Clinical Qualification of Imaging and Fluid-Based Tumor Monitoring Biomarkers for Metastatic Castration Resistant Prostate Cancer

转移性去势抵抗性前列腺癌的影像学和基于液体的肿瘤监测生物标志物的临床资格

• 批准号: 9974088
• 负责人: MICHAEL J MORRIS
• 金额: $ 71.97万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9974088
• 关键词: Aftercare; American; Biological Assay; Biological Markers; Bone Tissue; Cancer Etiology; Caring; Cessation of life; Choline; Clinical; Clinical Trials; Data; Data Set; Development; Diagnostic radiologic examination; Disease; Event; FOLH1 gene; Future; Goals; Guidelines; Image; Imaging Techniques; Lesion; Liquid substance; Lymph; Malignant neoplasm of prostate; Measurement; Measures; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Methods; Modality; Modeling; Molecular; Monitor; Neoplasm Circulating Cells; Outcome; Patients; Performance; Phase III Clinical Trials; Positron-Emission Tomography; Prednisone; Prognostic Factor; Progression-Free Survivals; Radiation therapy; Radionuclide Imaging; Radium; Recommendation; Research; Research Design; Soft Tissue Disorder; Standardization; Statistical Models; Techniques; Testing; Time; Training; Tumor Burden; Validation; abiraterone; base; bone; bone imaging; burden of illness; castration resistant prostate cancer; chemotherapy; clinical care; docetaxel; drug development; image processing; imaging biomarker; imaging modality; improved; indexing; kinetic model; liquid biopsy; lymph nodes; men; novel; novel imaging technique; novel therapeutics; outcome forecast; predicting response; predictive modeling; progression marker; prospective; response; serial imaging; soft tissue; temporal measurement; time use; treatment effect; treatment response; tumor; working group

Metastatic prostate cancer is the second largest cause of cancer-related death in American men. A major obstacle to their treatment and to developing new drugs for this disease is the lack of reliable quantitative treatment monitoring methods. Fluid-based tumor monitoring using circulating tumor cells (CTC) has recently proven valuable for prognosis and predicting response to treatment. Current imaging methods for treatment monitoring in prostate cancer involve lesion-counting of new bone metastases or selected index lesions of soft tissue disease; both focus on progression only and cannot assess the full disease burden. This proposal deploys two validated methods, automated bone scan index (aBSI) and lymph node segmentation, to quantify standard imaging results so that a measure of total disease burden on imaging can be integrated with CTC data in a predictive model. The hypothesis that this model will outperform current methods for monitoring response to therapy will be tested via these specific aims: 1) Correlate quantitative post-treatment changes in tumor burden as assessed by imaging and CTC’s; 2) Determine whether a combination of fluid-based tumor monitoring (liquid biopsy) and an imaging assay is more powerful than either assay alone in prognosticating for survival; 3) Identify the optimal combination of liquid biopsy and imaging for different therapies. Models will be built to predict overall survival using imaging, CTC, and prognostic factor data from phase III clinical trials of first-line treatments, docetaxel, docetaxel + radium-223, and abiraterone + prednisone, for an advanced stage of disease, metastatic castration- resistant prostate cancer (mCRPC). Clinical trials including this data are available for analysis due to the recommendations for serial imaging (CT and bone scintigraphy) and CTC assessment as endpoints in the Prostate Cancer Working Group (PCWG) 3 guidelines, co-authored by the study team. The results of this study will create the first reliable, multiparametric, and fully quantitative biomarker that captures clinically meaningful indices of both response and progression in mCRPC; generate evidence to support its inclusion in future PCWG guidelines; and develop methods applicable to new imaging modalities.

转移性前列腺癌是美国男性癌症相关死亡的第二大原因。一位少校 他们治疗和开发治疗这种疾病的新药的障碍是缺乏可靠的定量 治疗监测方法。利用循环肿瘤细胞(CTC)进行基于液体的肿瘤监测 最近被证明对预后和预测治疗反应有价值。当前的成像方法 前列腺癌的治疗监测包括对新骨转移的病变计数或选定的指标 软组织疾病的损害；两者都只关注进展，不能评估全部疾病负担。 这项建议部署了两种经过验证的方法，自动骨扫描指数(ABSI)和淋巴结节 分割，以量化标准的成像结果，以便对成像上的总疾病负担进行衡量 可以在预测模型中与CTC数据集成。假设这一模型的表现会更好 目前监测治疗反应的方法将通过以下具体目标进行测试：1)相互关联 通过成像和CTC评估治疗后肿瘤负荷的定量变化；2)确定 基于液体的肿瘤监测(液体活组织检查)和成像分析的组合是否比 在预测生存方面比任何一种检测方法都更有效；3)确定液体的最佳组合 不同治疗方法的活组织检查和成像。将建立模型来使用成像来预测总体存活率， CTC，以及来自第一线治疗的III期临床试验的预后因素数据，多西紫杉醇，多西紫杉醇+ 镭-223，阿比特龙+泼尼松，用于晚期疾病，转移性去势- 耐药前列腺癌(MCRPC)。包括这一数据的临床试验可供分析，因为 系列成像(CT和骨显像)和CTC评估作为临床检查终点的建议 前列腺癌工作组(PCWG)3指南，由研究团队共同撰写。这样做的结果 这项研究将创造第一个可靠的、多参数的、完全定量的生物标志物，它可以在临床上捕捉到 MCRPC反应和进展的有意义的指数；产生证据支持其纳入 在未来的盈科工作组指南中；并开发适用于新的成像模式的方法。