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

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.