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

通过风险分层社区参与计划验证用于早期检测胰腺癌的新型成像和分子测试

• 批准号: 10640704
• 负责人: Gregory A Cote
• 金额: $ 76.69万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640704
• 关键词: Address; Atrophic; Awareness; Biological Assay; Biological Markers; Biopsy; Blood; Blood Volume; Body Fluids; Cancer Biology; Case/Control Studies; Circulation; Clinic; Clinical; Clinical Trials; Collaborations; Community Outreach; Complex; Consumption; Contrast Media; Cyst; Data; Detection; Diagnosis; Diagnostic; Duct (organ) structure; Early Diagnosis; Eligibility Determination; Enrollment; Ensure; Excision; FDA approved; Fibrosis; Fingerprint; Focus Groups; Gadolinium; Genetic; High grade dysplasia; Home; Hydrogels; Image; Imaging Techniques; Inflammation; Interobserver Variability; Interview; Lesion; Liquid substance; Longitudinal Studies; Machine Learning; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Maps; Measures; Methods; Microelectrodes; Microfluidic Microchips; Mission; Modeling; Molecular; Morphology; Mucinous Neoplasm; Oregon; Pancreas; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia; Papillary; Patient Participation; Patients; Pattern; Phase; Plasma; Population; Protocols documentation; Reproducibility; Research; Resources; Rural Minority; Sampling; Science; Screening for cancer; Screening procedure; Source; Techniques; Testing; Time; Tissue Sample; Underrepresented Minority; Underrepresented Populations; Validation; Work; biomarker validation; biomedical referral center; chronic pancreatitis; cohort; community engagement; design; dielectric property; early screening; extracellular vesicles; high risk; high risk population; imaging biomarker; imaging modality; imaging science; implementation science; innovation; member; minority communities; multidisciplinary; nanoparticle; novel; outreach; pancreas imaging; participant enrollment; patient engagement; phase 3 study; population based; programs; recruit; risk stratification; screening; tissue registry; tumor; volunteer

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.

项目概要/摘要 为了诊断胰腺导管腺癌 (PDAC) 的前兆或早期阶段，新型筛查工具 必须在高危人群中使用新颖的成像策略应用液体生物标记物进行定位。俄亥俄州立大学 PCCDC 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。拟议研究的总体主题侧重于敏感性、可行性、 以及患者的接受程度。我们敏感的基于血液的筛查测试可以用最少量的 血液，并且可以根据进一步的发现轻松修改。如果是肯定的，这将促使应用可行的、 非对比、稳健的磁共振成像 (MRI) 协议，可增强 MRI 和磁力 胰腺共振胰管成像 (MRCP)，具有定量严格的 MR 指纹图谱 （MRF）。 MRF 可以同时量化与纤维化和炎症相关的参数（T1、T2、 和T1p）。我们假设这些参数在高度不典型增生（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耗时且技术复杂的 MR 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，MRF 可能会 在筛查经常接受 MRI 的人群时无需使用钆造影剂 MRCP。最后，我们将通过以下方式增加高风险个人进入 PCCDC 签名队列的人数： 利用现有的大型全州范围健康俄勒冈项目。此外，我们将与 我们的社区外展、研究和参与团队了解并解决参与障碍 PDAC 对少数群体成员（尤其是那些遭受不成比例苦难的群体）进行监测 来自 PDAC。这些努力将确保代表人数不足、最不可能参与的人群的参与 参与癌症筛查，同时为扩大 PCCDC Signature 的联盟使命做出贡献 队列。 OHSU 研究单位准备通过共享信息与 PCCDC 联盟进行有意义的合作 俄勒冈州胰腺组织登记处的现有资源（登记了超过 3,700 名患者），OHSU PRECEDE 联盟受试者（迄今为止已招募超过 100 名高风险个体）并可能扩展到其他 PRECEDE 中心和 OHSU 高危胰腺癌筛查诊所（超过 750 名患有胰腺癌的独特患者） 完成至少一项筛选测试）。此外，我们的团队还包括实施科学方面的专家，他们 设计并启动了健康俄勒冈项目，这是一个基于应用程序的平台，允许在家购买 通过邮寄工具包和基于人群的互动收集遗传数据，以发现高风险个体并与之互动。