Comprehensive Systematic Evidence Review of the Clinical Utility of Polygenic Risk Scores for Hepatocellular Carcinoma and Pancreatic Cancer Risk Assessment

项目摘要 本申请是为了响应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 23-046.肝细胞癌（HCC）和胰腺癌是癌症相关死亡的主要原因 在美国，迫切需要有效的早期发现和预防策略，以改变患者的 结果。多基因风险评分（PRS）在遗传研究中的出现代表了一个突破性的进展。 有机会完善HCC和胰腺癌的风险评估和临床管理。该项目将 进行一项最新的科学系统性证据审查，以严格检查PRS对这些疾病的临床效用。 恶性肿瘤，为临床实践中的知情决策提供了坚实的基础。我们的多学科 团队，拥有广泛的专业知识，在系统评价和多样化的领域，生物医学信息学， 生物统计学，统计遗传学，癌症流行病学，临床试验设计，肿瘤学和癌症控制-将 严格应用既定的知识综合准则来执行拟议的补充。这 细致的方法将使我们能够识别准备进行临床试验的PRS模型，评估其局限性， 挑战，并确定其临床实用性。此外，我们还将评估 PRS在临床实践中的实施，探索创新策略，将PRS与非PRS模型相结合， 增强癌症风险预测，并提出评估PRS的最佳研究设计和方法 功效和有效性。我们进行这项全面系统性证据审查的强大框架 包括五个基本步骤：1）提出问题，2）确定相关工作，3）评估 研究，4）总结证据，5）解释发现。我们全面的搜索策略将 包括主要的生物医学和健康科学电子数据库、灰色文献和在线PRS 数据库，确保进行全面分析。使用预测模型偏差风险（ROB）评估工具 （PROBAST），我们将严格评估审查研究的质量和适用性。项目完成后， 将为实施PRS的潜在益处、危害和临床实用性提供不可或缺的证据 用于HCC和胰腺癌风险评估。我们的发现将为未来的研究提供建议 方向，并有助于制定以证据为基础的指南，用于癌症预防，早期 检测和管理，最终在个性化医疗的新时代改善患者的治疗效果。 癌症护理

Project Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 23-046. Hepatocellular carcinoma (HCC) and pancreatic cancer, as leading causes of cancer-related mortality in the United States, urgently necessitate effective early detection and prevention strategies to transform patient outcomes. The advent of polygenic risk scores (PRS) in genetic research represents a groundbreaking opportunity to refine risk assessment and clinical management for HCC and pancreatic cancer. This project will conduct a state-of-the-science systematic evidence review to critically examine the clinical utility of PRS for these malignancies, providing a solid foundation for informed decision-making in clinical practice. Our multidisciplinary team, boasting extensive expertise in systematic reviews and a diverse array of fields—biomedical informatics, biostatistics, statistical genetics, cancer epidemiology, clinical trials design, oncology, and cancer control—will rigorously apply established knowledge synthesis guidelines to execute the proposed supplement. This meticulous approach will enable us to identify PRS models poised for clinical trials, evaluate their limitations and challenges, and determine their clinical utility. Furthermore, we will assess the potential benefits and harms of PRS implementation in clinical practice, explore innovative strategies to integrate PRS with non-PRS models for enhanced cancer risk prediction and propose optimal study designs and methodologies for evaluating PRS efficacy and effectiveness. Our robust framework for conducting this comprehensive systematic evidence review comprises five essential steps: 1) framing the questions, 2) identifying relevant work, 3) assessing the quality of studies, 4) summarizing the evidence, and 5) interpreting the findings. Our comprehensive search strategy will encompass major biomedical and health sciences electronic databases, the grey literature, and online PRS repositories, ensuring a thorough analysis. Employing the Prediction Model Risk of Bias (ROB) Assessment Tool (PROBAST), we will rigorously assess reviewed studies’ qualities and applicability. Upon completion, this project will generate indispensable evidence on the potential benefits, harms, and clinical utility of PRS implementation for HCC and pancreatic cancer risk assessments. Our findings will inform recommendations for future research directions and contribute to developing evidence-based guidelines for PRS use in cancer prevention, early detection, and management, ultimately leading to improved patient outcomes in a new era of personalized cancer care.