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- 西班牙裔白色（NHW）妇女、非洲裔美国人（AA）妇女在EOC后的生存率要差得多 诊断，其中，正如我们所发现的，可能部分是由于AA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 系统然而，这些因素并不能完全解释AA之间的生存差异，此外， 对其它组知之甚少（例如，西班牙裔和亚洲人/太平洋岛民（API）），尽管有一些 有证据表明西班牙裔女性的生存率也更低。此外，新出现的证据表明， 分子亚型分布的差异。我们建议进行第一次综合性的，细胞对社会的 评价多水平因素对EOC治疗和生存结局差异的相互作用。 我们将收集约4，600例EOC病例的队列，包括约280例AA，约520例西班牙裔，约730例API， 2000年至2023年期间，在Kaiser Permanente北方加州（KPNC）诊断出约2，980名NHW女性。 KPNC拥有长期的电子临床数据库，完整的病理标本存储，长期 成员的保留，以及社会人口统计学，临床和邻里的实质性变化 种族/民族之间的特征。我们将进行集中病理学审查，通过以下方式对组织型进行分类： 并将进行图表审查，以获取无法获得的数据 电子方式我们将研究种族/民族差异的决定因素，包括接受的治疗、复发和 生存率（总体和EOC特异性），包括通过与以下数据联系的邻里社会压力因素 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 患者层面的因素。在800名患有高级别浆液性EOC的女性（NHW、AA、西班牙裔和API各200名）中， 我们还将描述基因表达亚型（迄今为止几乎只在NHW女性中研究）， 确定侵袭性亚型的相对分布是否有助于观察到的生存差异。 我们将在自我报告的种族/民族和遗传祖先的背景下研究这些因素。 我们全面的综合方法来检查病人，医疗保健，社会 背景、生物因素将为平等机会委员会中持续存在的种族差异提供独特的见解 生存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，避免生存偏倚。对平机会来说，这项建议研究是前所未有的， 跨学科性质，样本量和多种族人口，并将作为一个独特的资源， 未来的研究相关的多层次因素，以减少EOC生存差距。

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.