Validation of novel imaging and molecular tests for early detection of pancreatic cancer through risk-stratified community engagement programs

项目总结/摘要 为了诊断胰腺导管腺癌（PDAC）的前体或早期阶段， 必须在高危人群中使用新型成像策略应用液体生物标志物进行定位。关于OHSU PCDC研究单位提出了三个目标，突出其在癌症生物学，成像， 和实施科学。拟议研究的首要主题侧重于敏感性，可行性， 患者的可接受性。我们的灵敏的血液筛查测试可以应用于最少量的 血液，并很容易修改的基础上进一步的发现。如果是肯定的，这将促使适用一个可行的， 增强MRI和磁共振成像（MRI）的非造影剂和稳健的MRI方案 胰腺磁共振胰胆管成像（MRCP）与定量严格的MR指纹 （管理成果框架）。MRF可以同时量化与纤维化和炎症相关的参数（T1，T2， T1P）。我们假设这些参数在高度异型增生中上调（例如，高风险 导管内乳头状粘液性肿瘤（IPMN）和2-3级胰腺上皮内瘤变（PanIN）） 和早期胰腺导管腺癌（PDAC）。此外，定量MRI将降低高 MR解释的观察者间差异以及对耗时且技术复杂的MR的要求 在胰腺转诊中心之外实施可能具有挑战性的协议。如果成功，管理成果框架可 证实了在接受频繁MRI的筛查人群中对钆基造影剂的需求， MRCP。最后，我们将通过以下方式增加高风险个体入组PCDC签名队列， 利用现有的大型全州队列，健康俄勒冈州项目。此外，我们将与 我们的社区外展，研究和参与团队了解和解决参与的障碍， PDAC对少数族裔社区成员的监督，特别是那些遭受暴力侵害的人 PDAC的。这些努力将确保代表性不足的人口的参与，因为他们最不可能 参与癌症筛查，同时为扩大PCDC的联盟使命做出贡献 同伙 OHSU研究单位准备通过分享与PCDC联盟有意义的合作 来自俄勒冈州胰腺组织登记处的现有资源（入组> 3，700例患者），OHSU PRECEDE 联合体受试者（迄今为止招募的高风险个体> 100例），并可能扩展至其他PRECEDE 中心和OHSU高风险胰腺癌筛查诊所（> 750名患有 至少完成一次筛选测试）。此外，我们的团队还包括实施科学专家， 我已经设计并启动了健康俄勒冈州项目，这是一个基于应用程序的平台，允许在家里购买 通过邮寄工具包和基于人群的互动来发现高风险个体并与之互动，

PROJECT SUMMARY / ABSTRACT To diagnose pancreatic ductal adenocarcinoma (PDAC) in its precursor or early stages, novel screening tools must apply liquid biomarkers with localization using novel imaging strategies in high-risk populations. The OHSU PCDC Research Unit proposes three aims highlighting its multidisciplinary strengths in cancer biology, imaging, and implementation science. The overarching theme of the proposed research focuses on sensitivity, feasibility, and patient acceptability. Our sensitive blood-based screening test can be applied with minimal quantities of blood and is easily modifiable based on further discoveries. If positive, this would prompt application of a feasible, non-contrast, and robust magnetic resonance imaging (MRI) protocol that augments MRI and magnetic resonance chlangiopancreatography (MRCP) of the pancreas with quantitatively rigorous MR Fingerprinting (MRF). MRF can simultaneously quantify parameters that are associated with fibrosis and inflammation (T1, T2, and T1p). We hypothesize that these parameters are upregulated in high-grade dysplasia (e.g., high-risk intraductal papillary mucinous neoplasms (IPMNs) and grade 2-3 pancreatic intraepithelial neoplasia (PanIN)) and early-stage pancreatic ductal adenocarcinoma (PDAC). Further, quantitative MRI will reduce the high interobserver variability of MR interpretation and requirement for time consuming and technically complex MR protocols that can be challenging to implement outside of pancreas referral centers. If successful, MRF may obviate the need for Gadolinium based contrast agents in screening populations undergoing frequent MRI and MRCP. Finally, we will increase enrollment of high-risk individuals into PCDC Signature Cohorts, through leveraging an existing large, statewide cohort, Healthy Oregon Project. Further, we will work collaboratively with our Community Outreach, Research & Engagement team to understand and address barriers to engagement in PDAC surveillance among members of minoritized communities, particularly those who suffer disproportionally from PDAC. These efforts will ensure participation among underrepresented populations who are least likely to take part in cancer screening while contributing to the consortium mission of expanding PCDC Signature Cohorts. The OHSU Research Unit is prepared to meaningfully collaborate with the PCDC Consortium by sharing existing resources from the Oregon Pancreas Tissue Registry (> 3,700 patients enrolled), OHSU PRECEDE consortium subjects (> 100 high-risk individuals enrolled to date) and potential expansion to other PRECEDE centers, and the OHSU High Risk Pancreatic Cancer Screening clinic (> 750 unique patients who have completed at least one screening test). In addition, our team includes experts in implementation science who have designed and activated the Healthy Oregon Project, an app-based platform that allows at-home acquisition of genetic data through mail-in kits and population-based interaction to find and interact with high-risk individuals.