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.

项目摘要 巴雷特食管（BE），一种异常柱状粘膜替代食管上皮的疾病。 胃食管反流病（GERD）引起的鳞状粘膜损伤，是唯一已知的 食管腺癌（EAC），一种致命的癌症，其发病率增加了8倍以上， 过去的50年在此期间，我们预防EAC死亡的主要策略基本上仍然是 不变-使用内窥镜检查筛查GERD患者的BE，并将BE患者纳入一项 内窥镜监视。这种停滞不前的战略未能阻止EAC的频率上升，因为目前 筛查实践是不够的，因为监测依赖于发现异型增生，异型增生是一种生物标志物， 相当大的缺点，引发癌症预防干预。新的筛选测试可用于 可以大大提高BE患者的识别率，但扩大筛查工作几乎没有意义。 仅仅是为了让更多的病人进入昂贵而无效的监测项目。TissueCypher BE检测， 其可以检测无异型增生的BE活检中的癌前分子和细胞变化， 有可能成为一种精确的风险分层测试，可以改变BE患者的实践模式。 回顾性病例对照研究，大量富集了发育不良和EAC的患者， 显示TissueCypher可以识别肿瘤进展高风险和低风险的BE患者。但如果 TissueCypher将在临床上用于风险分层，那么这些研究在一个 BE患者的“精选”人群将需要在非- 发育不良BE（NDBE）。理想情况下，验证将以随机对照试验（RCT）的形式进行，但 据认为，这种关于NDBE的研究需要大样本量和长时间的随访 站不住脚我们提出的研究利用了一种替代的创新设计来评估TissueCypher的预测性 没有RCT的站不住脚的要求。我们将使用活检标本 在大型社区GI实践中可用，以建立2，000名连续患者的无偏倚研究队列 在2008-2011年进行了基线内镜检查和活检显示NDBE，并且进行了≥1次随访 内窥镜检查进行至2021年12月。TissueCypher将在基线活检标本上运行， 我们将评估其在预测肿瘤进展方面的性能， 活组织检查我们还将确定TissueCypher的预测性能是否可以通过合并 临床变量和增强的图像分析功能。确认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和无效的内窥镜检查模式转变为 监测精准医学测试指导管理之一，并对高危患者进行早期干预 减少对低风险患者的监控。这将证明扩大BE筛查工作是合理的， 以具成本效益的方式遏止EAC的上升频率。