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，以识别出上皮卵巢癌风险高或升高的绝经后妇女（EOC）。我们将使用分式样本设计和妇女健康计划（WHI）观察性研究（OS），WHI临床临床试验（CT）和前列腺，肺，Colon和Ovary（PLCO）试验的分类样本设计（WHI）研究（WHI）观察性研究（OS），使用分类样本设计和数据制定并验证风险评估决策规则以及流行病学风险因素。作为初步工作的决策规则确定了所有绝经后妇女的10％ - 13％的风险升高，并预测了26％-58％的病例。预防外科预防，包括对输卵管（FTS）和卵巢的预防去除，被认为是预防高危女性中上皮卵巢癌（EOC），尤其是高级浆液性癌症（HGSC）的最佳方法。我们将开发一种工具，将女性分类为具有明显临床意义的风险分类，包括有关手术预防，成像，监视和常规护理的建议。在前两个目标中，我们将重点关注模型流行病学部分的开发，因为决策规则的血清标记部分已经基于广泛的发表工作而开发。在AIM 3中，我们将验证将流行病学风险因素与血清标记相结合的最终决策规则。我们在操作上将高风险定义为至少6个相对风险（RR），而风险的升高为RR至少为2。目标1：使用参与WHI OS，WHI CT和PLCO试验的随机选择的妇女，制定决定规则，可以单独使用流行病学变量识别EOC和HGSC的较高风险。使用每项研究中的其余妇女，验证每个人群中的每个决策规则。此目标中制定的决策规则将针对每个研究人群，以利用每个研究收集的所有流行病学数据。目标2：跨估算目标1中制定的决策规则，以确定最能确定在3个不同人群中EOC和HGSC风险较高的妇女的规则。这将需要对决策规则进行改进，以适应整个队列中数据收集的差异。用于开发的研究部分将用于确定最佳的共同规则，交叉验证将采用参加WHI OS，WHI CT和PLCO试验的妇女的剩余验证部分。该目标将确定最佳的流行病学决策规则，用于整体决策规则 在AIM 3中进行验证。AIM3：使用嵌套的病例对照研究血清标记数据以及每项研究的流行病学数据，验证AIM 2的最佳决策规则与规则的血清标记组成部分相结合，以识别这些人群中EOC和HGSC高高风险的女性。在此目标中，我们将验证最终的决策规则，该规则同时纳入了流行病学风险因素和血清标记。