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: 10314537
• 负责人: Jennifer Kehlet Barton
• 金额: $ 81.19万
• 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/10314537
• 关键词: Address; 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; Collection; Data; Detection; Development; Diagnosis; Disease; Early Detection Research Network; Early Diagnosis; Endoscopes; Endoscopy; Epithelial; Epithelial Cells; Epithelial ovarian cancer; Family; Fertility; Genetic; Goals; Gold; Greater sac of peritoneum; Health; High Risk Woman; Histology; Human; Hysterectomy; Image; Image Analysis; Imaging Techniques; Instruction; Lead; 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; Recording of previous events; Research; Resolution; Risk; 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; Tube; Woman; Work; base; 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

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，这会导致5年的存活率暴跌 低于50％。卵巢癌症状含糊不清，当前筛查通常不是 有效的。由于卵巢癌是如此致命，因此降低风险的salpingo-opophorortormo术（RRSO）通常是 推荐给有高风险的妇女；但是，RRSO具有生育能力和健康后果。现在 认为卵巢高级浆液性癌（HGSC）可能在输卵管（FTS）中开始为浆液 输卵管上皮内癌（ETIC），并且在转移之前可以检测到癌前变化 发生卵巢和腹膜腔。我们的初步数据表明，血清有重大变化 诊断前12-84个月，HGSC病例中的蛋白质生物标志物。此外，我们还表明了变化 发生在正常和癌性卵巢和FTS的多光谱荧光图像中，我们可以 建立一个薄的型室外镜，适合穿越子宫和FT进行成像和细胞收集。 我们将满足未满足的临床需求，对Stic和早期（I/II）卵巢的最小侵入性测试 癌症。目前，没有方法可以在超过12个月的时间内检测卵巢HGSC。 总体而言，我们的工作将满足最早可能在可能的阶段检测侵略性癌症的需求。我们的最初 目标人群是希望延迟或避免RRSO的卵巢癌高风险的女性。我们将结合 用微创肌镜检查进行光学成像和FT细胞的蛋白质标志物的血液筛查 收藏。我们的程序将在对经历双边salpingo-高风险的妇女的研究中进行测试。 子宫切除术进行卵巢切除术，这将使我们能够获得并比较测试结果与黄金标准 组织学。具体目的是： 1）开发和验证检测Stic和早期上皮卵巢癌的生物标志物。我们将有所改善 在我们现有的基于截止的算法上，新发现的标记也开发了基于速度的标记 生物标志物算法。诊断前12-84个月检测到疾病的算法将在 独立的，盲目的临床血液样本。 2）发展内窥镜成像和病原标记。我们将改善原型逆转镜 具有较高分辨率的多光谱成像和提高的细胞收集能力的系统。我们将发展 来自FT图像和收集的细胞的成像和成项标记物，并进行体内研究。 3）制定可起作用的临床策略，用于早期发现上皮卵巢癌。研究将是 在计划RRSO的高风险女性中表演。那些从我们的血液检查中测试阳性的人 在特定目标1中开发的组织将使其组织进行降生管镜检查。成像和致病数据将是 用于开发分类器，该分类器将与正常FT，Stic或 神秘的HGSC。