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

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.

项目总结/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 影像学的进步已经使我们发现了无数以前从未发现过的胰腺囊肿 以前，现在在>10%的接受MRI检查的患者中可见，在>2%的接受CT扫描的患者中可见。 原因的当这种囊肿是意外的和无症状的，他们被认为是“偶然的”。大多数 代表导管内乳头状粘液性肿瘤（IPMN），是胰腺癌的惰性前体， 胰腺癌是胰腺癌中最常见的一种。鉴于预后不佳， 胰腺囊肿已成为PDAC早期检测的主要目标。 对于大多数被诊断为偶发性胰腺囊肿的患者，建议进行影像学监测， 定义监视的因素-例如，成像的频率、模式和持续时间，以及何时进行 活组织检查还是手术都是有争议的。对强化监测的批评者提出了对过度检测的担忧 和过度治疗，特别是考虑到许多患有这种囊肿的患者年龄较大，并且患有合并症。 倡导者强调，早期PDAC检测的唯一机会来自密切监测。 为了解决这个问题，我们将建立一个基于计算机的模拟模型，复制自然历史， 偶发性胰腺囊肿，并使用它来制定精确的管理方法。我们的研究计划将 从我们团队现有的PDAC模拟模型中提取，该模型是根据国家癌症中心的数据校准的。 研究所的监测，流行病学和最终结果（SEER）计划和已发表的研究。一是 扩展该模型以复制偶然发现的胰腺囊肿的自然史（目标1）。然后我们将 使用该模型来确定有效的（目标2）和成本效益（目标3）的管理战略， 囊肿特征（大小、复杂性）和患者特征（年龄、合并症状态）。最后我们将 评估新出现的血液和囊液生物标志物的潜力，以进一步改善管理（目标4）。 拟议的研究是创新的，因为它应用了一种先进的建模方法来解决一个有争议的问题。 这个问题很难单独通过观察性研究或临床试验来解决。研究小组正在 非常适合，在胰腺癌护理和偶发胰腺囊肿方面有着既定的记录， 在开发用于为卫生政策提供信息的数学模型方面拥有丰富的经验， 国家一级。结果将是三方面的：1）一个详细的自然历史模型的偶然胰腺囊肿; 2)根据囊肿特征和患者特征，采用量身定制的方法进行管理;以及3） 在未来几年推进胰腺癌囊性前体研究的路线图。