CANCER GENETICS NETWORK (CGN) OVARIAN SCREENING PILOT TRIAL IN HIGH RIS WOMEN

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 截至2006年7月2日： 尽管有新的疗法，卵巢癌患者的五年生存率在过去三十年中并没有显着变化。 然而，当在早期发现时，卵巢癌的生存率通常比在晚期发现时更好。 这项研究是一项卵巢癌筛查方案，使用称为CA 125的测试。 CA 125是FDA批准的用于检测已经患有卵巢癌的妇女的疾病复发的标志物。 这项研究的目的是确定CA 125是否有助于早期发现卵巢癌的妇女在卵巢癌的高风险，由于乳腺癌或卵巢癌的家族史，或遗传改变的基因称为BRCA 1和BRCA 2。 本研究的第二个目的是评估卵巢癌筛查对女性生活质量的影响。 这项研究是由美国国家癌症研究所（NCI）赞助的癌症遗传学网络（CGN）的一部分，将在两到三年的时间内评估研究参与者，测试CA 125的有效性。 参与该项目还将有助于识别高危妇女，以期及早发现卵巢癌。 如果这些检查的结果表明，该风险组中的患者将由其医生转诊进行超声检查、腹腔镜检查和/或手术。 初始摘要： 具有BRCA 1和BRCA 2突变的女性患卵巢癌的终生风险比没有这种突变的女性高10-20倍。即使在预防性手术后，妇女也可能发展为腹膜癌病，这种疾病在临床和组织学上与晚期卵巢癌相同。我们假设，对于卵巢癌高危女性，通过纵向CA 125测量和超声筛查卵巢癌或腹膜癌转移可能比目前的做法更早发现。这样的筛查试验也允许通过年龄和绝经状态初步估计卵巢癌的发病率。本试验有四个具体目的：1）确定前瞻性方案的可行性，并确定筛查的后勤问题及其在此框架内的解决方案; 2）建立CA 125值随时间变化的正常范围和分布，并根据绝经前/绝经后状态，ERT使用（是/否）和预防性卵巢切除术（是/否）进行亚分类; 3）获得ROCA（risk of ovarian cancer algorithm）的特异性和阳性预测值的估计值，适用于设计高危妇女中卵巢癌筛查的确定性试验：4）建立纵向血清和血浆生物库，用于回顾性评价与遗传性卵巢癌和乳腺癌风险特别相关的其他有前途的生物标志物。 CGN卵巢筛查试验是一项多中心试验，招募来自卵巢癌高风险家庭的妇女。该设计是一项前瞻性单臂研究，根据基线和每三个月间隔测量的血液中肿瘤标志物CA 125水平进行决策。受试者将在12个月的时间内招募，筛选至少1年，如果在招募期开始时招募，则最多筛选2年，并再随访1年进行癌症临床诊断。对于每个新的CA 125测量值，将计算ROCA并存储在CGN临床数据库中。ROCA根据年龄、家族史和纵向CA 125值计算患卵巢癌的风险，然后根据风险水平对受试者进行分类。一旦获得卵巢癌风险，将立即通过电子邮件将CA 125值和采取的措施发送给研究中心项目经理。行动的选择将取决于风险水平，研究中心将负责联系患者。还将要求受试者完成基线问卷，询问健康史、环境暴露和家族史，以及每次抽血时关于受试者自上次CA 125检测以来健康状况变化的简要问卷。 GCRC将对研究受试者进行抽血，并在每次抽血后24小时内旋转样本。GCRC还将在-70 ° C下储存样本，直至每周运送至中心实验室。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As of 2/07/06: Despite new therapies, the five-year survival rate for patients with ovarian cancer has not changed significantly over the past thirty years. When detected in early stages, however, survival from ovarian cancer is usually better than when it is detected at later stages. This study is an ovarian cancer screening protocol, using a test called CA125. CA125 is an FDA approved marker for detecting recurrence of disease in women who have already had ovarian cancer. This research study aims to determine if CA125 is helpful in the early detection of ovarian cancer among women at high-risk for ovarian cancer due to a family history of breast or ovarian cancer, or an inherited alteration in genes called BRCA1 and BRCA2. A secondary goal of this study is to assess the impact of ovarian cancer screening on women's quality of life. This study is part of the Cancer Genetics Network (CGN) sponsored by the National Cancer Institute (NCI) and will evaluate study participants over a two to three-year period testing the effectiveness of CA125. Participation in this project will also help identify women in a high-risk category with the hope of detecting ovarian cancer early. Patients in this risk group will be referred by their physicians for ultrasound, laparascopy and/or surgery if it is indicated by the results of these tests. Initial Abstract: Women with a BRCA1 and BRCA2 mutation have an increased lifetime risk for ovarian cancer of 10-20 fold higher than women without such mutations. Even after prophylactic surgery women may develop peritoneal carcinomatosis, a disease clinically and histologically identical to late stage ovarian cancer. We hypothesize that for women with a high risk of developing ovarian cancer, screening for ovarian cancer or peritoneal carcinomatosis with longitudinal CA125 measurements and ultrasound may permit earlier detection than current practice. Such a screening trial would also permit initial estimation of the incidence of ovarian cancer by age and menopausal status. There are four specific aims of this trial: 1) determine the feasibility of prospective programs, and identify the logistical issues of screening and their solutions within this framework; 2) establish normal ranges and distribution within and between high risk women for CA125 values over time, with sub-classification by pre/post-menopausal status, ERT usage (yes/no), and prophylactic oophorectomy (yes/no); 3) obtain estimates of the specificity and positive predictive value of ROCA (risk of ovarian cancer algorithm)suitable for desgning a definitve trial of screening for ovarian cancer in high risk women; 4) establish a longitudinal serum and plasma bio-repository for retrospective evaluation of other promising biomarkers with special relevance to inherited ovarian and breast cancer risk. The CGN ovarian screening trial is a mulit-center trial, recruiting women from families with high risk for ovarian cancer. The design is a prospective one=armed study with decision making based on the tumor marker CA125 levels measured in blood at baseline and every three-moth interval. Subjects will be recruited over a period of twelve moths, screened for at lease one year and for up to two years if recruited at the beginning of the recruitment period, and followed for clinical diagnosis of cancer for an additional year. For each new CA125 measurement, the ROCA will be calculated and stored in the CGN clinical database. ROCA calculates the risk of having ovarian cancer based on age, family history, and longitudinal CA125 values and then triages the subject according to the level of risk. The CA125 value and the action to be taken will be emailed to the site project manager immediately upon availability of the risk of having ovarian cancer. The choice of action will depend on the level of risk, and the site will be responsible for contacting the patient. Subjects will also be asked to complete a baseline questionnaire asking about health history, environmental exposures, and family history, as well as brief questionnaires at each blood draw regarding any changes in the subject's health since the last CA125 test. The GCRC will perform blood draws on study participants, and will spin samples within 24 hours of each draw. The GCRC will also store samples at -70o C until shipping to the central laboratory every week.