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

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。一个主要