Barrett's esophagus (BE), a metaplastic change of the esophageal lining associated with chronic gastroesophageal reflux disease, is the only known precursor to esophageal adenocarcinoma (EAC). EAC is one of the most rapidly increasing cancers in the United States, frequently presenting at an advanced stage and associated with a dismal 5-year survival rate. Endoscopic eradication therapy (EET) is the standard of care for patients with BE and high-grade dysplasia (HGD) or mucosal EAC. However, a central unresolved issue is whether BE patients with low-grade dysplasia (LGD) benefit from EET. The diagnosis of LGD is far more common than HGD and is associated with a lower risk of EAC, so it is unclear whether the costs and complications of EET are justified in this group of patients. The presence of clinical equipoise and the importance of this question indicates that a trial of endoscopic surveillance versus EET in this patient population is an urgent, unmet gap in our current knowledge regarding treatment of this common condition.
We aim to address this knowledge gap in a two-step process. Step 1 is a one year U34 planning grant during which we aim to develop the necessary study infrastructure, research protocols and documents in close collaboration with the NIDDK. Step 2 is a five year U01 multicenter randomized controlled trial to compare EET and endoscopic surveillance for the management of LGD.
Specific Aim #1 will compare the two approaches using the primary endpoint of neoplastic progression rate (progression to HGD or mucosal or invasive EAC).
Specific Aim #2 will compare defined patient-centered outcomes such as health-related quality of life between the two treatment groups.
Specific Aim #3 will compare the performance of molecular (TissueCypher and p53 immunohistochemistry) and imaging (wide-area transepithelial sampling ? WATS) biomarkers to conventional histologic assessment of dysplasia via forceps biopsy to improve risk-stratification in BE with LGD patients. Biological samples will also be obtained at study enrollment and during follow-up from all enrolled subjects to establish a biorepository for future translational research initiatives. The relevance of this work to the public health is high. BE is a common condition affecting 2-3% of adult US population and LGD is seen in up to 40% of BE patients. This is a precursor for EAC, a cancer that has increased in incidence over the past four decades. Millions of dollars are spent yearly on the management of patients with BE and EAC. The impact of our innovative study will include identifying the best patient-centered treatment approach for BE patients with LGD, which will inform the care of thousands of patients annually.
? Public Health Relevance Thousands of patients with Barrett's esophagus (a change in the inner lining of the esophagus due to chronic acid reflux disease) are diagnosed with low-grade dysplasia, a precancerous condition which is the ?first step? towards esophageal cancer (a lethal cancer that has increased in incidence over the last five decades), and has a low, but real, risk of progression to cancer. Endoscopic treatments are available to destroy low-grade dysplasia, with a return of the normal inner lining, but these treatments are costly and associated with complications. Whether patients who develop low-grade dysplasia should undergo these endoscopic treatments, or instead undergo periodic endoscopic surveillance procedures (endoscopic examination and obtaining biopsies), reserving the endoscopic treatments for only those who develop either high-grade dysplasia or cancer, is a significant knowledge gap that will be addressed by comparing the effectiveness of these two approaches fundamentally changing the way we manage patients with Barrett's esophagus.
