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

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 他们的治疗和开发这种疾病的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）的基于液体的肿瘤监测具有 最近被证明对预后和预测治疗反应有价值。目前的成像方法 前列腺癌的治疗监测包括新骨转移病灶计数或选定指标 软组织疾病的病变;两者都只关注进展，不能评估全部疾病负担。 该提案部署了两种有效的方法，自动骨扫描指数（aBSI）和淋巴结 分割，以量化标准成像结果，以便测量成像上的总疾病负担 可以与CTC数据集成在预测模型中。假设这个模型将优于 目前用于监测对治疗的反应的方法将通过这些特定目的进行测试：1）相关 通过成像和CTC评估的肿瘤负荷的定量治疗后变化; 2）确定 基于液体的肿瘤监测（液体活检）和成像测定的组合是否更 比单独的任一种测定法更有力地证实存活; 3）鉴定液体的最佳组合， 活检和成像用于不同的治疗。将建立模型，使用成像预测总生存率， 一线治疗、多西他赛、多西他赛+多西他赛的III期临床试验的CTC和预后因素数据 镭-223和阿比特龙+泼尼松，用于晚期疾病，转移性去势- 耐药前列腺癌（mCRPC）。包括该数据的临床试验可用于分析，因为 建议将系列成像（CT和骨密度成像）和CTC评估作为终点， 前列腺癌工作组（PCWG）3指南，由研究小组共同撰写。的结果 这项研究将创建第一个可靠的、多参数的、完全定量的生物标志物， mCRPC中有意义的缓解和进展指标;生成支持纳入的证据 在未来的PCWG指南中;并制定适用于新成像模式的方法。

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.