This year, over 22,000 women in the U.S. will be diagnosed with ovarian cancer (OvCa), and ~14,000 will diefrom 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 femalecancer cases but 5% of deaths, resulting from the low HGSC survival rate as the majority of women arediagnosed with advanced disease that becomes resistant to chemotherapy. It is well known that timely detectionof early-stage disease could improve 5-year survival rates to >90%, with a significant associated reduction inmorbidity and mortality. Unfortunately, the biology, genetics, and life history of the disease have proven to beparticularly 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 ofHGSC does not originate in the ovary but rather in the fallopian tube (FT), with subsequent migration to theovary. We have developed a micro-endoscope (falloposcope) with the high-resolution functional and structuralimaging capabilities needed to identify early-stage HGSC at the 0.5-mm to 5-mm lesion size, when the impacton 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 amanner analogous to colonoscopy or colposcopy. To achieve our goals, we propose to develop a mechanism todock with and enter the ostia of the fallopian tubes (Specific Aim 1), such that this procedure can be performedby 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 anautomated delivery system with pressure-sensitive feedback to ensure the safe delivery and recovery of thedevice, and the reproducible imaging conditions needed for validation of the screening test. Lastly, Specific Aim3 will establish 90% specificity for outpatient-based screening. We will image surgical discard tissue fromapproximately 100 patients ex vivo, but in an otherwise clinically representative procedure, using samples fromindividuals with both benign conditions and risk-reducing surgeries. The imaging results will be correlated togold-standard pathology to continue building the rigorous statistical foundation needed for a high negativepredictive value on which to base the screening test. At the end of this Phase I application, we will be in a positionto test our imaging device in a clinical setting as part of a Phase II proposal. Project Narrative
Over 22,000 women in the U.S. and 10 times that worldwide will be diagnosed this year with ovarian cancer,
and nearly 2 in 3 will die primarily because of our inability to detect early-stage disease; however, early detection
could increase survival and quality of life. This proposal will develop an outpatient-based screening test capable
of finding tumors of only a few millimeters in size, small enough that preventative measures can increase the
chance of patient survival to >90%. Our technique has the long-term potential to reduce mortality from the most
aggressive form of this deadly cancer by half. Adoption ; Algorithms ; Arizona ; Dysbarism ; Barotrauma ; Biology ; Biopsy ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Carcinoma ; Epithelial cancer ; Malignant Epithelial Neoplasms ; Malignant Epithelial Tumors ; epithelial carcinoma ; Malignant neoplasm of cervix uteri ; Cervical Cancer ; Cervix Cancer ; Malignant Cervical Neoplasm ; Malignant Cervical Tumor ; Malignant Neoplasm of the Cervix ; Malignant Tumor of the Cervix ; Malignant Tumor of the Cervix Uteri ; Malignant Uterine Cervix Neoplasm ; Malignant Uterine Cervix Tumor ; Uterine Cervix Cancer ; Cilia ; Colonoscopy ; Colposcopy ; Cessation of life ; Death ; Diagnosis ; Disease ; Disorder ; Endoscopes ; Endoscopy ; endoscopic imaging ; Mammalian Oviducts ; Fallopian Tubes ; Salpinx ; Uterine Tubes ; oviduct ; Family ; Feedback ; Female ; Foundations ; Goals ; Gold ; Histology ; Recording of previous events ; History ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Morbidity - disease rate ; Morbidity ; mortality ; Mucous