Clinical Validation Center for Early Detection of Pancreatic Cancer

摘要 胰腺导管腺癌（PDAC）的早期检测是一个最优先的领域，也是一个未满足的需求 来促进美国的公共健康某些亚组的患者，如生殖细胞 突变、粘液性胰腺囊肿和新发糖尿病（NOD）的PDAC风险高于平均水平。 在前一个周期，我们位于MD安德森癌症中心的EDRN临床验证中心（CVC） （MDACC）：（a）通过以下方式促进在PDAC中进行首次多机构盲态“生物标志物烘烤”： 提供注释的生物标本，（B）完成了EDRN定义的首批III期生物标志物研究之一， 使用诊断前样本的PDAC（Fahrmann et al，Gastroenterology 2021），以及（c）用作 实施额外的EDRN合作研究计划，包括诊断前PDAC 成像联盟。我们的更新申请代表了海湾地区-大湖地区EDRN临床验证 胰腺癌中心（GCGLEC）由UTMDACC/林登B约翰逊医院（哈里斯健康， 德克萨斯州）、亨利福特卫生系统（HFHS，底特律，密歇根州）和奥克斯纳卫生系统（OHS，新奥尔良，洛杉矶）以及 有三个主要目标：第一，实施一个多机构框架，收集最高质量的 来自具有多种明确的胰腺病理（包括早期PDAC， 胰腺囊性病变和其他良性胰腺疾病，如慢性胰腺炎，良性囊肿， 低恶性潜力的内分泌肿瘤），以便进行生物标志物验证研究，用于早期检测 符合EDRN定义的II期和III期研究设计的PDAC。当前PDAC生物标志物研究 通常有少数种族和少数民族的代表，因此是一个主要的推动力， GCGLEC将通过从生物样本中获取生物样本来解决生物标志物研究中的“差距差距”。 代表性不足的少数民族。其次，GCGLEC将在我们已发表的3期研究的基础上， CA 19 -9、LRG 1和TIMP-1的“锚板”，通过进行四项额外的符合PRoBE的研究， 掺入自身抗体、代谢物和另外的蛋白质生物标志物，用于提高 诊断无症状PDAC而不损害99%或更高的特异性阈值。这些EDRN- 将在从现有队列中获得的诊断前病例和对照中进行定义的III期研究， 包括PLCO、WHI和所谓的“哈佛队列”（NHS、PHS、WHS和HPFS），以及正在进行的 正在进行招募的前瞻性队列，如NCI资助的新发高血糖症和糖尿病（NOD） 队列，以及PDAC中的早期检测启动（EDI），PanCAN和NCI之间的合作。第三、 全球地球信息环境控制中心将作为欧洲地面数据网络（EDRN）内外合作活动的“枢纽”，包括 与胰腺癌检测联盟（PCDC）资助的研究人员合作， 开展EDRN批准的PDAC早期多机构“临床效用”（4期研究）的基础 在CAP/CLIA环境中进行检测。

Abstract Early detection of pancreatic ductal adenocarcinoma (PDAC) is an area of highest priority and an unmet need for advancing public health in the United States. Certain sub-groups of patients, such as those with germline mutations, mucinous pancreatic cysts and new-onset diabetes (NOD) are at higher than average risk for PDAC. In the immediate prior cycle, our EDRN Clinical Validation Center (CVC) at MD Anderson Cancer Center (MDACC): (a) facilitated the conduct of the first ever, multi-institutional, blinded “biomarker bakeoff” in PDAC by providing annotated biospecimens, (b) completed one of the first EDRN-defined Phase 3 biomarker studies in PDAC using pre-diagnostic samples (Fahrmann et al, Gastroenterology 2021), and (c) served as a conduit for the implementation of additional EDRN collaborative research initiatives, including a pre-diagnostic PDAC imaging consortium. Our renewal application represents a Gulf Coast-Great Lakes EDRN Clinical Validation Center (GCGLEC) in Pancreatic Cancer is comprised of UTMDACC/Lyndon B Johnson Hospital (Harris Health, TX), Henry Ford Health System (HFHS, Detroit, MI) and Ochsner Health System (OHS, New Orleans, LA) and has three major objectives: First, to implement a multi-institutional framework for collecting the highest quality biospecimens from patients with a variety of well-defined pancreatic pathologies (including early stage PDAC, pancreatic cystic lesions, and other benign pancreatic diseases, such as chronic pancreatitis, benign cysts, and endocrine tumors of low malignant potential), in order to conduct biomarker validation studies for early detection of PDAC that conform to EDRN-defined Phase 2 and Phase 3 study design. Current PDAC biomarker studies typically have sparse representation from racial and ethnic minorities, and therefore a major impetus of the GCGLEC will be to address the “disparity gap” in biomarker research by obtaining biospecimens from underrepresented minorities. Second, the GCGLEC will build upon our published Phase 3 study utilizing the “anchor panel” of CA19-9, LRG1 and TIMP-1, by conducting four additional PRoBE-compliant studies that incorporate autoantibodies, metabolites and additional protein biomarkers for improving the sensitivity of diagnosing asymptomatic PDAC without compromising the 99% or greater specificity threshold. These EDRN- defined Phase 3 studies will be conducted in pre-diagnostic cases and controls obtained from existing cohorts, including the PLCO, WHI, and the so-called “Harvard cohorts” (NHS, PHS, WHS and HPFS), as well as ongoing prospective cohorts undergoing accrual, such as the NCI-funded New Onset Hyperglcyemia and Diabetes (NOD) cohort, and the Early detection Initiation (EDI) in PDAC, a collaboration between PanCAN and the NCI. Third, the GCGLEC will serve as a “hub” for collaborative activities within and outside the EDRN, including collaborations with investigators funded by the Pancreatic Cancer Detection Consortium (PCDC), and laying the foundations for conducting an EDRN-approved multi-institutional “clinical utility” (Phase 4 study) for PDAC early detection, within a CAP/CLIA environment.