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: 10447573
• 负责人: MICHAEL J MORRIS
• 金额: $ 68.99万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10447573
• 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; 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; Prognosis; 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; predicting response; predictive modeling; prognostic model; progression marker; prospective; radiological imaging; response; serial imaging; soft tissue; temporal measurement; time use; treatment effect; treatment response; tumor; working group; Aftercare; American; Biological Assay; Biological Markers; Bone Tissue; Cancer Etiology; Caring; Cessation of life; Choline; Clinical; Clinical Trials; Data; Data Set; Development; 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; Prognosis; 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; predicting response; predictive modeling; prognostic model; progression marker; prospective; radiological imaging; 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与癌症相关死亡的第二大原因。专业 他们的治疗障碍和为这种疾病开发新药的障碍是缺乏可靠的定量 治疗监测方法。使用循环肿瘤细胞（CTC）的基于流体的肿瘤监测 最近证明对预后和预测治疗反应很有价值。当前的成像方法 前列腺癌中的治疗监测涉及新骨转移或选定指数的病变计数 软组织疾病的病变；两者都专注于进展，无法评估伯恩的全部疾病。 该提案部署了两种经过验证的方法：自动骨扫描指数（ABSI）和淋巴结 分割，以量化标准成像结果，以使伯恩在成像中的总疾病量度 可以在预测模型中与CTC数据集成。该模型将胜过的假设 当前监测治疗反应的方法将通过这些特定目的测试：1）相关 通过成像和CTC评估的肿瘤燃烧的定量后处理变化； 2）确定 基于液体的肿瘤监测（液体活检）和成像测定的结合是否更多 比单独预测生存的任何一种分析要强大； 3）确定液体的最佳组合 用于不同疗法的活检和成像。将建立模型以使用成像预测整体生存， CTC和预后因素数据来自第一线治疗的III期临床试验，多西他赛，多西他赛 + radium-223和abiraterone +泼尼松，用于疾病的晚期阶段，转移性castration- 抗性前列腺癌（MCRPC）。由于 串行成像（CT和骨闪烁显像）和CTC评估的建议作为终点 前列腺癌工作组（PCWG）3指南，由研究团队合作。结果的结果 研究将创建第一个可靠，多参数和完全定量的生物标志物，该标志物在临床上捕获 MCRPC反应和进展的有意义的指标；产生证据以支持其包容性 在将来的PCWG指南中；并开发适用于新成像方式的方法。