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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。截至2006年2月7日：尽管有新的治疗方法，卵巢癌患者的5年生存率在过去的30年里并没有明显的变化。然而，如果在早期发现，卵巢癌的生存率通常比在晚期发现要好。这项研究是一项卵巢癌筛查方案，使用一种叫做CA125的测试。CA125是FDA批准的用于检测已经患有卵巢癌的妇女疾病复发的标志物。这项研究的目的是确定CA125是否有助于早期发现由于乳腺癌或卵巢癌家族史或BRCA1和BRCA2基因遗传改变而具有卵巢癌高风险的女性的卵巢癌。本研究的第二个目的是评估卵巢癌筛查对妇女生活质量的影响。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CA125的有效性。参与这一项目还将有助于确定高风险类别的妇女，以期及早发现卵巢癌。如果这些检查结果表明，这一危险群体的患者将由他们的医生转介进行超声、腹腔镜检查和/或手术。摘要：携带BRCA1和BRCA2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，这是一种临床和组织学上与晚期卵巢癌相同的疾病。我们假设，对于患卵巢癌的高风险妇女，通过纵向CA125测量和超声筛查卵巢癌或腹膜癌可能比目前的做法更早发现。这样的筛选试验还可以根据年龄和绝经状态初步估计卵巢癌的发病率。该试验有四个具体目标：1)确定前瞻性方案的可行性，并在此框架内确定筛选的后勤问题及其解决方案；2)建立CA125值在高危女性内部和之间随时间的正常范围和分布，并根据绝经前/绝经后状态、ERT使用情况（是/否）和预防性卵巢切除术（是/否）进行分类；3)获得适合设计明确的高风险女性卵巢癌筛查试验的ROCA （risk of ovarian cancer algorithm）特异性和阳性预测值的估计；4)建立纵向血清和血浆生物信息库，用于回顾性评估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，招募来自卵巢癌高危家庭的女性。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CA125水平做出决策。受试者将在12个月的时间内被招募，筛选至少一年，如果在招募期开始时被招募，筛选最长可达两年，并在另外一年进行癌症临床诊断。对于每一个新的CA125测量，ROCA将被计算并存储在CGN临床数据库中。ROCA根据年龄、家族史和纵向CA125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。CA125值和应采取的措施将在发现卵巢癌风险后立即通过电子邮件发送给现场项目经理。行动的选择将取决于风险的程度，该网站将负责与患者联系。受试者还将被要求完成一份关于健康史、环境暴露和家族史的基线问卷，以及每次抽血时关于自上次CA125检测以来受试者健康状况变化的简短问卷。GCRC将对研究参与者进行抽血，并在每次抽血后24小时内旋转样本。GCRC还将在-70℃下保存样品，直到每周运往中心实验室。

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.