A Multicenter Randomized Controlled Trial of Surveillance versus. Endoscopic Therapy for Barretts Esophagus with Low-grade Dysplasia: The SURVENT Trial

项目概要/摘要 Barrett食管（BE）是一种与慢性食管炎相关的食管内膜化生性改变， 胃食管反流病是唯一已知的食管腺癌（EAC）的前兆。EAC是 在美国增长最快的癌症之一，经常出现在晚期 而且5年存活率很低内镜根除治疗（EET）是标准的 BE和高度异型增生（HGD）或粘膜EAC患者的护理。然而，一个未解决的中央 问题是患有低度异型增生（LGD）的BE患者是否受益于EET。LGD的诊断远 比HGD更常见，并且与EAC的风险较低相关，因此尚不清楚成本和 EET的并发症在这组患者中是合理的，或者他们是否应该简单地继续定期 监视内窥镜检查临床平衡的存在和这个问题的重要性表明， 在这一患者人群中进行内镜监测与EET的试验是我们目前研究中一个紧迫的、未满足的缺口。 关于治疗这种常见疾病的知识。我们在解决这一问题方面处于独特的地位 知识上的巨大差距，因为我们已经组建了一个多学科团队， 开展临床试验和生物标志物研究，以确保成功设计和高质量执行 SURVENT试验（监测与内镜治疗BE伴LGD）。本多中心随机 一项对照试验（n=530）将比较内镜监测和EET治疗LGD的效果， 统一的入选标准、设计和终点。本试验还将包括一个观察性队列组， 拒绝随机化但其他方面合格的受试者（最多150例受试者）。在我们的成就之后 在U34项目的资助期内，我们为U 01项目提出了以下目标：具体目标1将比较这两个目标 使用肿瘤进展率（进展为HGD或粘膜或粘膜）作为主要终点的方法 侵入性EAC）。具体目标#2将比较以患者为中心的结局，如健康相关生活质量 两个治疗组之间。具体目标#3将确定分子的效用（TissueCypher和 p53免疫组织化学）和成像（广域经上皮取样- WATS）生物标志物，以改善 接受监测和EET的BE伴LGD患者的风险分层。生物样本也将 在预先指定的时间点获得，以建立未来转化研究计划的生物储存库。的 这项工作与公共卫生的相关性很高。BE是一种常见疾病，影响2-3%的美国成年人 在人群中，LGD见于高达40%的BE患者。这是EAC的前身，数百万美元是 每年花费在BE和EAC患者的管理上。我们创新研究的影响将包括 为患有LGD的BE患者确定最佳的以患者为中心的治疗方法，这将告知护理 每年有数千名患者。

Project Summary/Abstract 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 or whether they should simply continue with periodic surveillance endoscopy. 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 are uniquely positioned to address this significant gap in knowledge as we have assembled a multidisciplinary team with the requisite expertise in the conduct of clinical trials and biomarker research to ensure successful design and high-quality execution of the SURVENT trial (Surveillance versus Endoscopic Therapy for BE with LGD). This multicenter randomized controlled trial (n=530) will compare endoscopic surveillance and EET for the management of LGD using uniform inclusion criteria, design and endpoints. This trial will also include an observational cohort arm for those who decline randomization but are otherwise eligible (up to 150 subjects). Following our achievements during the U34 grant period, we propose the following aims for the U01: 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 patient-centered outcomes such as health-related quality of life between the two treatment groups. Specific Aim #3 will determine the utility of molecular (TissueCypher and p53 immunohistochemistry) and imaging (wide-area transepithelial sampling – WATS) biomarkers to improve risk-stratification in BE with LGD patients undergoing surveillance and EET. Biological samples will also be obtained at pre-specified time points 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 and millions of dollars are spent yearly on the management of BE and EAC patients. 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.