MD Anderson Cancer Center EDRN- Clinical Validation Center for Early Detection of Ovarian Cancer with a multiple marker algorithm

MD 安德森癌症中心 EDRN - 使用多标记算法早期检测卵巢癌的临床验证中心

• 批准号: 10700583
• 负责人: ROBERT C BAST
• 金额: $ 101.43万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-05 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700583
• 关键词: Algorithms; Antigens; Arizona; Autoantibodies; Benign; Biological Assay; Biological Markers; Blood; Blood Tests; CA-125 Antigen; CTAG1 gene; Cancer Center; Cancer Detection; Clinical; Collaborations; Combination Drug Therapy; Complement; Complex; Computer Models; Diagnosis; Disease; Early Detection Research Network; Early Diagnosis; Endometrial Carcinoma; Epithelial ovarian cancer; Evaluation; FOLR1 gene; General Hospitals; Goals; Grant; IL8 gene; Image; Individual; Lead; Lesion; Link; Malignant neoplasm of ovary; Massachusetts; Measurement; Measures; Operative Surgical Procedures; Ovarian; Ovary; Patients; Peer Review; Pelvis; Plasma; Postmenopause; Predictive Value; Published Comment; Publishing; Recurrence; Recurrent Malignant Neoplasm; Recurrent disease; Reporting; Research Personnel; Risk; Sampling; Screening for Ovarian Cancer; Second Look Surgery; Serum; Site; Specificity; Specimen; TP53 gene; Technology; Testing; Time; Tissue Sample; Tissues; Tumor Debulking; Ultrasonography; United Kingdom; United States; Universities; Vagina; Validation; WFDC2 gene; Woman; advanced disease; biomarker identification; cancer recurrence; chemotherapy; collaborative trial; disease heterogeneity; early detection biomarkers; improved; mortality; novel marker; operation; osteopontin; preservation; rapid test; routine screening; screening; ultrasound

ABSTRACT: Advances in cytoreductive surgery and combination chemotherapy have improved 5-year survival in patients with epithelial ovarian cancer, but the rate of cure remains essentially unchanged over the last two decades. Computer models suggest that detection of ovarian cancer in early stage (I-II) could improve rates of cure by 10-30%. In two major trials, a two-stage strategy where rising values of CA125 analyzed with a Bayesian Risk of Ovarian Cancer Algorithm (ROCA) prompted transvaginal sonography and abnormal imaging prompted surgery proved sufficiently specific to exceed a positive predictive value (PPV) of 10%. With support of the EDRN, 7,869 apparently healthy women have participated in the Normal Risk Ovarian Cancer Screening Study (NROSS) at 11 different sites in the United States with 46,008 CA125 determinations over the last 21 years. Twenty-nine patients have been referred for operations detecting 17 ovarian cancers with 12 (71%) in early stage I or II. In addition, 4 cases of early stage endometrial cancer were detected, yielding a PPV for detecting cancer of 72%. No more than 2-3 operations will be required to detect each case of ovarian cancer. As CA125 is expressed by only 80% of epithelial ovarian cancers, better sensitivity is likely to be achieved with multiple biomarkers. During this grant cycle we have reported that HE4, HE4 antigen-autoantibody complexes, and osteopontin significantly enhance the sensitivity of CA125 for detecting early stage (I-II) disease and have developed a ROCA2 that includes all 4 biomarkers and detects advanced disease 1.4 to 4.8 years earlier than ROCA. We have found elevated levels of anti-TP53 autoantibodies (AA) in 20-25% of patients with ovarian cancer. Titers of anti-TP53 rise 12 months prior to CA125 and 22 months prior to diagnosis in patients where CA125 does not increase. In an EDRN consortium with investigators from Fred Hutchinson Cancer Center, Arizona State University and the Massachusetts General Hospital, we have compared 5 anti-TP53 autoantibody assays and found the RAPID assay most sensitive. Some 28 different AA have been assayed in a standard panel of 952 sera to identify three - TP53, CTAG1, and IL-8 – that can be detected in early stage disease and complement CA125. Over the last two decades, we have collected and preserved 922 blood and 774 tissue samples at the time of initial surgery in patients with ovarian cancers. During the last 6.5 years we have banked 18,754 new serum and plasma samples from the NROSS and provided serum/plasma samples for 11 investigators to test biomarkers for early stage ovarian cancer. We have published 23 peer reviewed articles, reviews and commentaries. A team of 36 investigators and staff will pursue 3 Specific Aims: 1) to conduct the NROSS2 trial to determine the specificity and PPV of a two-stage ovarian cancer screening strategy using a 4 biomarker ROCA2 and a panel of 3 autoantibodies; 2) to evaluate multiple biomarkers for early detection of recurrence or persistence of disease at positive second look operations; and 3) to maintain and share a serum and plasma bank to facilitate evaluation of novel biomarkers for early detection of ovarian cancer.

