Molecular Characterization Trial

项目总结 分子表征试验 导航用于治疗选择的扩展样本调查(Robin-NESSTS) 摘要：大约一半的癌症患者在病程中接受了放射治疗。 在辐射优化中应用新的生物学知识是一个机会和迫切需要 治疗及其与新兴靶向抗肿瘤药物的联合。在CCF/埃默里的核心 Robin U54中心是一项分支分子表征试验(MCT)，专注于纵向收集 来自肌肉浸润性膀胱癌(MIBC)和头颈部肿瘤患者的生物光谱和多模式数据 颈部鳞状细胞癌(HNSCC)在放疗前、放疗中和放疗后。这些分子 特征队列也被设计成包括免疫调节联合疗法 作为标准护理放化疗，旨在通过将 这些试验贯穿了罗宾中心的核心和项目。这些都是以免疫放射生物学为中心的 “小N，高含量”的研究队列，这将使我们能够解决与 综合方式放射治疗的生物学基础反应。正在测试的中心假设是 从之前治疗的患者的临床注释的生物显微镜和多模式数据的纵向收集， 在放射治疗期间和之后，由MCT队列检查基于辐射的免疫疗法和标准 CARE化学放射治疗将提供新的见解，以了解癌症的遗传、免疫学和进化基础 治疗反应。询问两种不同癌症的关键问题的能力将放大我们的 识别辐射抗性和可概括的分子机制的能力 免疫调节活性。我们的具体目标是进行标本收集和表征试验 有2个队列：(1)(MCTA)：自适应放射治疗联合Sacituzumab Govitecan(RAD-SG)，用于 MIBC患者的膀胱保留和(2)调强放疗再照射加同期和 佐剂尼伏卢单抗。相同的样本和数据采集将从两个平行的队列中获得 标准护理顺铂加RT治疗的患者(每个部位20例)。最高法院的首要目标是- 本MCT的内容研究队列是严格剖析疗效的共同机制和驱动因素 对两种癌症中最有希望的基于辐射的组合的抵抗力。我们将解决知识问题 与免疫调节反应的遗传、免疫学和分子进化基础相关的差距 通过无缝集成来自这些临床队列的多模式数据 罗宾中心的实验室、项目和核心。

PROJECT SUMMARY Molecular Characterization Trial Navigating Extended Specimen Surveys for Therapeutic Selection (ROBIN-NESSTS) Summary: Approximately half of all cancer patients are treated with radiation in the course of their disease. There exists an opportunity and urgent need to apply new biological knowledge in the optimization of radiation treatment and its combination with emerging targeted anti-neoplastic agents. At the core of the CCF/Emory ROBIN U54 Center is a branched Molecular Characterization Trial (MCT) focused on longitudinal collection of biospecimens and multimodal data from patients with muscle invasive bladder cancer (MIBC) and head and neck squamous cell carcinoma (HNSCC) prior to-, during, and after radiotherapy. These molecular characterization cohorts have been designed to incorporate immunomodulatory combination therapies as well as standard-of-care chemoradiotherapy, aiming to address pressing translational questions by integrating these trials throughout the ROBIN Center’s cores and projects. These are immune radiobiology-centered “small N, high-content” study cohorts that will allow us to address critical knowledge gaps related to the biological basis responses to combined modality radiotherapy. The central hypothesis being tested is that the longitudinal collection of clinically annotated biospecimens and multimodal data from patients treated prior to, during, and after radiotherapy from MCT cohorts examining radiation-based immunotherapies and standard of care chemoradiation will provide new insights into the genetic, immunologic, and evolutionary basis of therapeutic response. The ability to interrogate key questions across two distinct cancers will amplify our capacity to identify generalizable molecular mechanisms underlying radiation resistance and immunomodulatory activity. Our Specific Aims are to conduct a specimen collection and characterization trial with 2 cohorts: (1) (MCTa): Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (RAD-SG) for bladder preservation in patients with MIBC and (2) a Phase II trial of IMRT re-irradiation plus concurrent and adjuvant nivolumab. The same sample and data acquisition will be obtained from two parallel cohorts of standard of care cisplatin plus RT treated patients (n=20 for each site). The overarching objective of the high- content study cohorts in this MCT is to rigorously dissect common mechanisms and drivers of efficacy and resistance to the most promising radiation-based combinations in two cancers. We will address knowledge gaps related to the genetic, immunologic, and molecular evolutionary basis of response to immunomodulatory combination therapies by seamlessly integrating multi-modal data from these clinical cohorts across the ROBIN Center’s laboratories, projects, and cores.