Hereditary Pancreatic Cancer

Germline testing for hereditary cancer syndromes is underutilized across most health care settings. Using a learning health care approach, the Genomics-enabled Learning Health Systems (gLHS) network aims to evaluate the impact of a suite of implementation strategies to increase germline test ordering by oncology care teams (i.e., mainstreaming) for eligible patients with breast, pancreatic or colorectal cancer. Secondarily, the study will investigate completion of testing by eligible patients, as well as impact on overall rates of germline test ordering in patients with cancer. The network will bundle and deploy different implementation strategies across the clinical sites in three 6-month phases. A maintenance phase after the implementation periods will measure genetic testing rates without any additional implementation strategies to determine persistence of effects. The implementation strategies address clinician-level factors, and thus oncologists and their team members (e.g. advanced practice providers, nurse navigators, case managers) will be the focus of evaluating the impact of implementation strategies. Strategies that will be considered include provider education, audit and feedback reports, facilitation, peer support, and electronic health record (EHR) system optimization to support germline testing. Using the RE-AIM QuEST framework, outcomes will be assessed using mixed methods separately for each eligible cancer type. Data collection from the EHR, other relevant data sources, and qualitative provider feedback will be used to assess ordering and completion of tests and the effect of the implementation strategies on germline testing rates in oncology clinics.

Background: Pancreatic cancer (PC) is an aggressive cancer with only a 7% 5-year survival rate, primarily due to late-stage diagnosis. In Spain, its incidence is rising, and by 2030, it is expected to become the second leading cause of cancer-related death worldwide. Approximately 3% of PCs occur in the context of hereditary pancreatic cancer (HPC) predisposition syndromes. Studies have shown that up to 40% of genetic mutations associated with PC in individuals under 60 years old would not have been identified using traditional clinical criteria for genetic testing. Presymptomatic genetic testing is recommended for relatives of patients with hereditary syndromes to identify those at higher risk of PC and to include them in screening programs to alter the natural history of the disease. However, there is no robust evidence supporting the best tool for early diagnosis in at-risk individuals. Currently, screening relies on endoscopic ultrasound or magnetic resonance imaging, which yield suboptimal results. Aims: By studying the clinical, molecular, and genetic characteristics of PC patients and their families, this project aims to identify factors conferring higher PC risk and to adopt preventive measures while evaluating the efficacy of current screening strategies. Additionally, the project includes a traslational subproject to identify new hereditary genes associated with increased PC risk and novel molecules (biomarkers, specifically miRNAs) with diagnostic potential. These biomarkers could serve as non-invasive tools to identify individuals at increased risk of PC through blood tests, enabling preventive measures or early diagnosis. Given the low incidence of PC (albeit with high mortality), collaborative studies are essential to achieve meaningful results. The current project represents the first Spanish multicenter population-based registry for PC, integrating clinical data and biological sample collection alongside a control group. Its goal is to prevent PC and foster collaboration between basic research and clinical application in Spain within a proven collaborative framework. Establishing the best strategy to detect high-risk individuals for PC within the general population. Identifying new PC risk genes to expand the identification of at-risk individuals. Determining effective prevention strategies for high-risk individuals. Creating a national network, "PREVENPANC," for collaborative PC research, including the collection of biological samples (blood) from all enrolled patients.