Ovarian Cancer Detection with Blood- and Imaging-Based Biomarkers

使用基于血液和成像的生物标志物检测卵巢癌

• 批准号: 10737827
• 负责人: Jennifer Kehlet Barton
• 金额: $ 6.26万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737827
• 关键词: Algorithms; Bilateral; Biological Markers; Blinded; Blood; Blood Proteins; Blood Screening; Blood Tests; Blood specimen; CA-125 Antigen; Cancer Etiology; Cancerous; Carcinoma; Carcinoma in Situ; Cells; Cessation of life; Clinical; Collecting Cell; Collection; Data; Detection; Development; Diagnosis; Disease; Early Detection Research Network; Early Diagnosis; Endoscopes; Endoscopy; Epithelial Cells; Epithelial ovarian cancer; Epithelium; Family; Fertility; Genetic; Goals; Greater sac of peritoneum; Health; High Risk Woman; Histology; Human; Hysterectomy; Image; Image Analysis; Imaging Techniques; Instruction; Lead; Learning; Lesion; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Metastatic Malignant Neoplasm to the Ovary; Methods; Morbidity - disease rate; Neoplasm Metastasis; Operative Surgical Procedures; Ovarian; Ovarian Serous Adenocarcinoma; Ovary; Patients; Pilot Projects; Predictive Value; Procedures; Proteomics; Recommendation; Recording of previous events; Research; Resolution; Risk; Risk Reduction; Salpingo-Oophorectomy; Sampling; Screening for Ovarian Cancer; Sensitivity and Specificity; Serous; Serum; Serum Markers; Serum Proteins; Survival Rate; Symptoms; System; Target Populations; Techniques; Technology; Test Result; Testing; Thinness; Time; Tissues; Transvaginal Ultrasound; Woman; Work; biomarker validation; blood-based biomarker; cell preparation; classification algorithm; clinically actionable; fluorescence imaging; high resolution imaging; imaging biomarker; improved; in vitro Model; in vivo; miniaturize; minimally invasive; mortality; optical imaging; premalignant; protein biomarkers; prototype; screening; spectrograph

A central problem in ovarian cancer is late diagnosis, which causes the 5-year survival rate to plummet below 50%. Ovarian cancer symptoms are vague and nonspecific, and current screening is generally not effective. Because ovarian cancer is so deadly, risk-reducing salpingo-oophorectomy (RRSO) is often recommended for women at high risk; however, RRSO has fertility and health consequences. It is now believed that ovarian high-grade serous carcinoma (HGSC) may begin in the fallopian tubes (FTs) as serous tubal intraepithelial carcinoma (STIC), and that precancerous changes are detectable before metastasis to the ovary and peritoneal cavity occurs. Our preliminary data indicate that there are significant changes in serum protein biomarkers in HGSC cases 12-84 months prior to diagnosis. Further, we have also shown that changes occur in multispectral fluorescence image markers of normal and cancerous ovaries and FTs, and that we can build a thin falloposcope suitable for traversing the uterus and FT for imaging and cell collection. We will address the unmet clinical need for a minimally invasive test for STIC and early (stage I/II) ovarian cancer. Currently, no methods enable the detection of ovarian HGSC with a lead time of more than 12 months. Overall, our work will meet the need to detect aggressive cancers at the earliest possible stage. Our initial target population is women at high risk for ovarian cancer who wish to delay or avoid RRSO. We will combine blood screening for protein markers with a minimally invasive falloposcopy for optical imaging and FT cell collection. Our procedure will be tested in a study of women at high risk undergoing bilateral salpingo- oophorectomy with hysterectomy, which will enable us to obtain and compare test results to gold standard histology. The specific aims are to: 1) Develop and validate biomarkers that detect STIC and early epithelial ovarian cancer. We will improve upon our existing cut-off based algorithm with newly-discovered markers as well develop a velocity-based biomarker algorithm. The algorithm that detects disease 12-84 months prior to diagnosis will be confirmed in an independent, blinded set of clinical blood samples. 2) Develop endoscopic imaging and pathomics markers. We will improve our prototype falloposcope system with higher resolution multispectral imaging and improved cell collection ability. We will develop imaging and karyometric markers from the FT images and the cells collected, and perform a pilot in vivo study. 3) Develop an actionable clinical strategy for early detection of epithelial ovarian cancer. A study will be performed in women at high risk who are planning a RRSO. Those who test positive from our blood test developed in Specific Aim 1 will have their tissue undergo a falloposcopy. Imaging and pathomics data will be used to develop a classifier, which will be compared to gold standard histology findings of normal FT, STIC, or occult HGSC.

卵巢癌的一个核心问题是晚期诊断，导致 5 年生存率直线下降 低于50%。卵巢癌症状模糊且非特异性，目前筛查一般不 有效的。由于卵巢癌非常致命，因此通常需要降低风险的输卵管卵巢切除术 (RRSO) 推荐给高危女性；然而，RRSO 会对生育和健康产生影响。现在是 认为卵巢高级别浆液性癌（HGSC）可能始于输卵管（FT），呈浆液性 输卵管上皮内癌（STIC），并且在转移到输卵管之前可以检测到癌前变化 卵巢和腹膜腔发生。我们的初步数据表明血清有显着变化 诊断前 12-84 个月 HGSC 病例的蛋白质生物标志物。此外，我们还表明，变化 发生在正常和癌变卵巢和 FT 的多光谱荧光图像标记中，我们可以 构建适合穿过子宫的薄型输卵管镜和 FT 进行成像和细胞采集。 我们将解决 STIC 和早期（I/II 期）卵巢微创检测未得到满足的临床需求 癌症。目前，还没有任何方法能够检测卵巢 HGSC，且周期超过 12 个月。 总的来说，我们的工作将满足尽早检测侵袭性癌症的需要。我们最初的 目标人群是希望推迟或避免 RRSO 的卵巢癌高危女性。我们将结合 使用光学成像和 FT 细胞微创输卵管镜检查进行血液蛋白质标记物筛查 收藏。我们的程序将在一项对接受双侧输卵管手术的高风险女性的研究中进行测试 卵巢切除术和子宫切除术，这将使我们能够获得测试结果并将其与金标准进行比较 组织学。具体目标是： 1) 开发并验证检测 STIC 和早期上皮性卵巢癌的生物标志物。我们会改进 基于我们现有的基于截止的算法和新发现的标记，以及开发基于速度的 生物标记算法。在诊断前 12-84 个月检测疾病的算法将在 一组独立、盲法的临床血液样本。 2) 开发内窥镜成像和病理组学标志物。我们将改进我们的输卵管原型机 系统具有更高分辨率的多光谱成像和改进的细胞收集能力。我们将开发 从 FT 图像和收集的细胞中进行成像和核分析标记，并进行体内试验研究。 3) 制定可行的临床策略以早期检测上皮性卵巢癌。一项研究将是 在计划 RRSO 的高危女性中进行。那些在我们的血液检测中呈阳性的人 具体目标 1 中开发的将对其组织进行输卵管镜检查。影像学和病理学数据将 用于开发分类器，该分类器将与正常 FT、STIC 或 神秘的 HGSC。