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

项目摘要/摘要 Barrett‘s食道(BE)，一种与慢性食管炎相关的食管壁的化生改变 胃食道反流病是唯一已知的食管腺癌(EAC)的先兆。EAC是 美国增长最快的癌症之一，通常出现在晚期 并与令人沮丧的5年存活率有关。内窥镜根除治疗(EET)是 BE和高度不典型增生(HGD)或粘膜EAC患者的护理。然而，一个中央悬而未决的问题 问题是患有低度异型增生(LGD)的BE患者是否从EET中受益。LGD的诊断还很遥远 比HGD更常见，并与EAC的风险较低有关，因此尚不清楚这种成本和 EET的并发症在这组患者中是合理的，还是应该继续进行周期性的 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， 在这一患者群体中进行内窥镜监测与EET的试验是我们当前一个紧迫的、尚未填补的空白 关于这种常见疾病的治疗知识。我们在解决这一问题上处于独特的地位 知识差距很大，因为我们组建了一个拥有必要专业知识的多学科团队 进行临床试验和生物标志物研究，以确保成功的设计和高质量的执行 SURVENT试验(监测与内窥镜治疗合并LGD的BE)。这个多中心随机化 对照试验(n=530)将比较内窥镜监测和EET在管理LGD方面的应用 统一的纳入标准、设计和终点。这项试验还将包括一项观察性队列试验， 那些拒绝随机化但符合其他条件的人(最多150名受试者)。追随我们的成就 在U34授权期内，我们为U01提出了以下目标：具体目标#1将比较两者 使用肿瘤进展率的主要终点(进展到HGD或粘膜或 侵袭性EAC)。具体目标2将比较以患者为中心的结果，如与健康相关的生活质量 两个治疗组之间的差异。具体目标#3将确定分子(组织环磷脂和 P53免疫组织化学)和成像(广域跨皮细胞采样-WATS)生物标记物的改进 接受监测和EET的LGD患者BE的风险分层。生物样本也将被 在预先指定的时间点获得，以建立一个生物库，供未来的翻译研究倡议使用。这个 这项工作与公共卫生的相关性很高。BE是一种常见的疾病，影响美国2%-3%的成年人 人群和LGD在高达40%的BE患者中可见。这是EAC的前兆，数百万美元是 每年用于BE和EAC患者的管理。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，这将为 每年数以千计的病人。

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.