Ovarian cancer study
GOG-0199: The National Ovarian Cancer Prevention and Early Detection Study
by Sue Friedman
GOG-0199 is a unique collaboration between the National Cancer Institute, the Gynecologic Oncology Group (GOG), and the NCI sponsored Cancer Genetics Network to study women who are at increased genetic risk for ovarian cancer. The research design is a two-arm, prospective, nonrandomized study. “Two-arm” means researchers are comparing high-risk women in two groups: those who elected risk-reducing salpingo-oophorectomy (RRSO) and those who chose high-risk screening for ovarian cancer. “Prospective” means that these women are being followed from the time of enrollment forward—in the case of GOG-0199, for a period of five years from the time they joined the study. “Nonrandomized” means that the participants chose which group they would be assigned to (surgery or surveillance) based on their risk-management plan. Women who chose surveillance were followed with a new ovarian cancer screening strategy, the “Risk of Ovarian Cancer Algorithm,” aka ROCA, and had CA-125 levels drawn every three months. Instead of using one annual CA-125 level compared against a “normal range” of test results, ROCA looked at changes in the levels of CA- 125 over time as the basis for deciding whether or not additional tests were needed to look for ovarian cancer.
The study was designed to answer the following important questions:
- Does ROCA have potential for improving ovarian cancer screening?
- How is ROCA affected by other characteristics of the women being screened, such as age, prior pregnancy, and various medications?
- Are there new protein or chemical markers detectable in the collected blood samples which might be more effective than CA-125 in detecting early ovarian cancer?
GOG-0199 completed enrollment in November 2007, with 1,000 women in the RRSO arm and 1,600 women in the screening arm. Follow- up ended in November 2011. Final analysis is underway to examine the Primary Study Endpoints, which include comparing women in each arm of the study for:
- cancer incidence
- medical decision making
- performance characteristics of the ROCA algorithm in detecting ovarian cancer
Greene MH, Piedmonte M, Alberts D, et al. “A prospective study of risk reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: Design and baseline characteristics–A Gynecologic Oncology Group Study.” Cancer Epidemiology Biomarkers & Prevention vol. 17, no. 3 (2008): 594-604.
Skates SL, Mai P, Horick NK, et al. “Large prospective study of ovarian cancer screening in high-risk women: CA125 cut-point defined by menopausal status.” Cancer Prevention Research vol. 4, no. 9 (2011): 1401-8.
The BRCA mutation status of all participants is now known, and central review of the surgical specimens from risk-reducing salpingo-oophorectomies has been completed. Researchers have collected a valuable repository of DNA, serum, plasma, and tissue samples from high-risk women to answer important questions about the development of ovarian cancer. The tissue specimens collected during preventive surgery include normal tissue from women who were cancer-free and malignant tissue from women whose cancer was found at the time of their preventive surgery.
Another focus for GOG-0199 relates to its membership in CIMBA (Consortium of Investigators of Modifiers of BRCA1/2), an international collaboration of 30 research groups that has assembled a collection of 30,000 BRCA mutation carriers to look for new genes that modify risk in BRCA mutation carriers. GOG- 0199 has contributed samples to five CIMBA projects looking for candidate genes that influence cancer risk. Two of the most important observations to date are: (1) 12 genetic variants that are known to modify sporadic breast cancer risk are now confirmed to play a similar role in BRCA-related breast cancer risk; (2) several new locations of gene variants which may affect risk for ovarian cancer in BRCA mutation carriers have been identified. Over time, researchers expect these studies will help to improve and individualize BRCA-related cancer risk assessment and help women make risk management decisions.
Ongoing analyses include:
- performance characteristics of the ROCA screening algorithm
- histopathology of 1,000 RRSO surgical specimens (both ovaries and fallopian tubes) to better understand how ovarian cancer develops
- factors influencing the choice between RRSO and screening among high-risk women
- baseline quality-of-life profiles of women electing RRSO and screening
Stay tuned for updates on results when they are available.
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