摘要：肿瘤细胞减灭术和联合化疗的进步提高了 5 年生存率 上皮性卵巢癌患者的治愈率在过去两年中基本保持不变 几十年来，计算机模型表明，早期（I-II）卵巢癌的检测可以提高卵巢癌的发病率。 在两项主要试验中，采用贝叶斯分析 CA125 值上升的两阶段策略。 卵巢癌风险算法（ROCA）提示经阴道超声检查和异常影像提示 在 EDRN 的支持下，手术被证明具有足够的特异性，超过了 10% 的阳性预测值 (PPV)。 7,869 名表面健康的女性参加了正常风险卵巢癌筛查研究 (NROSS) 在美国 11 个不同地点在过去 21 年中进行了 46,008 次 CA125 测定。 29 名患者已转诊接受手术，检测出 17 种卵巢癌，其中 12 例 (71%) 处于早期阶段 此外，还检测到 4 例早期子宫内膜癌，产生用于检测癌症的 PPV。 72%，检测每例卵巢癌不需要超过 2-3 次手术。 仅 80% 的上皮性卵巢癌表达，通过多种方法可能会获得更好的敏感性 在此资助周期中，我们报告了 HE4、HE4 抗原-自身抗体复合物和 骨桥蛋白显着增强 CA125 检测早期 (I-II) 疾病的敏感性，并具有 开发了一种包含所有 4 种生物标志物的 ROCA2，可以比之前提前 1.4 至 4.8 年检测晚期疾病 ROCA。我们发现 20-25% 的卵巢癌患者体内抗 TP53 自身抗体 (AA) 水平升高。 癌症患者的抗 TP53 滴度在 CA125 之前 12 个月和诊断前 22 个月上升。 在与 Fred Hutchinson 癌症中心的研究人员组成的 EDRN 联盟中，CA125 没有增加。 亚利桑那州立大学和麻省总医院，我们比较了5种抗TP53自身抗体 并发现 RAPID 最灵敏的测定已在标准中测定了约 28 种不同的 AA。 952 份血清组可识别 TP53、CTAG1 和 IL-8 三种，可在早期疾病和 CA125。在过去的二十年里，我们收集并保存了 922 份血液和 774 份组织补体。 在过去 6.5 年里，我们储存了卵巢癌患者初次手术时的样本。 NROSS 提供了 18,754 份新的血清和血浆样本，并为 11 名患者提供了血清/血浆样本 研究人员测试早期卵巢癌的生物标志物，我们发表了 23 篇同行评审文章， 由 36 名研究人员和工作人员组成的团队将追求 3 个具体目标：1) 进行审查和评论。 NROSS2 试验使用 4 种方法确定两阶段卵巢癌筛查策略的特异性和 PPV 生物标志物 ROCA2 和一组 3 种自身抗体；2) 评估多种生物标志物以进行早期检测 在二次检查呈阳性的手术中疾病复发或持续存在；以及 3) 维持和共享血清 和血浆库，以促进评估用于早期检测卵巢癌的新型生物标志物。