body substance ; Mucus ; mucous ; New York ; Optics ; optical ; Outpatients ; Out-patients ; Ovary ; Pathology ; Patient Schedules ; Patients ; Peritoneum ; Polymers ; pressure ; Quality of life ; QOL ; Risk ; Salpingo-Oophorectomy ; Specificity ; Survival Rate ; Technology ; Testing ; Time ; Tissues ; Body Tissues ; X-Ray Computed Tomography ; CAT scan ; CT X Ray ; CT Xray ; CT imaging ; CT scan ; Computed Tomography ; Tomodensitometry ; X-Ray CAT Scan ; X-Ray Computerized Tomography ; Xray CAT scan ; Xray Computed Tomography ; Xray computerized tomography ; catscan ; computed axial tomography ; computer tomography ; computerized axial tomography ; computerized tomography ; Ultrasonography ; Echography ; Echotomography ; Medical Ultrasound ; Ultrasonic Imaging ; Ultrasonogram ; Ultrasound Diagnosis ; Ultrasound Medical Imaging ; Ultrasound Test ; diagnostic ultrasound ; sonogram ; sonography ; sound measurement ; ultrasound ; ultrasound imaging ; ultrasound scanning ; Universities ; Woman ; Pap smear ; Pap Test ; Pap screening ; Papanicolaou Smear ; Papanicolaou Test ; Imaging Techniques ; Imaging Procedures ; Imaging Technics ; Malignant neoplasm of fallopian tube ; Fallopian Tube Cancer ; Malignant fallopian tube tumor ; Tube ; base ; improved ; Procedures ; Screening for cancer ; Cancer Screening for Patients ; early cancer detection ; Transvaginal Ultrasound ; Ovarian ; Distal ; Site ; Benign ; Clinical ; Phase ; Histologic ; Histologically ; Germ-Line Mutation ; Germline Mutation ; Hereditary Mutation ; Ensure ; Evaluation ; Lesion ; Epithelial ; Individual ; Recovery ; Bilateral ; High Risk Woman ; women at high risk ; Collaborations ; Genetic ; Presbyterians ; Presbyterian Church ; Diagnostic ; Investigation ; millimeter ; Complex ; Serous ; Slide ; prophylactic ; Techniques ; System ; Location ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; Cancer Induction ; carcinogenesis ; early detection ; Early Diagnosis ; Performance ; life history ; cohort ; Histopathology ; Structure ; advanced illness ; advanced disease ; disease risk ; disorder risk ; Devices ; Colon Cancer ; Colonic Carcinoma ; cancer in the colon ; Colon Carcinoma ; Abscission ; Extirpation ; Removal ; Surgical Removal ; resection ; Excision ; Position ; Positioning Attribute ; Modeling ; Sampling ; Adverse Experience ; Adverse event ; Doppler OCT ; OCT Tomography ; optical Doppler tomography ; optical coherence Doppler tomography ; Optical Coherence Tomography ; intra-operative imaging ; intraoperative imaging ; surgical imaging ; Image-Guided Surgery ; Malignant Ovarian Neoplasm ; Malignant Ovarian Tumor ; Malignant Tumor of the Ovary ; Ovary Cancer ; ovarian cancer ; Malignant neoplasm of ovary ; Pathologic Constriction ; Pathological Constriction ; Stenosis ; Diameter ; Caliber ; Premalignant Change ; Symptoms ; Detection ; Imaging Instrument ; Imaging Tool ; Imaging Device ; intraepithelial ; Predictive Value ; precancerous ; premalignant ; Reproducibility ; Resolution ; in vivo ; Epigenetic Process ; Epigenetic ; Epigenetic Change ; Epigenetic Mechanism ; Validation ; Docking ; follow-up ; Active Follow-up ; active followup ; follow up ; followed up ; followup ; Development ; developmental ; point of care ; Image ; imaging ; cost ; optical imaging ; optic imaging ; design ; designing ; cost effective ; migration ; innovation ; innovate ; innovative ; Resistance ; resistant ; Cancerous ; chemotherapy ; tumor ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; screening ; imaging system ; imaging biomarker ; imaging marker ; imaging-based biological marker ; imaging-based biomarker ; imaging-based marker ; Preventive measure ; Preventative measure ; microendoscope ; endomicrosope ; imaging capabilities ; early screening ; routine screening ; annual screening ;
