Precision Management of Cystic Precursors to Pancreatic Cancer

胰腺癌囊性前体的精准治疗

• 批准号: 10203880
• 负责人: Pari Vijay Pandharipande
• 金额: $ 31.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 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 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203880
• 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.

项目概要/摘要 我们的目标是找到预防胰腺囊肿患者因胰腺癌死亡的最佳方法。 成像技术的进步使得无数以前看不见的胰腺囊肿被发现 以前，现在在 10% 以上的 MRI 患者和 >2% 的 CT 扫描不相关的患者中可见 当此类囊肿是意外且无症状时，它们被认为是“偶然的”。 导管内乳头状粘液性肿瘤 (IPMN)，是胰腺的惰性前体 导管腺癌（PDAC）是最常见的胰腺癌类型，预后较差。 随着PDAC患者的生存，胰腺囊肿已成为早期PDAC检测的首要目标。 建议大多数被诊断患有偶发性胰腺囊肿的患者进行影像学监测，但关键 定义监视的因素——例如成像的频率、方式和持续时间，以及何时进行监视 活检或手术——密切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此类囊肿的患者年龄较大且患有合并症。 倡导者强调，密切监测是早期 PDAC 检测的独特机会。 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，复制自然历史 偶然的胰腺囊肿，并用它来制定精确的管理方法。 借鉴我们团队现有的 PDAC 模拟模型，该模型已根据国家癌症中心的数据进行校准 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。 扩展该模型以复制偶然检测到的胰腺囊肿的自然史（目标 1）。 使用该模型来确定有效（目标 2）和具有成本效益（目标 3）的管理策略，这些策略适合 囊肿特征（大小、复杂性）和患者特征（年龄、合并症状况）最后，我们将。 评估新出现的血液和囊肿液生物标志物进一步改善管理的潜力（目标 4）。 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问题 研究团队正在解决仅靠观察研究或临床试验难以解决的问题。 非常适合，在胰腺癌护理和偶发性胰腺囊肿方面拥有良好的记录，并且 在开发数学模型方面拥有丰富的经验，这些模型已用于为卫生政策提供信息 国家层面的结果将有三个方面：1）偶发性胰腺囊肿的详细自然史模型； 2) 根据囊肿特征和患者特征定制治疗方法；3) a 未来几年推进胰腺癌囊性前体研究的路线图。