Outpatient Screening for Early-Stage High-Grade Serous Ovarian Cancer in Higher Risk Women

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Project Summary This year, over 22,000 women in the U.S. will be diagnosed with ovarian cancer (OvCa), and ~14,000 will die from this disease. Approximately 9,000 of these deaths occur from high-grade serous epithelial cancer (HGSC) primarily because of our inability to detect the disease in its early stages. OvCa accounts for 2.5% of all female cancer cases but 5% of deaths, resulting from the low HGSC survival rate as the majority of women are diagnosed with advanced disease that becomes resistant to chemotherapy. It is well known that timely detection of early-stage disease could improve 5-year survival rates to >90%, with a significant associated reduction in morbidity and mortality. Unfortunately, the biology, genetics, and life history of the disease have proven to be particularly frustrating in terms of development of a widely available, accurate, and cost-effective screening test. Our innovative approach to this unmet clinical need exploits the remarkable observation that the majority of HGSC does not originate in the ovary but rather in the fallopian tube (FT), with subsequent migration to the ovary. We have developed a micro-endoscope (falloposcope) with the high-resolution functional and structural imaging capabilities needed to identify early-stage HGSC at the 0.5-mm to 5-mm lesion size, when the impact on mortality could be profound. In this proposal, we will develop the clinical features needed (a) to allow the falloposcope to be used quickly, safely and effectively in an outpatient setting, and (b) to allow immediate clinical feedback to the patient in a manner analogous to colonoscopy or colposcopy. To achieve our goals, we propose to develop a mechanism to dock with and enter the ostia of the fallopian tubes (Specific Aim 1), such that this procedure can be performed by a single operator and ameliorate one of the primary obstacles to widespread clinical adoption of the device. In Specific Aim 2, we will develop a mechanism to deliver the endoscope to the distal FT. This will consist of an automated delivery system with pressure-sensitive feedback to ensure the safe delivery and recovery of the device, and the reproducible imaging conditions needed for validation of the screening test. Lastly, Specific Aim 3 will establish 90% specificity for outpatient-based screening. We will image surgical discard tissue from approximately 100 patients ex vivo, but in an otherwise clinically representative procedure, using samples from individuals with both benign conditions and risk-reducing surgeries. The imaging results will be correlated to gold-standard pathology to continue building the rigorous statistical foundation needed for a high negative predictive value on which to base the screening test. At the end of this Phase I application, we will be in a position to test our imaging device in a clinical setting as part of a Phase II proposal.