Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival: An Integrative Approach

摘要 上皮性卵巢癌(EOC)是女性癌症死亡的第五大原因。与非 西班牙裔白人(Nhw)、非裔美国人(Aa)女性在EOC后的存活率要差得多。 诊断，正如我们已经发现的，这可能部分是由于再生障碍性贫血妇女不太可能接受标准的- 护理治疗，更有可能减少化疗剂量，即使在平等获得医疗保健的情况下也是如此 系统。然而，这些因素并不能完全解释AA之间的生存差距，而且， 对其他群体(如西班牙裔和亚洲人/太平洋岛民)知之甚少，尽管有一些 有证据表明，拉美裔女性的存活率也更差。此外，新出现的证据表明，种族 分子亚型分布的差异。我们建议进行第一次整合，细胞到社会 评价不同水平的因素对卵巢癌治疗和生存结果的影响。 我们将汇集约4600个EOC案例，其中包括约280个AA、约520个西班牙裔、约730个API和 2000年至2023年期间，约有2980名nhw妇女在北加州凯撒永久医院(KPNC)确诊。 KPNC拥有悠久的电子临床数据库，完整的病理标本存储，长期 会员的保留率，以及社会人口、临床和社区的显著差异 种族/民族之间的特点。我们将进行集中病理检查，根据组织类型进行分类 最近的黄金标准世卫组织标准，并将进行图表审查，以获取没有数据 在电子设备上。我们将研究接受治疗的种族/民族差异、复发和 生存(总体和特定于EOC)，包括通过链接到以下数据的社区社会压力源 种族隔离、结构性种族主义、族裔飞地和地理上的医疗可及性、保健系统和 病人层面的因素。在800名患有高级别浆液性卵巢癌的妇女中(NHW、AA、西班牙裔和API各200人)， 我们还将表征基因表达亚型(到目前为止，几乎只在nhw妇女中进行研究)， 确定攻击性亚型的相对分布是否对观察到的生存差异有贡献。 我们将在自我报告的种族/族裔和遗传血统的背景下审查这些因素。 我们全面综合的方法来检查患者、医疗保健、社会 背景、生物因素将为平等机会持续存在的种族差异提供独特的见解 生死存亡。KPNC设置提供了检查这些因素的机会，同时通过以下方式最大限度地减少混淆 保险状况的已知贡献，利用丰富的临床数据库来调查和控制 详细的预后变量，避免生存偏差。对于平机会来说，这项拟议的研究是前所未有的 跨学科的性质、样本量和多种族人口，并将成为 未来的研究涉及降低EoC存活率差异的多层次因素。

ABSTRACT Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths in women. Compared to non- Hispanic white (NHW) women, African American (AA) women have much poorer survival after an EOC diagnosis, which, as we have found, may be in part due to AA women being less likely to receive standard-of- care therapy, and more likely to have chemotherapy dose reduction, even within an equal-access healthcare system. However, these factors do not completely explain survival disparities among AAs, and furthermore, little is known about other groups (e.g., Hispanics and Asians/Pacific Islanders (API)), although there is some evidence that Hispanic women also experience worse survival. Moreover, emerging evidence suggests racial differences in molecular subtype distribution. We propose to conduct the first integrative, cells-to-society evaluation of the interplay among multilevel factors on disparities in EOC treatment and survival outcomes. We will assemble a cohort of ~4,600 EOC cases, including ~280 AA, ~520 Hispanic, ~730 API, and ~2,980 NHW women diagnosed at Kaiser Permanente Northern California (KPNC) between 2000 and 2023. KPNC has longstanding electronic clinical databases, complete pathology specimen storage, long-term retention of members, and substantial variability in sociodemographic, clinical, and neighborhood characteristics among races/ethnicities. We will perform centralized pathology review to classify histotypes by the recent gold standard WHO criteria, and will conduct chart review to capture data that are not available electronically. We will examine determinants of racial/ethnic differences in treatment received, recurrence, and survival (overall and EOC-specific), including neighborhood social stressors through linkage to data on segregation, structural racism, ethnic enclaves, and geographic medical accessibility, health care system and patient-level factors. In 800 women (200 each of NHW, AA, Hispanic, and API) with high grade serous EOC, we will also characterize gene expression subtypes (to date studied almost exclusively in NHW women), to identify whether the relative distribution of aggressive subtypes contributes to the observed survival disparities. We will examine these factors in the context of both self-reported race/ethnicity and genetic ancestry. Our comprehensive integrative approach to examine the interplay among patient, health care, social contextual, and biological factors will provide unique insights into the persistent racial disparities in EOC survival. The KPNC setting provides the opportunity to examine these factors while minimizing confounding by the known contribution of insurance status, leveraging rich clinical databases to investigate and control for detailed prognostic variables, and avoiding survival bias. For EOC, this proposed study is unprecedented in its transdisciplinary nature, sample size, and multi-ethnic population, and will serve as a unique resource for future research related to multilevel factors to reduce EOC survival disparities.