TissueCypher Testing for Risk Assessment in Barretts Esophagus

 描述(由申请人提供)：巴雷特食道是一种肿瘤前疾病，患者容易发展为食管腺癌(EAC)。在美国，大约有300万人患有巴雷特氏食道，他们经常通过内窥镜检查和食道活检的病理分析进行筛查。筛查的目标是及早发现癌前病变，以便能够采取干预措施预防EAC。然而，病理分析是主观的，容易发生变化，无法预测哪些患者会发展为EAC。对准确的预后测试的需求尚未得到满足，以识别需要治疗干预以预防EAC的高危患者，以及识别可能免除不必要的、昂贵的治疗和监测的低风险患者。这种检测是减少EAC发病率和提高这一疾病领域卫生保健支出效率的关键。拟议的第二阶段研究的主要目标是验证一种名为TisseCypher的预后测试，该测试预测Barrett‘s食道患者未来发展为高度不典型增生(HGD)和EAC的风险。这项拟议研究的技术创新是Cernostics的TIssueCypher技术，这是一种基于系统生物学的解剖病理学方法。该技术使用多路荧光标记关键组织系统生物标记物，包括组织标本中的恶性、免疫和间质过程，并使用全幻灯片荧光成像和图像分析来量化组织形态背景下的生物标记物。这与多变量分类器相结合，将生物标记物数据与临床变量相结合，以产生诊断、预后和预测分数。TIseCypher技术的技术和科学价值和可行性已通过其他资金来源在第一阶段类型的研究中得到证明。初步研究评估了巴雷特食道患者的多机构队列中的14个生物标志物和形态。选择了一套最佳的6个生物标记物、15个来自生物标记物和形态的图像分析测量结果以及一个多变量分类器，这构成了TIseCypher Barrett风险评估测试的基础，该测试将在第二阶段研究中得到验证。第二阶段研究的具体目标是开发TisseCypher测试的最终格式，并进行商业化所需的分析和临床性能研究。Cernostics、匹兹堡大学和克利夫兰诊所的研究人员联盟将重新配置测试格式，并对TisseCypher测试进行分析性和独立的临床验证研究，目标是通过CLIA认证的实验室提供该测试作为实验室开发的测试(LDT)。这项测试将作为一项服务提供给胃肠病专家和病理学家，使Barrett‘s患者能够准确、个性化地进行风险分层，以改进疾病管理并降低EAC的发生率。

 DESCRIPTION (provided by applicant): Barrett's esophagus is a pre-neoplastic disease that predisposes patients to development of esophageal adenocarcinoma (EAC). Approximately 3 million people in the US have Barrett's esophagus and they are frequently screened by endoscopy with pathological analyses of esophageal biopsies. The goal of the screening is to detect premalignant changes early to enable interventions to prevent EAC. However, the pathology analyses are subjective and prone to variation and cannot predict which patients will develop EAC. There is an unmet need for accurate prognostic tests to identify high risk patients who require therapeutic interventions to prevent EAC and to identify low risk patients who may be spared unnecessary, costly therapy and surveillance. Such tests are key to reducing EAC incidence and improving the efficiency of health care spending in this disease area. The broad objective of the proposed Phase II study is to validate a prognostic test, termed TissueCypher, which predicts future risk of developing high grade dysplasia (HGD) and EAC in patients with Barrett's esophagus. The technological innovation of the proposed study is Cernostics' TissueCypher technology, a systems biology-based approach to anatomic pathology. The technology employs multiplexed fluorescence labeling of key tissue system biomarkers, including malignant, immune and stromal processes in tissue specimens, with whole slide fluorescence imaging and image analysis to quantify biomarkers in the context of tissue morphology. This is coupled to multivariate classifiers to integrate biomarker data with clinical variables to produce diagnostic, prognostic and predictive scores. The technical and scientific merit and feasibility of the TissueCypher technology has been demonstrated in Phase I stage-type of research through other funding sources. Preliminary studies have evaluated 14 biomarkers and morphology in a multi- institution cohort of patients with Barrett's esophagus. An optimal set of 6 biomarkers, 15 image analysis measurements derived from the biomarkers and morphology and a multivariate classifier have been selected, which form the basis of the TissueCypher Barrett's risk assessment test that will be validated in the Phase II study. The specific aims of the Phase II study are to develop the final format of the TissueCypher test and perform the analytical and clinical performance studies that are required for commercialization. The consortium of investigators at Cernostics, University of Pittsburgh and Cleveland Clinic will reconfigure the test format and perform analytical and independent clinical validation studies on the TissueCypher test towards the goal of offering the test as a laboratory-developed test (LDT) via a CLIA-certified lab. The test will be offered as a service to gastroenterologists and pathologists to enable accurate, individualized risk stratification for Barrett's patients to improe disease management and reduce the incidence of EAC.