Determining the clinical significance of intraluminal tumor cells in endometrial cancer

确定子宫内膜癌腔内肿瘤细胞的临床意义

• 批准号: 10005231
• 负责人: Ashley S. Felix
• 金额: $ 7.8万
• 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: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005231
• 关键词: Abdominal Cavity; Address; Affect; Calibration; Cancer Patient; Cancer Prognosis; Cell Survival; Cessation of life; Characteristics; Clinical; Clinical Data; Cytology; Data; Diagnosis; Diagnostic Neoplasm Staging; Discipline of obstetrics; Discrimination; Disease; Endometrial Carcinoma; Future; Goals; Guidelines; Gynecology; Hematoxylin and Eosin Staining Method; Histologic; Histology; Hospitals; Indolent; Institution; International; Investigation; Lead; Literature; Localized Disease; Malignant - descriptor; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Mammalian Oviducts; Measures; Metastatic Endometrial Carcinoma; Microscopic; Modeling; Ohio; Outcome; Pathogenesis; Pathologist; Pathology; Pattern; Performance; Postoperative Period; Primary Neoplasm; Prognostic Factor; Publishing; Recurrence; Resources; Risk stratification; Sampling; Selection for Treatments; Serous; Slide; Staging; Subgroup; Time; Transportation; United States; Universities; Update; Uterus; Woman; Work; base; cancer cell; cancer survival; clinically relevant; clinically significant; digital imaging; evidence base; image archival system; improved; individualized medicine; large datasets; mortality; neoplastic cell; outcome forecast; patient subsets; power analysis; predictive modeling; prognostic; prospective; statistics; survival outcome; survival prediction; tumor

PROJECT SUMMARY/ABSTRACT Mortality from endometrial cancer, the most common gynecologic malignancy in the United States, increased by 2% per year between 2010 and 2014, one of the few cancers to demonstrate rising mortality rates. The most powerful prognostic factor affecting endometrial cancer mortality is stage, which details the extent to which the primary tumor has spread beyond the uterus. Over time, staging criteria have evolved as new clinical data have emerged; however, one potentially important mode of spread not incorporated in endometrial cancer stage criteria is transtubal spread, which occurs when endometrial cancer cells are exfoliated through the fallopian tubes into the abdominal cavity. Despite the recognition that endometrial cancer cells have the capacity for cellular detachment and transtubal transportation, and that this mechanism co-occurs with other aggressive tumor characteristics, we lack empirical data on the prognostic impact of transtubal spread and whether this relationship is modified by other tumor characteristics. The overarching goals of the proposed study are to determine precise estimates of the relationship between intraluminal tumor cells (ILTCs) — an objective measure of transtubal spread — and clinical outcomes, and to assess whether incorporation of this tumor feature improves predictive accuracy. To achieve our goals, we will pool resources from five large academic hospitals. We will collect digital images of archived fallopian tube slides and conduct a pathology review to determine ILTC presence in 1,429 endometrial cancer patients. This information will be merged with existing clinical data to determine the relationship between ILTCs and survival outcomes according to histological subtype and stage (Aim 1). We will also examine whether the addition of ILTCs improves prognostic accuracy (Aim 2). Results from our published pilot data lead us to expect that ILTC presence will be associated with survival, particularly among women diagnosed with serous tumors or stage I tumors. Moreover, we expect to observe greater accuracy in prediction of survival outcomes once stage has been revised to incorporate ILTC status. This investigation will be the first well-powered analysis of the impact of transtubal spread on endometrial cancer prognosis. Our results have high translational potential for refining stage criteria and improving risk stratification, in order to better guide post-operative treatment decisions and reduce endometrial cancer mortality.

项目概要/摘要 子宫内膜癌是美国最常见的妇科恶性肿瘤，其死亡率有所增加 2010 年至 2014 年间每年增加 2%，是少数死亡率不断上升的癌症之一。 影响子宫内膜癌死亡率的最有力的预后因素是分期，它详细说明了子宫内膜癌死亡率的程度 随着时间的推移，原发肿瘤已扩散到子宫以外，分期标准已发展成为新的临床标准。 数据已经出现；然而，子宫内膜癌并未纳入一种潜在的重要传播模式。 分期标准是经输卵管扩散，当子宫内膜癌细胞通过输卵管脱落时就会发生这种情况。 尽管人们认识到子宫内膜癌细胞具有输卵管进入腹腔的能力。 细胞脱离和经输卵管运输的能力，并且这种机制与其他机制同时发生 由于侵袭性肿瘤特征，我们缺乏关于经输卵管播散的预后影响的经验数据和 这种关系是否会被其他肿瘤特征所改变。 研究的目的是确定腔内肿瘤细胞（ILTC）之间关系的精确估计—— 客观测量经输卵管扩散和临床结果，并评估是否将其纳入 为了实现我们的目标，我们将汇集五个大的资源。 我们将收集存档的输卵管切片的数字图像并进行病理学检查。 审查以确定 1,429 名子宫内膜癌患者中是否存在 ILTC。该信息将与该信息合并。 根据现有的临床数据确定 ILTC 与生存结果之间的关系 我们还将检查添加 ILTC 是否可以改善预后。 准确性（目标 2）。我们发布的试点数据的结果使我们预计 ILTC 的存在将与之相关。 生存率，特别是在诊断患有浆液性肿瘤或阶段性肿瘤的女性中，我们预计。 一旦阶段被修改以纳入，观察生存结果预测的更高准确性 ILTC 状态。这项调查将是首次对经输卵管传播的影响进行强有力的分析。 我们的结果对于完善分期标准和预测具有很高的转化潜力。 改善风险分层，以便更好地指导术后治疗决策并减少子宫内膜异位 癌症死亡率。