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: 10598251
• 负责人: Jennifer Kehlet Barton
• 金额: $ 3.45万
• 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/10598251
• 关键词: 3-Dimensional; Address; Algorithms; Arizona; Bilateral; Biological Markers; Blinded; Blood; Blood Screening; Blood Tests; Blood specimen; Cancerous; Carcinoma; Carcinoma in Situ; Catheters; Cells; Clinical; Clinical Research; Collection; Data; Detection; Diagnosis; Disease; Early Diagnosis; Endoscopes; Endoscopy; Epithelial ovarian cancer; Family suidae; Fertility; Flushing; Glass; Gold; Health; High Risk Woman; Histology; Human; Hysterectomy; Image; Laboratories; Lead; Lesion; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Mentors; Methods; Operative Surgical Procedures; Optics; Ovarian; Ovary; Performance; Printing; Procedures; Process; Property; Research; Research Proposals; Resolution; Risk; Saline; Salpingo-Oophorectomy; Sampling; Science; Screening for Ovarian Cancer; Serous; Serum Proteins; Students; Survival Rate; System; Techniques; Technology; Test Result; Testing; Thinness; Time; Tissues; Training; Tube; Universities; Work; base; blood-based biomarker; clinically actionable; college; design; fluorescence imaging; graduate student; imaging biomarker; improved; in vivo; lens; mechanical properties; minimally invasive; novel; optical imaging; parent grant; performance tests; pre-doctoral; protein biomarkers; prototype; screening; sensor; skills

PROJECT SUMMARY This application is to support a predoctoral graduate student, Ms. Dominique Galvez, through a diversity supplement to R01CA260399. Ms. Galvez will directly support and expand upon Specific Aim 2: Develop endoscopic imaging and pathomics markers, advancing progress as well as expanding her training. A central problem in ovarian cancer is late diagnosis, which causes the 5-year survival rate to plummet below 50%. 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). 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. 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 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.

项目摘要 这个应用程序是支持博士前的研究生，多米尼克·加尔维斯女士，通过多样性。 补充R 01 CA 260399。Galvez女士将直接支持和扩展具体目标2：发展 内窥镜成像和病理组学标记，推进进展以及扩大她的培训。 卵巢癌的一个中心问题是诊断晚，这导致5年生存率直线下降 低于50%。由于卵巢癌是如此致命，降低风险的输卵管卵巢切除术（RRSO）往往是 建议高危妇女使用;然而，RRSO会对生育和健康产生影响。现在 认为卵巢高级别浆液性癌（HGSC）可能开始于输卵管（FT）， 输卵管上皮内癌（STIC）。我们的初步数据表明，血清中有显着的变化， HGSC病例中的蛋白质生物标志物在诊断前12-84个月。此外，我们还表明， 发生在正常和癌性卵巢和FT的多光谱荧光图像标记中，我们可以 建立一个薄的输卵管镜适合穿越子宫和FT成像和细胞收集。 我们将解决STIC和早期（I/II期）卵巢癌的微创检测未满足的临床需求。 癌目前，没有方法能够检测提前时间超过12个月的卵巢HGSC。 总的来说，我们的工作将满足在尽可能早的阶段检测侵袭性癌症的需要。我们将 联合收割机将蛋白质标记物的血液筛查与用于光学成像和FT的微创输卵管镜检查相结合 细胞收集。我们的手术将在一项对接受双侧输卵管切除术的高危妇女的研究中进行测试- 卵巢切除术和子宫切除术，这将使我们能够获得并比较测试结果与金标准 组织学具体目标是： 1)开发和验证检测STIC和早期上皮性卵巢癌的生物标志物。完善 在我们现有的基于截断的算法与新发现的标记，以及开发一个基于速度 生物标记算法在诊断前12-84个月检测疾病的算法将在 一组独立的盲态临床血液样本。 2)开发内窥镜成像和病理学标记。我们将改进我们的原型falloposcope 系统具有更高的分辨率多光谱成像和改进的细胞收集能力。我们将开发 来自FT图像和收集的细胞的成像和核型标记，并进行初步体内研究。 3)制定一个可行的临床策略，早期发现上皮性卵巢癌。一项研究将 在计划RRSO的高风险女性中进行。那些血液检测呈阳性的人 让他们的组织接受输卵管镜检查成像和病理组学数据将用于开发分类器， 将其与正常FT、STIC或隐匿性HGSC的金标准组织学结果进行比较。