Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Barrett Esophagus

Hyperplasia

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

VLE (Volumetric laser endomicroscopy) performed alone, followed by IRIS (Intelligent real-time image segmentation) imaging.

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging, followed by VLE alone.

IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

IRIS (Intelligent real-time image segmentation)

VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE (Volumetric laser endomicroscopy)

Arvind Trindade, MD

This is a prospective randomized clinical trial examining how IRIS (Intelligent Real-time Image Segmentation) affects biopsy patterns in VLE (Volumetric laser endomicroscopy).

Patients will undergo a VLE exam with and without IRIS per the standard of care. All patients regardless of the study participation in this study would receive VLE with and without IRIS clinically. They will be randomized into VLE without IRIS first vs VLE with IRIS first. The BUDDY Randomization System, provided for use by the Northwell Health Biostatistics Unit, will be used for this. Randomization will be stratified based on prior diagnosis of dysplasia. The order in which the patient is randomized to will be recorded on the case report form. There will be concealed allocation as the study coordinator performing the randomization will not know the order of the next allocation.

Both VLE and IRIS imaging are being performed as standard of care. However, randomization of the order allows for comparison of the two. Regions of interest (ROI) will be recorded using a full scan and recorded on the case report form. The time to identification of ROIs will also be recorded. Each group will then cross over such that the VLE without IRIS group will then have IRIS turned on. ROI will then be recorded for each group based on full scans. A consensus ROI will be recorded based on the two exams. Only one ROI per centimeter will be allowed to avoid overlapping of laser marks. In addition, VLE without IRIS and IRIS marks within 75 frames of each other or 2 hours (on a clock face orientation) will be considered the same target.

Laser marking will then be performed. A double laser mark will be applied to all IRIS ROIs. A single laser mark will be applied to VLE ROIs. Targeted biopsies will be taken of all laser marks and placed in separate biopsy jars. Biopsies will be taken in between the laser marks for double laser marked areas. For single laser marks, biopsies will be taken on either side of the laser mark. Resection of visible lesions will then occur per standard of care (if present) followed by random biopsies of the segment. Random biopsies are pinch biopsies every 1 cm the length of the Barrett's in a 4 quadrant fashion per gastrointestinal society guidelines. There are no additional research biopsies being performed outside this study. The targeted biopsies are based on the VLE features that are suspicious for dysplasia and thus standard of care. The other biopsies being performed here are random biopsies which are also being performed for standard of care. Biopsied samples will be stored per standard of care procedures per the pathology department. They will not be stored for future research purposes.

Following each procedure, the physician will be asked a series of Likert Scale questions to assess the utility of IRIS in that procedure, including how it impacts their confidence in image interpretation, their ability to assimilate data more easily and quickly, and their overall perception of the technology.

Although, the VLE with IRIS and VLE without IRIS are being performed as standard of care, all adverse events will be recorded and reported to the IRB.

All data will be entered into a central encrypted REDCap database.

Expert pathologists who specialize in gastrointestinal pathology will read the histology. A second gastrointestinal pathologist will confirm any histologic diagnosis of dysplasia. This is the standard of care at Northwell Health and academic medical centers per gastrointestinal society guidelines.

All procedures (upper endoscopy, volumetric laser endomicroscopy, and IRIS enhanced VLE) will be performed as standard of care. The prospective data collection and initial randomization will be the research component. All data collected will be de-identified before being transferred into a database. This will be kept in a safe place that is only accessible to the research team.

Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)

Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS): a Multi-center Randomized Prospective Study

The length of time required to fully assess and interpret the results of a VLE scan. Time will be a surrogate for ease of interpretation. Time will be recorded from start of image interpretation to the end of image interpretation. Length of the Barrett's segment will be taken into account (time per cm of Barrett's) when comparing this outcome between patients and procedures.

The length of time required to fully assess and interpret the results of a VLE scan. Time will be a surrogate for ease of interpretation. Time will be recorded from start of image interpretation to the end of image interpretation. Length of Barrett's will be taken into account (time per cm of Barrett's) when comparing this outcome between patients and procedures.

Biopsy yield (in terms of dysplasia present versus not present) of subjects with IRIS biopsies (double laser mark) will be compared to subjects with VLE without IRIS biopsies (single laser mark) and subjects with random biopsies (taken every 1cm in a four quadrant fashion throughout the length of the Barrett's).

NinePoint Medical

Mayo Clinic

Northwell Health

VLE (Volumetric laser endomicroscopy) performed alone, followed by IRIS (Intelligent real-time image segmentation) imaging.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE Without IRIS

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging, followed by VLE alone.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE With IRIS

VLE Without IRIS, Followed by VLE With IRIS

VLE With IRIS, Followed by VLE Without IRIS

Total

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

By utilizing expert users, we're unable to assess the impact of IRIS on novice interpretation. We also utilized a surveillance biopsy protocol that avoided areas of laser marking to avoid confounding and were thus unable to compare VLE-related dysplasia detection to that which would have occurred in the standardized biopsy protocol. Finally, although we did randomize the order of interpretation, it is not possible to eliminate all bias from a subjective interpretation paradigm.

Dr. Arvind Trindade

Total interpretation time (VLE/IRIS)

Interpretation time (VLE alone)

First Interpretation Time

Second Interpretation Time

Time for Image Interpretation (Mean)

Scaled First Interpretation Time

Scaled Second Interpretation Time

Time for Image Interpretation (Mean - Scaled)

Time for Image Interpretation (Median - Scaled)

VLE (Volumetric laser endomicroscopy) performed alone,

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

VLE (Volumetric laser endomicroscopy) performed with IRIS (Intelligent real-time image segmentation) imaging.

VLE (Volumetric laser endomicroscopy): VLE uses infrared light to produce real time high-resolution cross sectional imaging of the esophagus.

