BMED Project 1 Group: Eric Sood Hamza Darb Jean Wall Matt Richner Regina Chang Mickael Gueye OVARIAN CANCER SCREENING PROBLEM

Ovarian cancer Survival improved when cancer detected in early stage Survival rate for stage I disease is about 90% and for stage II about 70%. Women with OC+BC Hereditary background Women over age 50 account for ~80% of all cases (avg. age at diagnosis is 61) early menarche, nulliparity or age >30 at first child- bearing, and late menopause Prolonged use of Clomid, especially without achieving pregnancy Paul D. DePriest & Christopher P. DeSimone, Journal of Clinical Oncology,2004 Who should be concerned?

Signs & Symptoms Ovarian Cancer (Ovaraian Cancer) -Vague and non-specific – Abdominal bloating – Indigestion – Uterine bleeding – Pelvic fullness – Pain

Stages A5B

Symptoms Index & Family History ● 1.4% lifetime risk with no history ● Women are considered high risk have: ● first degree relative with ovarian cancer and/or early breast cancer (risk increases with quantity) ● family with both cancers or male breast cancer Sensitivity ● 79.5% for advanced-stage disease. Specificity ● 86.7% (same sen.) for women age <50 years. Not the most sensitive and specific test, but the easiest to perform on general population and low risk

Diagnostic tools & Screening methods History (BRCA) Pelvic Exam (including rectal) Transvaginal Ultrasound – detection of masses and mass characteristics Tumor markers – CA-125, HE4 CT – assess spread to LN, pelvic and abdominal structures MRI – best for distinguishing malignant from benign tumors

CA-125 Accuracy 83% sensitivity, 99.7% specificity 16% PPV depending on if your body secretes the protein1 1Ovarian Cancer screening UCLA School of Medicine Cost Between $60-$100 Definition A cancer marker, a protein normally made by certain cells in the body including those of the uterine tubes, uterus, cervix, and the lining of the chest and abdominal cavities CA125 stands for cancer antigen 125.

HE4 The gene was initially identified in epithelialcells of human epididymis is fertility-related protein. A laboratory test to detect a protein called HE4, which is released into the blood by ovarian tumors.1 Fred Hutchinson Cancer Research Center; Seattle, WA

Combination Test When HE4 and CA-125 are combined the effectiveness of screening is higher. The sensitivity is 76.7% and the specificity is 95%1. The cost is about $60- $200. The best thing about HE4 and CA-125 was that it detects 45.9% of Stage I ovarian cancer. University of Madison 81%

Ultrasound TVUS underway has reported sensivity 81% & specificity 98.9% Major limitations are poor PPV 20% in asymptomatic women and inability to detect malignances when ovaries are normal size improved by used Color Doppler Cost $75- $200 D. DePriest &DeSimone, Clinical Oncology,2004

General Info BRCA: short for breast cancer 1 and % of population has this genetic deformity Statistics Sensitivity: 93% Specificity: 17% PPV: 75% How it Works A blood sample is to analyze the DNA in white blood A doctor can determine whether or not any mutations are present in the gene This is a very time consuming and labor intensive procedure Total Cost of BRCA 1 & 2 tests: $3280-$3480 Interpretation of Results Takes on average 3-4 weeks for BRCA 1 & 2 results to be received. Takes on average 1-4 weeks for BRCA (Ashkenazi Mutations) results to be received. Blood Tests BRCA 1 & 2

Ways to improved…? Current Plan Hirosaki & University of Kentucky screening algorithm

Proposed Plan

After math Sensitivity: 95.24% Specificity: 99.99% Positive Predicted Value: 76.92%

Additional Citations David E. Cohn, N. C. H., Stephen P. Povoski, Leigh G. Seamon, William B. Farrar, Edward W. Martin Jr. (2008). "Novel perioperative imaging with 18F-FDG PET/CT and intraoperative 18F-FDG detection using a handheld gamma probe in recurrent ovarian cancer." Gynecologic Oncology(110): David H Geho, C. D. J., Emanuel F Petricoin and Lance A Liotta (2006). "Nanoparticles: potential biomarker harvesters." Current Opinion in Chemical Biology(10): 56–61. Irene Visintin, Z. F., Gary Longton, David C. Ward, Ayesha B. Alvero, Yinglei Lai, Jeannette Tenthorey, Aliza Leiser, Ruben Flores-Saaib, Herbert Yu, Masoud Azori, Thomas Rutherford, Peter E. Schwartz and Gil Mor (2008). "Diagnostic Markers for Early Detection of Ovarian Cancer." Clinical Cancer Research 14(4): K. Maheedhar, M. S., Rani A, Bhat M.D., R. Malini, M. Sc, N.B. Prathima, M. Sc, Patil Keerthi, B. Sc and C. Murali Krishna, Ph.D. (2008). "Diagnosis of Ovarian Cancer by Raman Spectroscopy; A Pilot Study." Photomedicine and Laser Surgery 26(2):