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：细胞减少手术和联合化疗的进展提高了5年生存率 在上皮卵巢癌的患者中 几十年。计算机模型表明，在早期发现卵巢癌（I-II）可以提高卵巢癌 治愈10-30％。在两个主要试验中，这是一个两阶段策略，其中CA125的上升值用贝叶斯分析 卵巢癌算法（ROCA）的风险促使经阴道超声和异常成像引发 手术提供了足够特异性的超过10％的阳性预测值（PPV）。在EDRN的支持下， 7,869名显然健康的女性参加了正常风险卵巢癌筛查研究 （NROSS）在美国的11个不同地点，在过去21年中，确定了46,008个CA125。 已转介有29名患者，用于在早期发现17例卵巢癌的手术。 我或II。此外，检测到4例早期子宫内膜癌病例，产生了用于检测癌症的PPV 72％。检测每例卵巢癌的操作将不超过2-3个手术。如CA125 仅由80％的上皮卵巢癌表达，可以通过多个来实现更好的敏感性 生物标志物。在此赠款周期中，我们报告说HE4，HE4抗原 - 自动抗体复合物和 骨桥蛋白显着提高了CA125对早期阶段（I-II）疾病的敏感性，并具有 开发了一个ROCA2，其中包括所有4种生物标志物，并比早期疾病早于1.4至4。8年 罗卡。我们发现20-25％的卵巢抗TP53自身抗体（AA）升高 癌症。抗TP53的滴度在CA125前12个月和诊断前22个月升高 CA125不会增加。在EDRN联盟中，来自弗雷德·哈钦森癌症中心的研究人员 亚利桑那州立大学和马萨诸塞州综合医院，我们比较了5个抗TP53自动抗体 测定并发现快速测定最敏感。标准已分配了大约28个不同的AA 952种血清的面板可识别三个-TP53，CTAG1和IL -8 - 可以在早期疾病和 补体CA125。在过去的二十年中，我们收集并保存了922血和774张组织 卵巢癌患者初次手术时的样品。在过去的6。5年中，我们已经养了 来自NROSS的18,754种新的血清和血浆样品，并为11 研究人员测试生物标志物的早期卵巢癌。我们已经发表了23篇同行评审的文章， 评论和评论。由36名调查人员和员工组成的团队将追求3个具体目标：1） NROSS2试验确定使用4 生物标志物roca2和3个自动抗体的面板； 2）评估多个生物标志物以早期检测 在积极的次观察行动中，疾病的复发或持久性； 3）维护和分享系列 和等离子体库，以促进对新型生物标志物进行早期检测的评估。