IRIS (Intelligent real-time image segmentation): IRIS has the ability to identify and display three specific images features that may correlate with dysplasia that are represented in different color schemes.

Standardized method of biopsy collection entailing taking biopsies every 1cm of the Barrett's segment in a 4 quadrant fashion, the current standard of care.

Seattle Protocol

Subjects With Dysplasia on Biopsies

Overall Study

Ear, Nose, and Throat Diseases

Rare Diseases

Esophageal Neoplasms

Adenocarcinoma

Gastroesophageal Reflux

Esophagitis

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Esophageal Motility Disorders

Esophageal Spasm, Diffuse

Deglutition Disorders

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastroenteritis

Esophageal Cancer

Individuals who underwent endoscopy and were found to only have one of the following:

* Esophageal adenocarcinoma of any stage
* Esophageal adenocarcinoma confined to the mucosa (stage Tis)

Individuals who underwent endoscopy and were found to only have one of the following:

* Barrett's Esophagus, with high-grade dysplasia, independently of Barrett's segment length
* Esophageal adenocarcinoma of any stage
* Esophageal adenocarcinoma confined to the mucosa (stage Tis)

Individuals who underwent endoscopy and were found to only have Barrett's Esophagus, with one of the following:

* Craniocaudal maximal extension of 3 cm or more
* Low-grade dysplasia at most, independently of Barrett's segment length

Individuals who underwent endoscopy and were found not to have any Barrett's Esophagus or adenocarcinoma.

A panel of circulating microRNA, whose expression level is tested in cell-free derived samples.

EMERALD (Esophageal MicroRNAs for BaRRett's esophagus, Adenocarcinoma, and Dysplasia)

Ajay Goel, PhD

This study aims to develop a highly sensitive, specific, and cost-effective blood assay for the early detection of esophageal adenocarcinoma and its precursor lesions, using advanced machine learning and state-of-the-art biological analyses.

Esophageal adenocarcinoma (EAC) is a significant global health concern, ranking second in lethality (after pancreatic cancer). Despite being potentially preventable, it remains a leading cause of cancer-related deaths. Traditional screening methods have relied on an endoscopy-first approach to screen for the precursor of EAC, which is Barrett's esophagus (BE). After BE detection, BE is then regularly surveiled to monitor the development of dysplasia, which can be treated to prevent malignant transformation. An endoscopy-first approach is sensitive BE and, therefore, it lowers the risk of developing EAC but it also faces challenges such as invasiveness, cost, and patient compliance.

Non-invasive tests are more appealing to patients than invasive tests and can increase participation rates. Biomarker studies have shown promise, but existing tests lack sensitivity for early-stage EAC and, most importantly, to its precursor lesion BE. This is likely because they over-sampled analytes that are primarily expressed at the EAC end of the spectrum, but not in BE yet during the BE to EAC sequence.

This study proposes developing an innovative liquid biopsy test tailored for EAC and BE to address this. An ideal screening test should be minimally invasive, highly sensitive, and cost-effective. This test would optimize patient compliance and resource allocation by detecting both conditions from a single blood draw. More specifically, circulating microRNA (miRNA) analysis shows promise: tests based on cell-free microRNA (cf-miRNA) have demonstrated high sensitivity.

This study will develop a non-invasive blood test for BE and EAC in four phases:

1. In silico genome-wide profiling of tissue miRNA to select the best candidates for biomarker panels.
2. Prioritization of the biomarkers that are differentially expressed across the entire continuum of BE to EAC sequence, compared to the normal mucosa
3. Transition of these biomarkers to a liquid biopsy assay, confirming their detectability in blood as well as their differential expression in cases compared to controls
4. Utilizing machine learning to identify the most promising candidates and train algorithms for detecting EAC and BE, based on results from quantitative polymerase chain reaction (qPCR) analysis.
5. Independently validating these signatures using diverse cohorts to ensure broad applicability and compare the effectiveness of the blood assay to standard care through retrospective and prospective studies.

This study aims to develop a highly sensitive, specific, and cost-effective liquid biopsy for early detection of BE and EAC. Success could transform clinical practice by preventing EAC through early detection of pre-malignant lesions. Innovations include incorporating pre-malignant lesions into screening. This approach could potentially reduce EAC mortality and incidence and pave the way for new clinical trials.

A Liquid Biopsy for High-risk Pre-cancer Screening of Esophageal Adenocarcinoma

A Liquid Biopsy to Screen for Barrett's Esophagus, Dysplasia, and Esophageal Adenocarcinoma: the EMERALD Multi-center Study.

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

True negative rate: the probability of a negative test result, conditioned on the individual truly being negative

A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)	NCT03814824	Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph...	IRIS (Intellige... VLE (Volumetric...	18 Years -	Northwell Health
Volumetric Laser Endomicroscopy With Intelligent Real-time Image Segmentation (IRIS)	NCT03814824	Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph... Barrett's Esoph...	IRIS (Intellige... VLE (Volumetric...	18 Years -	Northwell Health
A Liquid Biopsy for High-risk Pre-cancer Screening of Esophageal Adenocarcinoma	NCT06381583	Esophagus Cance... Esophageal Canc... Esophageal Canc... Esophageal Neop... Esophagus Adeno... Esophagus, Barr... Barrett Esophag... Barrett Adenoca... Barrett Epithel... Barretts Esopha... Barrett's Esoph... Barretts Esopha... Barretts Esopha... Barrett Esophag... Barrett's Esoph... Barrett's Esoph... Gastroesophagea... Reflux Disease Esophageal Aden... Esophageal Dysp... Esophageal Neop...	EMERALD (Esopha...	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for barrett's esophagus with dysplasia, unspecified