Optical Imaging of Head and Neck Cancer

• Sponsor: Sharmila Anandasabapathy, MD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01456143
• Collaborator: William Marsh Rice University (Other)
• Enrollment: 33
• Location: 1
• Arm: 1
• Duration (Months): 31
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study examines if certain imaging techniques and devices can aid the surgeon in detecting cancer during the surgical procedure.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma; Neoplasia; Head and Neck Cancer	Device: High Resolution Microendoscopy (HRME); Other: Proflavine hemisulfate	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: In Vivo Multimodal Imaging of Upper Aerodigestive Epithelia
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: HRME with proflavine 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); 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.; Other Names: HRME ; Other: Proflavine hemisulfate; 0.01% Proflavine hemisulfate used as a fluorescent contrast agent applied topically to mucosa; Other Names: Proflavine

Outcome Measures

Primary Outcome Measures

1. Accuracy [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   Accuracy of reviewers in differentiating neoplastic or benign mucosa in comparison to the pathology results

2. Sensitivity [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   Sensitivity = probability that the HRME correctly classifies as positive those with neoplasia compared to pathology results

3. Specificity [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   Specificity = Probability that the HRME correctly classifies as negative those without neoplasia compared to pathology results

4. Positive Predictive Value [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   PPV = proportion of those with a positive test who have neoplasia compared to pathology results

5. Negative Predictive Value [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   NPV = proportion of those with a negative test without neoplasia compared to pathology results

6. Interrater Reliability [Immediately following image (day of enrollment or up to 2 weeks after enrollment)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10017

Sponsors and Collaborators

• Sharmila Anandasabapathy, MD
• William Marsh Rice University

Investigators

• Principal Investigator: Andrew Sikora, MD, PhD, Icahn School of Medicine at Mount Sinai
• Principal Investigator: Sharmila Anandasabapathy, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sharmila Anandasabapathy, MD, Principal Investigator, Anandasabapathy, Sharmila, M.D.
• ClinicalTrials.gov Identifier: NCT01456143
• Other Study ID Numbers: GCO 09-2057
• First Posted: Oct 20, 2011
• Last Update Posted: Feb 1, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sharmila Anandasabapathy, MD, Principal Investigator, Anandasabapathy, Sharmila, M.D.: Squamous Cell Carcinoma; Neoplasia; Optical imaging; Head and Neck Cancer; Oropharynx; Larynx; Oral Cavity
• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Neoplasms; Proflavine

Study Results

Participant Flow

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	33
COMPLETED	33
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	HRME With Proflavine Hemisulfate
Arm/Group Description	High Resolution Microendoscopy imaging device used in conjunction with proflavine hemisulfate as a contrast agent
Overall Participants	33
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.09 (12.47)
Sex: Female, Male (Count of Participants)
Female	14 42.4%
Male	19 57.6%
Region of Enrollment (participants) [Number]
United States	33 100%

Outcome Measures

1. Primary Outcome

Title	Accuracy
Description	Accuracy of reviewers in differentiating neoplastic or benign mucosa in comparison to the pathology results
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Mean (95% Confidence Interval) [Percent of images with correct diagnosis]	95.1

2. Primary Outcome

Title	Sensitivity
Description	Sensitivity = probability that the HRME correctly classifies as positive those with neoplasia compared to pathology results
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Mean (95% Confidence Interval) [Percent of images with correct diagnosis]	96

3. Primary Outcome

Title	Specificity
Description	Specificity = Probability that the HRME correctly classifies as negative those without neoplasia compared to pathology results
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Mean (95% Confidence Interval) [Percent of images with correct diagnosis]	95

4. Primary Outcome

Title	Positive Predictive Value
Description	PPV = proportion of those with a positive test who have neoplasia compared to pathology results
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Mean (95% Confidence Interval) [Percent of images with correct diagnosis]	91

5. Primary Outcome

Title	Negative Predictive Value
Description	NPV = proportion of those with a negative test without neoplasia compared to pathology results
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Mean (95% Confidence Interval) [Percent of images with correct diagnosis]	98

6. Primary Outcome

Title	Interrater Reliability
Description	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.
Time Frame	Immediately following image (day of enrollment or up to 2 weeks after enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HRME With Proflavine
Arm/Group Description	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.
Measure Participants	33
Number (95% Confidence Interval) [proportion of agreement among 11 experts]	.81

Adverse Events

Time Frame	(day of enrollment or up to 2 weeks after enrollment)]
Adverse Event Reporting Description	Serious and other adverse events were monitored and assessed, but none were observed
Arm/Group Title	HRME With Proflavine Hemisulfate
Arm/Group Description	High Resolution Microendoscopy imaging device used in conjunction with proflavine hemisulfate as a contrast agent
All Cause Mortality
	HRME With Proflavine Hemisulfate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	HRME With Proflavine Hemisulfate
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Other (Not Including Serious) Adverse Events
	HRME With Proflavine Hemisulfate
	Affected / at Risk (%)	# Events
Total	0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.