Validation of a risk assessment decision rule for epithelial ovarian cancer

上皮性卵巢癌风险评估决策规则的验证

• 批准号: 8735102
• 负责人: Nicole Denise Urban
• 金额: $ 18.57万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8735102
• 关键词: BRCA2 Mutation; Bilateral; CA-125 Antigen; Classification; Clinical; Clinical Trials; Colon; Data; Data Collection; Development; Disease; Early Intervention; Epidemiology; Epithelial ovarian cancer; Excision; Future; Goals; High Risk Woman; Image; Lesion; Lung; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Measurement; Modeling; Mutation; Nested Case-Control Study; Observational Study; Operative Surgical Procedures; Ovarian; Ovary; Performance; Population; Population Study; Postmenopause; Prevalence; Prevention; Prevention strategy; Process; Prospective Studies; Prostate; Publishing; Recommendation; Relative Risks; Research; Risk; Risk Assessment; Risk Factors; Risk Reduction; Salpingo-Oophorectomy; Sampling; Serous; Serum Markers; Study of serum; Time; Tubal Excisions; Validation; WFDC2 gene; Woman; Women' s Group; Women' s Health; Work; base; cohort; common rule; design; epidemiologic data; fimbria; high risk; improved; innovation; lifetime risk; mortality; mutation carrier; ovarian cancer prevention; prevent; prophylactic; prospective; public health relevance; routine care; screening; tool

DESCRIPTION (provided by applicant): Our goal is to develop a risk-classification tool to identify post-menopausal women who are at high or elevated risk for epithelial ovarian cancer (EOC). We will develop and validate a risk-assessment decision rule based on serum markers CA125 and HE4 as well as epidemiologic risk factors using a split-sample design and data from the Women's Health Initiative (WHI) Observational Study (OS), the WHI Clinical Trial (CT) and the Prostate, Lung, Colon and Ovary (PLCO) trial. A decision rule developed as preliminary work identified 10%- 13% of all post-menopausal women as elevated risk and predicted 26%-58% of cases. Surgical prevention consisting of prophylactic removal of fallopian tubes (FTs) and ovaries is recognized as the best approach to prevent epithelial ovarian cancer (EOC) and especially high grade serous cancer (HGSC) in high-risk women. We will develop a tool to categorize women into risk classifications that have clear clinical implications including recommendations for surgical prevention, imaging, surveillance and routine care. In the first 2 aims we will focus on development of the epidemiologic portion of the model because the serum marker portion of the decision rule has already been developed based on extensive published work. In Aim 3 we will validate the final decision rule that combines epidemiologic risk factors with serum markers. We operationally define high risk as relative risk (RR) of at least 6, and elevated risk as RR of at least 2. Aim 1: Using a randomly selected fraction of women participating in the WHI OS, WHI CT and the PLCO trial, develop decision rules to identify women at elevated risk for EOC and HGSC using epidemiologic variables alone. Using the remaining women from each study, validate each decision rule within each population. Decision rules developed in this aim will be specific to each study population in order to take advantage of all of the epidemiologic data collected by each study. Aim 2: Cross-validate the decision rules developed in Aim 1 to identify the rule that best identifies women at elevated risk for EOC and HGSC across the 3 different populations. This will require refinement of the decision rules to accommodate differences in data collection across the cohorts. The study fraction used for development will be used to identify the best common rule, and cross-validation will employ the remaining validation fraction of women participating in the WHI OS, WHI CT and the PLCO trial. This aim will identify the best epidemiologic decision rule for use in the overall decision rule to be validated in Aim 3. Aim 3: Using nested case-control study serum marker data as well as epidemiologic data from each study, validate the best decision rule from Aim 2 in combination with the serum marker component of the rule to identify women at elevated- and high-risk for EOC and HGSC in each of those populations. In this aim we will validate the final decision rule that incorporates both epidemiologic risk factors and serum markers.

描述（由申请人提供）：我们的目标是开发一种风险分类工具来识别患有上皮性卵巢癌（EOC）高风险或升高风险的绝经后女性。我们将使用分割样本设计和来自妇女健康倡议 (WHI) 观察性研究 (OS)、WHI 临床试验 (CT) 和前列腺、肺、结肠和卵巢 (PLCO) 试验的数据，根据血清标志物 CA125 和 HE4 以及流行病学危险因素制定和验证风险评估决策规则。作为初步工作制定的决策规则确定了所有绝经后妇女中 10%-13% 的风险较高，并预测了 26%-58% 的病例。包括预防性切除输卵管（FT）和卵巢在内的手术预防被认为是预防高危女性上皮性卵巢癌（EOC），尤其是高级别浆液性癌（HGSC）的最佳方法。我们将开发一种工具，将女性分为具有明确临床意义的风险分类，包括手术预防、影像学、监测和常规护理的建议。在前两个目标中，我们将重点关注模型的流行病学部分的开发，因为决策规则的血清标志物部分已经根据广泛发表的工作开发出来。在目标 3 中，我们将验证将流行病学危险因素与血清标志物相结合的最终决策规则。我们在操作上将高风险定义为相对风险 (RR) 至少为 6，将高风险定义为 RR 至少为 2。目标 1：使用随机选择的参与 WHI OS、WHI CT 和 PLCO 试验的女性比例，制定决策规则，仅使用流行病学变量来识别 EOC 和 HGSC 风险较高的女性。使用每项研究中剩余的女性，验证每个人群中的每条决策规则。为此目的制定的决策规则将针对每个研究人群，以便利用每个研究收集的所有流行病学数据。目标 2：交叉验证目标 1 中制定的决策规则，以确定最能识别 3 个不同人群中 EOC 和 HGSC 风险较高的女性的规则。这将需要完善决策规则，以适应不同群体之间数据收集的差异。用于开发的研究部分将用于确定最佳通用规则，交叉验证将采用参与 WHI OS、WHI CT 和 PLCO 试验的女性的剩余验证部分。该目标将确定在总体决策规则中使用的最佳流行病学决策规则，以 在目标 3 中得到验证。目标 3：使用巢式病例对照研究血清标志物数据以及每项研究的流行病学数据，结合规则的血清标志物部分验证目标 2 的最佳决策规则，以识别每个人群中 EOC 和 HGSC 高风险和高风险的女性。为此，我们将验证包含流行病学危险因素和血清标志物的最终决策规则。