Title : Methylation based biomarker test in combination with non-invasive cell collection device for detection of barrett's esophagus and esophageal adenocarcinoma
Abstract:
Barrett esophagus (BE) is a pre-malignant condition characterized by the conversion of the normal esophageal squamous epithelium into metaplastic columnar epithelium. BE is the only known precursor lesion of esophageal adenocarcinoma (EAC), a cancer with high mortality rate (80% or more) and rapidly increasing incidence rate in the United States and other Western countries. American College of Gastroenterology (ACG) guidelines recommend screening endoscopy for patients with chronic gastroesophageal reflux disease (GERD) and additional risk factors, however compliance to the program has been poor due to invasive nature of Endoscopy. A non-invasive screening assay to test patients with symptoms of GERD for BE can improve compliance to the program and can lead to overall reduction in mortality due to EAC. EsoCheck is FDA cleared non-invasive balloon cell collection device (K183262) that is designed to sample cells from a targeted region of the esophagus in a five-minute office-based procedure, without the need for endoscopy, followed by a methylation biomarker-based testing using EsoGuard assay, a Laboratory Developed Test (LDT). EsoGuard assay is College of American Pathology (CAP)/ Clinical Laboratory Improvement Amendments (CLIA) approved test that detects methylation changes in two biomarker genes (Vimentin and CCNA1) in distal esophageal cells collected using EsoCheck device. EsoCheck device is a vitamin pill-sized capsule containing a small inflatable balloon attached to a thin catheter. As the catheter is withdrawn, it swabs the target area for a sample of cells and protects that sample from contamination as the device is removed. Post collection, the balloon samples is detached from catheter using scissors and samples are transported in a fixative at room temperature. DNA is extracted from samples and tested using EsoGuard assay. EsoGuard assay is a semi-quantitative two gene methylation biomarker based next generation sequencing (NGS) assay for detection of complete spectrum of conditions from BE to EAC including non-dysplastic and dysplastic BE, and Short Segment and Long Segment BE. Sensitivity of EsoGuard assay for detection of combined BE and EAC is 88.0% (n=50) while specificity of the assay is 91.7% (n=36). Analytical accuracy of EsoGuard assay is >90%. Overall, combined system of EsoGuard assay with EsoCheck cell collection device provide a highly accurate method for detection of BE and EAC and can be used as an aid to stratify GERD patients for confirmatory endoscopy. Recent ACG guideline (March 2022) have acknowledged non-invasive swallowable device in combination with biomarker testing as an alternative to endoscopy for screening of BE in patients with chronic reflux symptoms and other risk factors.
