overall aim of this study is to determine if this device can be used to enhance the accuracy of intraoperative margin detection during tumor resection for head and neck cancer. At the time of tumor resection for head and neck squamous cell carcinoma, a wide field imaging device will be used to identify suspicious areas. The High resolution device will then image representative areas from the tumor, the tumor margin, and normal mucosa. A topical dye, proflavin, will be placed on the tissue to enhance the visualization of nuclei prior to imaging with the HRME device. Following imaging, biopsies of the imaged areas will be taken and submitted for pathology diagnosis. The images of the biopsies will then be compared and the device will be evaluated for accuracy of margin detection at the time of tumor resection.

Official Title
-----------------
In Vivo Multimodal Imaging of Upper Aerodigestive Epithelia

Conditions
-----------------
Squamous Cell Carcinoma, Neoplasia, Head and Neck Cancer

Intervention / Treatment
-----------------
* Device: High Resolution Microendoscopy (HRME)
* Other: Proflavine hemisulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Biopsy Proven Squamous Cell Carcinoma of the oral cavity, oropharynx, larynx, hypopharynx Must be receiving surgical treatment for their cancer Exclusion Criteria: Presence of medical or psychiatric condition affecting the ability to give informed consent Known allergy to Proflavin Pregnant or nursing Females

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRME with proflavine<br>High Resolution Microendoscopy (HRME) imaging device that operates as a fluorescence microscope with a fiber optic imaging probe. The probe is placed against the mucosa to obtain images relayed to a tablet computer. 0.01% Proflavine hemisulfate used as a fluorescent contrast agent applied topically to mucosa. HRME is used to capture images of suspicious areas sprayed with proflavine hemisulfate. | Device: High Resolution Microendoscopy (HRME)<br>* High Resolution Microendoscopy imaging device that operates as a fluorescence microscope with a fiber optic imaging probe. The probe is placed against the mucosa to obtain images relayed to a tablet computer.<br>* Other names: HRME;Other: Proflavine hemisulfate<br>* 0.01% Proflavine hemisulfate used as a fluorescent contrast agent applied topically to mucosa<br>* Other names: Proflavine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy | Accuracy of reviewers in differentiating neoplastic or benign mucosa in comparison to the pathology results | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 
| Sensitivity | Sensitivity = probability that the HRME correctly classifies as positive those with neoplasia compared to pathology results | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 
| Specificity | Specificity = Probability that the HRME correctly classifies as negative those without neoplasia compared to pathology results | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 
| Positive Predictive Value | PPV = proportion of those with a positive test who have neoplasia compared to pathology results | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 
| Negative Predictive Value | NPV = proportion of those with a negative test without neoplasia compared to pathology results | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 
| Interrater Reliability | Amount of agreement among the 11 blinded head and neck cancer specialists, determined by the Fleiss Kappa. 33 benign and 65 cancer images were evaluated by the reviewers who were blinded to the anatomical site, tumor subsite, and final histopathologic diagnosis. Each reviewer was asked to classify each image as benign or neoplastic. The reviewers evaluated the images based on nuclear size, nuclear to cytoplasmic ratio, and overall cell architecture. Images were randomized in their presentation to the reviewers as to not establish any pattern. Each reviewer provided their interpretation in isolated settings to avoid influence from other reviewers. | Immediately following image (day of enrollment or up to 2 weeks after enrollment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Squamous Cell Carcinoma, Neoplasia, Optical imaging, Head and Neck Cancer, Oropharynx, Larynx, Oral Cavity