Precision Management of Cystic Precursors to Pancreatic Cancer

胰腺癌囊性前体的精准治疗

• 批准号: 10600582
• 负责人: Pari Vijay Pandharipande
• 金额: $ 12.92万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600582
• 关键词: Precision; Management; Cystic; Precursors; Pancreatic; Precision; Management; Cystic; Precursors; Pancreatic

PROJECT SUMMARY/ABSTRACT Our goal is to find the best ways to prevent pancreatic cancer deaths in patients with pancreatic cysts. Recent advances in imaging have led to the detection of innumerable pancreatic cysts that could never be seen before, now visible in >10% of patients who have an MRI and in >2% who have a CT scan for an unrelated reason. When such cysts are unexpected and asymptomatic, they are considered “incidental.” The majority represent intraductal papillary mucinous neoplasms (IPMNs), which are indolent precursors to Pancreatic Ductal AdenoCarcinoma (PDAC), the most common type of pancreatic cancer. Given the poor prognosis and survival of patients with PDAC, pancreatic cysts have become a primary target of early PDAC detection. Imaging surveillance is advised for most patients who are diagnosed with an incidental pancreatic cyst, but key factors that define surveillance – e.g., the frequency, modality, and duration of imaging, and when to pursue biopsy or surgery – are highly controversial. Critics of intensive surveillance raise concerns about overtesting and overtreatment, particularly given that many patients with such cysts are older and have comorbidities. Advocates emphasize the singular opportunity for early PDAC detection that arises from close monitoring. To address this problem, we will build a computer-based simulation model that replicates the natural history of incidental pancreatic cysts, and use it to formulate a precision management approach. Our research plan will draw from our team’s existing simulation model of PDAC, which is calibrated to data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program and published studies. First, we will extend this model to replicate the natural history of incidentally detected pancreatic cysts (Aim 1). We will then use the model to identify effective (Aim 2) and cost-effective (Aim 3) management strategies that are tailored to both cyst features (size, complexity) and patient characteristics (age, comorbidity status). Finally, we will evaluate the potential for emerging blood and cyst-fluid biomarkers to further improve management (Aim 4). The proposed research is innovative because it applies an advanced modeling approach to a controversial problem that will be difficult to solve with observational studies or clinical trials alone. The research team is well-suited, with an established track record in pancreatic cancer care and incidental pancreatic cysts, and with substantial experience in developing mathematical models that have been used to inform health policy at national levels. The results will be threefold: 1) a detailed natural history model of incidental pancreatic cysts; 2) a tailored approach to their management, based on cyst features and patient characteristics; and 3) a roadmap for advancing future research in cystic precursors to pancreatic cancer in the coming years.

项目摘要/摘要 我们的目标是找到预防胰腺囊肿患者胰腺癌死亡的最佳方法。最近的 成像的进步导致发现了几乎无法看到的无数胰腺囊肿 以前，现在在> 10％的患有MRI的患者和> 2％的CT扫描的患者中可见 原因。当这种囊肿是出乎意料的且无症状的时，它们被认为是“偶然的”。多数 代表导管内乳头膜肿瘤（IPMN），它们是胰腺的不稳定前体 导管腺癌（PDAC）是最常见的胰腺癌类型。鉴于预后不良和 PDAC患者的存活率，胰腺囊肿已成为早期PDAC检测的主要目标。 建议大多数被诊断出患有偶然胰腺囊肿但关键的患者进行成像监视 定义监视的因素 - 例如，成像的频率，方式和持续时间以及何时购买 活检或手术 - 高度争议。密集监视的批评者引起了人们对超越的担忧 并且过度治疗，特别是考虑到许多此类囊肿的患者年龄较大并且有合并症。 倡导者强调了由密切监测引起的早期PDAC检测的单一机会。 为了解决这个问题，我们将建立一个基于计算机的仿真模型，以复制 偶然的胰腺囊肿，并使用它来制定精确管理方法。我们的研究计划将 从我们团队现有的PDAC模拟模型中获取，该模型已校准为国家癌症的数据 研究所的监视，流行病学和最终结果（SEER）计划和已发表的研究。首先，我们会的 扩展该模型以复制偶然检测到的胰腺囊肿的自然历史（AIM 1）。然后我们会 使用该模型来识别有效的（AIM 2）和具有成本效益的管理策略，该策略量身定制 囊肿特征（大小，复杂性）和患者特征（年龄，合并症状态）。最后，我们会的 评估出现的血液和囊肿流体生物标志物进一步改善管理的潜力（AIM 4）。 拟议的研究具有创新性，因为它将高级建模方法应用于有争议的 仅通过观察性研究或临床试验而难以解决的问题。研究小组是 非常适合的，在胰腺癌护理和附带胰腺囊肿方面拥有既定记录 在开发用于为健康政策提供信息的数学模型方面的丰富经验 国家一级。结果将为三重：1）偶然胰腺囊肿的详细自然历史模型； 2）基于囊肿特征和患者特征的量身定制的管理方法； 3）a 在未来几年中，用于促进胰腺癌的囊性前体研究的路线图。