Clinical Validation Center for Early Detection of Pancreatic Cancer

摘要 胰腺导管腺癌(PDAC)的早期发现是一个最优先考虑的领域，也是一个尚未得到满足的需求 以促进美国的公共卫生。某些患者亚群，例如那些有生殖系的患者 突变、粘液性胰腺囊肿和新发糖尿病(NOD)的风险高于PDAC的平均风险。 在前一个周期中，我们位于MD Anderson癌症中心的EDRN临床验证中心(CVC) (A)通过以下方式促进了首次、多机构、盲目的“生物标记物烘焙”活动 提供带注释的生物标记物，(B)在#年完成了EDRN定义的首批第三阶段生物标记物研究之一 使用诊断前样本的PDAC(Fahrmann等人，胃肠病学2021)，以及(C)充当 实施其他EDRN协作研究倡议，包括诊断前PDAC 成像联盟。我们的续签申请代表墨西哥湾沿岸-五大湖EDRN临床验证 胰腺癌中心(GCGLEC)由UTMDACC/Lyndon B Johnson医院(Harris Health， TX)、Henry Ford Health System(HFHS，Detroit，MI)和Ochsner Health System(OHS，新奥尔良，洛杉矶)以及 有三个主要目标：第一，实施多机构框架，收集最高质量 来自各种明确胰腺病理的患者的生物标本(包括早期PDAC， 胰腺囊性病变，以及其他良性胰腺疾病，如慢性胰腺炎、良性囊肿和 低恶性潜能的内分泌肿瘤)，以便进行生物标志物验证研究以早期发现 符合EDRN定义的第二阶段和第三阶段研究设计的PDAC。PDAC生物标志物研究现状 通常来自种族和少数族裔的代表很少，因此是 GCGLEC将通过从以下来源获得生物样品来解决生物标记物研究中的“差距差距” 代表不足的少数族裔。第二，GCGLEC将在我们已发表的第三阶段研究的基础上，利用 CA19-9、LRG1和TIMP-1的“锚板”，通过进行另外四项符合探头的研究 结合自身抗体，代谢物和额外的蛋白质生物标志物，以提高敏感性 在不影响99%或更高的特异性阈值的情况下诊断无症状的PDAC。这些EDRN- 已确定的第三阶段研究将在诊断前病例和从现有队列获得的对照中进行， 包括PLCO、WHI和所谓的“哈佛队列”(NHS、PHS、WHS和HPFS)以及正在进行的 发生应计的前瞻性队列，如NCI资助的新发高血糖和糖尿病(NOD) 以及PDAC的早期检测启动(EDI)，这是PANCAN和NCI之间的合作。第三, GCGLEC将作为EDRN内外合作活动的“枢纽”，包括 与由胰腺癌检测联盟(PCDC)资助的调查人员合作，并为 为PDAC早期进行EDRN批准的多机构“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.