Precision Management of Cystic Precursors to Pancreatic Cancer

胰腺癌囊性前体的精准治疗

• 批准号: 10442748
• 负责人: Pari Vijay Pandharipande
• 金额: $ 43.65万
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442748
• 关键词: Address; Advocate; Affect; Age; Biological Markers; Biopsy; Blood; Cancer Control; Cancer Etiology; Cessation of life; Characteristics; Clinical; Clinical Trials; Clinical Trials Design; Complement; Computer Simulation; Cost Effectiveness Analysis; Cyst; Cyst Fluid; Data; Data Sources; Detection; Diagnosis; Endoscopic Ultrasonography; Equilibrium; Frequencies; Future; General Hospitals; Goals; Guidelines; Harm Reduction; Health; Health Policy; Image; Indolent; Intervention; Life Expectancy; Link; Literature; Magnetic Resonance Imaging; Malignant neoplasm of pancreas; Massachusetts; Medical Societies; Medicare; Methods; Modality; Modeling; Monitor; Mucinous Neoplasm; National Cancer Institute; Natural History; Observational Study; Operative Surgical Procedures; Outcomes Research; Pancreatectomy; Pancreatic Cyst; Pancreatic Ductal Adenocarcinoma; Papillary; Pathway interactions; Patient Care; Patients; Prognosis; Publishing; Recommendation; Reporting; Research; Risk; SEER Program; Serous Cystadenoma; X-Ray Computed Tomography; base; cancer care; cancer invasiveness; comorbidity; cost; cost effective; cost estimate; experience; improved; innovation; mathematical model; models and simulation; mortality risk; older patient; overtreatment; pancreatic ductal adenocarcinoma model; patient population; personalized approach; personalized management; prevent; surveillance imaging

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 我们的目标是找到最好的方法来防止胰腺囊肿患者死于胰腺癌。近期 随着成像技术的进步，人们发现了无数从未见过的胰腺囊肿。 以前，现在有10%的接受核磁共振检查的患者和2%的接受CT扫描的患者有无关的 原因嘛。当这样的囊肿是意想不到的并且没有症状时，它们被认为是“偶然的”。大多数人 代表导管内乳头状粘液性肿瘤(IPMN)，它是胰腺的惰性前驱疾病 导管腺癌(PDAC)，最常见的胰腺癌类型。考虑到预后不佳和 对于PDAC患者的生存，胰腺囊肿已成为PDAC早期检测的首要目标。 对于大多数被诊断为偶发性胰腺囊肿的患者，建议进行影像监测，但关键是 定义监测的因素--例如，成像的频率、方式和持续时间，以及何时进行 活组织检查或手术-都是极具争议性的。密集监控的批评者对过度检测表示担忧 以及过度治疗，特别是考虑到许多患有此类囊肿的患者年龄较大，并伴有并发症。 倡导者强调，密切监测带来了及早发现PDAC的独特机会。 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 偶发胰腺囊性病变，并据此制定精准处理方法。我们的研究计划将 来自我们团队现有的PDAC仿真模型，该模型已根据国家癌症研究所的数据进行了校准 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。首先，我们将 扩展这一模型以复制偶然发现的胰腺囊肿的自然病史(目标1)。到时候我们会的 使用该模型确定有效(目标2)和成本效益(目标3)的管理战略，这些战略是为 囊性特征(大小、复杂性)和患者特征(年龄、合并症状态)。最后，我们会 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)。 这项拟议的研究具有创新性，因为它将先进的建模方法应用于有争议的 仅靠观察性研究或临床试验很难解决的问题。研究小组是 非常适合，在胰腺癌护理和偶发胰腺囊肿方面有良好的记录，并 在开发数学模型方面具有丰富的经验，这些模型已用于为卫生政策提供信息 国家层面。结果将有三个方面：1)偶发胰腺囊肿的详细自然病史模型； 2)根据囊性病变特征和患者特征，采取量身定制的处理方法；以及3)a) 未来几年推进胰腺癌囊性先兆研究的路线图。