Integrated radiomic and liquid biopsy monitoring in SWOG S1802: A phase 3 therapeutic trial for metastatic prostate cancer

SWOG S1802 中的综合放射组学和液体活检监测：转移性前列腺癌的 3 期治疗试验

• 批准号: 10348199
• 负责人: Vinay Duddalwar
• 金额: $ 67.6万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-09 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348199
• 关键词: Abdomen; Address; Biological; Biological Assay; Biology; Biopsy; Biopsy Specimen; Blood; Blood specimen; Cancer Etiology; Cells; Cessation of life; Clinical; Clinical Investigator; Clinical Management; Collaborations; Collection; Data; Data Analyses; Development; Diagnosis; Disease; Disease Progression; Enrollment; Evaluation; Evolution; Genes; Genomics; Goals; Image; Individual; Lead; Letters; Life; Machine Learning; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Metastatic to; Methods; Modality; Modeling; Molecular; Molecular Profiling; Monitor; Multi-Institutional Clinical Trial; Neoplasm Circulating Cells; Newly Diagnosed; Nucleic Acids; Oncology; Outcome; Pathway interactions; Patients; Pelvis; Phase; Phenotype; Plasma; Plasma Cells; Population; Primary Neoplasm; Progression-Free Survivals; Prospective cohort; Protocols documentation; RNA; Radiation Oncology; Randomized; Research Personnel; Resistance; Retrieval; Sampling; Scanning; Screening for Prostate Cancer; Site; Synaptophysin; Systemic Therapy; Techniques; Testing; Therapeutic Trials; Time; Tissues; Work; X-Ray Computed Tomography; advanced disease; base; cohort; cost; cost effective; genomic biomarker; high throughput analysis; image processing; imaging biomarker; improved; insight; liquid biopsy; men; minimally invasive; multidisciplinary; novel; novel therapeutics; peripheral blood; phase III trial; phenomics; predicting response; predictive modeling; predictive signature; predictive tools; prognostic signature; prognostic tool; prospective; radiological imaging; radiomics; response; sample collection; survival prediction; targeted sequencing; therapy resistant; tool; treatment optimization; tumor

Abstract Prostate cancer (PC) afflicts more men in the U.S. than any other malignancy and is the second leading cause of cancer death in this population. Recently, new therapies have improved survival in some men but have offered little benefit to others. Tissue profiling has identified genes and pathways associated with resistance and progression to advanced disease, but little is known about the dynamics of when and how such changes arise during therapy. Such insights can only be gained through minimally invasive monitoring that allows repeated disease profiling over time. Our multidisciplinary team has developed and tested two such minimally invasive monitoring capabilities: The first is multi-parametric liquid biopsy: streamlined analysis of blood samples that simultaneously measures PC-relevant cellular and molecular features from single circulating tumor cells and matched plasma cell-free nucleic acids. The second is radiomic analysis: high-throughput extraction of quantitative metrics to identify PC-relevant phenomic imaging features. By synergizing the strengths of the two methods, our goal is to test the hypothesis that liquid biopsy and radiomic techniques can be applied jointly to monitor metastatic PC noninvasively over time, culminating in new prognostic and predictive tools to guide therapy. To maximize the impact of our findings, liquid biopsy profiling and radiomic analysis will be integrated into Southwest Oncology (SWOG) S1802, a phase 3 prospective therapeutic trial for over 1200 men with newly diagnosed metastatic castrate sensitive prostate cancer (mCSPC) treated with standard systemic therapy alone or in combination with definitive treatment of the primary tumor. Notably, SWOG and the other participating cooperative groups have reviewed and approved this proposal (see Letters of Support), and the requisite blood samples and CT scans already are being collected as part of the active protocol. In this unique setting, we will pursue three Specific Aims. We will: 1. Use multi-parametric liquid biopsies to monitor the evolving cellular and molecular landscape of mCSPC during treatment in S1802; 2. Use radiomic analysis of CT scans to monitor the evolving radiographic landscape of mCSPC during treatment in S1802; and 3. Integrate cellular, molecular, and radiomic data to develop composite disease monitoring models predictive of PFS and OS. Importantly, liquid biopsies and CT images will be matched within patients and analyzed at key inflection points over the course of the trial: at diagnosis, after initiation of systemic therapy, after definitive therapy, and at disease progression. In this way, the proposed work will illuminate when and how PC-relevant phenotypes arise during therapy, and how they relate to clinical outcomes. In particular, we will better understand which components of the liquid biopsy – circulating cells, plasma, or both – most accurately reflect the tumor's evolving molecular profile, which radiomic metrics most closely correlate with these molecular features and can serve as early cost-effective indicators of emerging resistance, and which composite models combining liquid biopsy and radiomic features best predict PFS and OS and can serve as powerful minimally-invasive tools to monitor and adjust therapy.

摘要 在美国，前列腺癌(PC)是困扰男性人数最多的恶性肿瘤，是第二大致病原因 在这一人群中癌症死亡的风险。最近，新的疗法提高了一些男性的存活率，但也提供了 对其他人几乎没有好处。组织图谱已经确定了与耐药性相关的基因和途径 进展为晚期疾病，但对这种变化何时以及如何发生的动力学知之甚少 在治疗期间。这种洞察只能通过允许重复进行的微创监测来获得 随着时间的推移疾病概况。我们的多学科团队已经开发并测试了两种这样的微创 监测能力：第一种是多参数液体活检：简化的血样分析， 同时检测单个循环肿瘤细胞的PC相关细胞和分子特征 匹配的不含浆细胞的核酸。第二种是放射学分析：高通量提取 用于识别与PC相关的表观成像特征的定量指标。通过将两者的优势协同起来 方法，我们的目标是验证液体活检和放射组学技术可以联合应用于 随着时间的推移非侵入性地监测转移性PC，最终形成新的预测和预测工具来指导 心理治疗。为了最大限度地发挥我们发现的影响，液体活组织检查和放射学分析将整合在一起。 进入西南肿瘤(SWOG)S1802，这是一项针对1200多名患有新发癌症的男性的3期前瞻性治疗试验 确诊的转移性去势敏感型前列腺癌(MCSPC)单独接受标准系统治疗 或结合对原发肿瘤的明确治疗。值得注意的是，SWOG和其他参与者 合作团体已经审查和批准了这项提议(见支持信)，并提供了必要的血液 样本和CT扫描已经作为活动方案的一部分进行了收集。在这个独特的环境中，我们将 追求三个具体目标。我们将：1.使用多参数液体活检来监测进化中的细胞和 MCSPC在S1802治疗过程中的分子图谱；2.利用CT扫描的放射组学分析来监测 在S1802治疗过程中MCSPC的放射学图像演变；以及3.整合细胞、分子和 放射学数据，以开发预测PFS和OS的复合疾病监测模型。重要的是，液体 活检和CT图像将在患者体内进行匹配，并在关键转折点进行分析 试验：在诊断时、系统治疗开始后、确定治疗后和疾病进展时。在……里面 通过这种方式，拟议的工作将阐明PC相关表型在治疗过程中何时以及如何出现，以及如何出现 它们与临床结果有关。特别是，我们将更好地了解液体活组织检查的哪些组成部分- 循环细胞，血浆，或两者兼而有之--最准确地反映了肿瘤分子的演变，这是放射学的 指标与这些分子特征最密切相关，可以作为早期经济有效的指标 新出现的耐药性，以及哪种结合液体活检和放射学特征的组合模型最能预测 PFS和OS，可以作为强大的微创工具来监测和调整治疗。