Stratification of Cancer Risk in Patients with Non-Dysplastic Barrett's Esophagus using TissueCypher: The SCRiBE study

使用 TissueCypher 对非发育性巴雷特食管患者的癌症风险进行分层：SCRiBE 研究

• 批准号: 10561001
• 负责人: Rebecca Critchley-Thorne
• 金额: $ 59.27万
• 依托单位: BAYLOR RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10561001
• 关键词: Address; Barrett Esophagus; Biological Assay; Biological Markers; Biopsy; Biopsy Specimen; Case/Control Studies; Categories; Cessation of life; Clinical; Cohort Studies; Communities; Consumption; Data; Development; Dysplasia; Early Intervention; Endoscopic Biopsy; Endoscopy; Enrollment; Esophageal Adenocarcinoma; Esophagus; Frequencies; Gastroesophageal reflux disease; General Population; Health Care Costs; High grade dysplasia; High-Risk Cancer; Image Analysis; Image Enhancement; Incidence; Individual; Malignant - descriptor; Malignant Neoplasms; Managed Care; Molecular; Mucous Membrane; Pathology; Patients; Performance; Policies; Population; Prevention strategy; Protocols documentation; Public Health; Publishing; Randomized, Controlled Trials; Recommendation; Research; Research Design; Retrospective Studies; Risk; Risk Factors; Running; Sample Size; Specimen; Stratification; Surveillance Program; Symptoms; Testing; Time; Validation; cancer prevention; cancer risk; carcinogenicity; clinical practice; clinical risk; cohort; cost effective; design; follow-up; high risk; improved; individual patient; innovation; patient population; precision medicine; premalignant; prevent; preventive intervention; programs; progression risk; risk prediction; risk stratification; screening; standard of care; stem; technological innovation; tool; trial comparing; tumor; tumor progression

Project Summary Barrett’s esophagus (BE), the condition in which an abnormal columnar mucosa replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease (GERD), is the only known precursor of esophageal adenocarcinoma (EAC), a deadly cancer whose incidence has increased more than eight-fold over the past 50 years. During this time, our primary strategy for preventing EAC deaths has remained essentially unchanged - using endoscopy to screen GERD patients for BE, and enrolling BE patients in a program of endoscopic surveillance. This stagnant strategy has failed to stem the rising frequency of EAC because current screening practices are inadequate, and because surveillance relies on finding dysplasia, a biomarker with considerable shortcomings, to trigger a cancer-preventive intervention. New screening tests are available that could profoundly increase identification of BE patients, but it makes little sense to expand screening efforts merely to enter more patients into expensive, ineffective surveillance programs. The TissueCypher BE Assay, which can detect precancerous molecular and cellular changes in BE biopsies without dysplasia, has the potential to be a precision risk-stratification test that could change the practice paradigm for BE patients. Retrospective, case-control studies, heavily enriched with patients who developed dysplasia and EAC, have shown that TissueCypher can identify BE patients at high and low risk for neoplastic progression. However, if TissueCypher is to be used clinically for risk stratification, then the promising results of these studies in a “cherry-picked” population of BE patients will need validation in a general population of patients with non- dysplastic BE (NDBE). Ideally, validation would be in the form of a randomized, controlled trial (RCT), but the large sample size and lengthy follow-up durations required for such a study on NDBE have been deemed untenable. Our proposed study utilizes an alternative, innovative design to assess TissueCypher’s predictive performance accurately without the untenable requirements of an RCT. We will use biopsy specimens already available in a large community GI practice to establish an unbiased study cohort of 2,000 consecutive patients who had baseline endoscopies with biopsies showing NDBE in 2008-2011, and who had ≥1 follow-up endoscopies performed up to December 2021. TissueCypher will be run on baseline biopsy specimens, and we will assess its performance in predicting neoplastic progression as identified in subsequent endoscopic biopsies. We also will determine if TissueCypher’s predictive performance can be improved by incorporating clinical variables and enhanced image analysis features. Validation of TissueCypher’s ability to risk-stratify BE patients could shift the BE clinical practice paradigm from one of expensive and ineffective endoscopic surveillance to one of precision medicine test-guided management with early intervention for high-risk patients and reduced surveillance for low-risk patients. This would justify expanding BE screening efforts, and could stem the rising frequency of EAC in a cost-effective manner.

项目概要 巴雷特食管 (BE)，一种异常的柱状粘膜取代食管的病症 胃食管反流病 (GERD) 损害的鳞状粘膜是唯一已知的前兆 食管腺癌（EAC）是一种致命的癌症，其发病率比过去增加了八倍多 过去50年。在此期间，我们预防 EAC 死亡的主要策略本质上仍然是 不变 - 使用内窥镜检查 GERD 患者的 BE，并将 BE 患者纳入以下计划： 内窥镜监视。这种停滞不前的策略未能阻止 EAC 频率的上升，因为目前 筛查做法不充分，而且因为监测依赖于发现不典型增生，这是一种具有以下特征的生物标志物： 相当大的缺点，引发癌症预防干预措施。新的筛选测试可用 可以极大地提高 BE 患者的识别率，但扩大筛查工作意义不大 只是为了让更多的患者参与昂贵且无效的监测计划。 TissueCypher BE 检测， 它可以在BE活检中检测癌前分子和细胞变化，而没有不典型增生，具有 可能成为一种精确的风险分层测试，可以改变 BE 患者的实践范式。 回顾性病例对照研究，大量涉及发育不良和 EAC 的患者， 表明 TissueCypher 可以识别肿瘤进展高风险和低风险的 BE 患者。然而，如果 TissueCypher 将在临床上用于风险分层，然后这些研究的有希望的结果 “精挑细选”的 BE 患者群体需要在非患有普通疾病的患者群体中进行验证 发育不良BE (NDBE)。理想情况下，验证应采用随机对照试验 (RCT) 的形式，但 NDBE 的此类研究需要大样本量和漫长的随访时间 站不住脚的。我们提出的研究利用另一种创新设计来评估 TissueCypher 的预测能力 准确地表现，无需 RCT 的难以满足的要求。我们将已经使用活检标本 可在大型社区胃肠病实践中建立一个由 2,000 名连续患者组成的公正研究队列 2008-2011 年进行基线内窥镜检查并活检显示 NDBE 的人，以及进行≥1 次随访的人 截至 2021 年 12 月进行的内窥镜检查。TissueCypher 将在基线活检标本上运行，并且 我们将评估其在预测肿瘤进展方面的表现，如随后的内窥镜检查所确定的那样 活检。我们还将确定是否可以通过合并来提高 TissueCypher 的预测性能 临床变量和增强的图像分析功能。验证 TissueCypher 对 BE 进行风险分层的能力 患者可以将 BE 临床实践范式从昂贵且无效的内窥镜检查转变为一种 对高危患者进行早期干预的精准医学测试指导管理之一的监测 并减少对低风险患者的监测。这将证明扩大 BE 筛查工作是合理的，并且可以 以具有成本效益的方式阻止 EAC 频率的上升。