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: 9808923
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9808923
• 关键词: Abdominal Cavity; Address; Affect; Calibration; Cancer Patient; Cancer Prognosis; Cell Survival; Cessation of life; Characteristics; Clinical; Clinical Data; Cytology; Data; Data Set; 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; 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.

项目摘要/摘要 子宫内膜癌的死亡率是美国最常见的妇科恶性肿瘤 在2010年至2014年期间，每年2％，这是少数显示死亡率上升的癌症之一。这 影响子宫内膜癌死亡率的最强大的预后因素是阶段，该阶段详细介绍了 原发性肿瘤已超出子宫。随着时间的流逝，分期标准随着新的临床发展而发展 数据出现了；但是，一种潜在的重要传播方式未纳入子宫内膜癌 阶段标准是跨史蒂比扩散，发生在子宫内膜癌细胞通过 输卵管进入腹腔。尽管认识到子宫内膜癌细胞具有 细胞脱离和transtubal运输的能力，该机制与其他 侵略性肿瘤特征，我们缺乏有关transtubal扩散和的预后影响的经验数据 这种关系是否通过其他肿瘤特征来改变。拟议的总体目标 研究是为了确定腔内肿瘤细胞（ILTC）之间关系的精确估计。 对型号扩散的客观测量和临床结果，并评估是否合并 肿瘤特征提高了预测精度。为了实现我们的目标，我们将从五个大型的资源中汇集资源 学术医院。我们将收集存档的输卵管幻灯片的数字图像并进行病理 审查以确定1,429名子宫内膜癌患者的ILTC存在。这些信息将与 现有的临床数据以确定ILTC与生存结果之间的关系 组织学亚型和阶段（目标1）。我们还将检查添加ILTC是否可以改善预后 准确性（AIM 2）。我们已发表的飞行员数据的结果使我们期望ILTC的存在将与众不同 具有生存期，特别是在被诊断出患有浆液肿瘤或I期肿瘤的女性中。而且，我们期望 一旦修改了阶段以预测生存结果的预测准确性更高 ILTC状态。这项投资将是对transtubal蔓延对影响的首次驱动分析 子宫内膜癌的预后。我们的结果具有较高的翻译潜力，以提炼阶段标准和 改善风险分层，以更好地指导术后治疗决策并减少内术 癌症死亡率。