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: 10544781
• 负责人: Jennifer Kehlet Barton
• 金额: $ 75.19万
• 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/10544781
• 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.

卵巢癌的一个中心问题是晚期诊断，这导致5年生存率急剧下降