METEOR-Comprehensive Radiobiology Assessment TRial (METEOR-CRATR)

METEOR-综合放射生物学评估试验 (METEOR-CRATR)

• 批准号: 10715021
• 负责人: Clifford Grant Robinson
• 金额: $ 6.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715021
• 关键词: Adjuvant Chemotherapy; Basic Science; Biopsy; Cells; Cisplatin; Clinical; Clinical Data; Collaborations; Collection; Combined Modality Therapy; Complex; Coupled; Cytotoxic Chemotherapy; Data; Data Collection; Dendritic Cells; Development; Disease; Disease Outcome; Dose; Excision; External Beam Radiation Therapy; Failure; Foundations; Fractionation; Future; Generations; High-Dose Rate Brachytherapy; Image; Immune system; Immunotherapy; Infrastructure; Localized Disease; Locally Advanced Malignant Neoplasm; Macrophage; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of pancreas; Modality; Modeling; Molecular; Neoadjuvant Therapy; Operative Surgical Procedures; Outcome; Paint; Patients; Pelvis; Pilot Projects; Prognosis; Radiation; Radiation Dose Unit; Radiation therapy; Radiobiology; Recurrence; Recurrent disease; Registries; Relapse; Research Project Grants; Resistance; Resource Sharing; Resources; Risk; Role; Sampling; Solid Neoplasm; Specimen; Structure; System; T-Lymphocyte; Testing; Time; Tumor Immunity; Tumor Promotion; Universities; Washington; advanced pancreatic cancer; biomarker identification; chemoradiation; chemotherapy; cohort; curative treatments; design; early phase trial; image guided; improved; improved outcome; irradiation; multimodality; patient population; prospective; radiation effect; radiation resistance; response; standard of care; success; therapy development; therapy resistant; trial design; tumor; tumor microenvironment

MOLECULAR CHARACTERIZATION TRIAL SUMMARY The standard of care (SOC) for locally advanced cervical cancer, pelvic radiation (RT) with concurrent cisplatin, is associated with a 30-50% failure rate, and there is no cure for recurrent disease. Our preliminary data suggests that a complex interaction between macrophages, dendritic cells, and T-cells within the tumor microenvironment (TME), as remodeled by radiotherapy, may limit the development of anti-tumor immunity and promote development of treatment resistance in these tumor types. The Washington University (WU) ROBIN Center (MicroEnvironment Tumor Effects Of Radiotherapy (METEOR)), will create a resource for in tandem single cell and spatially resolved omics that will be used to study how the immune system co-evolves with tumors during RT, which will be combined with well-annotated clinical, dosimetric, and imaging data to paint a detailed picture of RT/TME interactions. Specifically, we will study how standard of care chemotherapy, radiation and combined chemoradiation remodels TME, and how this contributes to tumor relapse and the development of radiation resistance. A molecular characterization trial (Comprehensive Radiobiology Assessment TRial (METEOR-CRATR)) will be initiated to support detailed studies in this space within the context of our two METEOR Center Projects and lay a foundation for future studies (trans-ROBIN pilot studies, additional inter/intra- Network collaboration, future P01/R01). We hypothesize that a dynamically adaptable Trial design focused on deep characterization of small patient cohorts, coupled with a robust infrastructure to enable rapid provision of samples for analysis, will enable generation of new radiobiological concepts related to changes in the TME in response to standard of care radiotherapy. We will prospectively evaluate changes in the TME through collection of longitudinal biospecimen and multimodal clinical data for patients with locally advanced cervical and pancreatic cancer undergoing standard of care chemoradiotherapy. To allow for optimal collection of data to support comparisons within and across groups, METEOR-CRATR will be initiated in patient populations where the standard of care therapy includes radiotherapy and cytotoxic chemotherapy, and where various opportunities for acquisition of both biopsy and surgical samples during a patient's treatment course naturally exists. We will also enable a robust iterative infrastructure to support rapid provision of samples and clinical data to enable near real-time processing and analysis within the Center Shared Resource Cores (SRCs) and Research Projects. We have developed a responsive system between METEOR-CRATR, SRCs, and Research Projects to enable efficient specimen and data capture and analysis. Such a system will also support dynamic Trial iteration and refinement based on new data and evolving challenges.

分子表征试验总结 局部晚期宫颈癌的标准治疗（SOC），盆腔放疗（RT）联合顺铂， 与30-50%的失败率相关，并且没有治愈复发性疾病的方法。我们的初步数据显示 肿瘤微环境中巨噬细胞、树突状细胞和T细胞之间的复杂相互作用 (TME)放射治疗后，肿瘤细胞的形态发生了改变，这可能限制了抗肿瘤免疫的发展， 在这些肿瘤类型中产生治疗抗性。华盛顿大学（WU）罗宾中心 （放射治疗的微环境肿瘤效应（METEOR）），将为串联单细胞 和空间分辨组学，将用于研究免疫系统如何与肿瘤共同进化， RT，它将与注释良好的临床，剂量测定和成像数据相结合，以描绘详细的画面 RT/TME相互作用。具体来说，我们将研究如何标准护理化疗，放疗和联合治疗。 放化疗重塑TME，以及这如何有助于肿瘤复发和放疗的发展 阻力分子表征试验（综合放射生物学评估TRial （METEOR-CRATR））将启动，以支持在我们的两个背景下在这一领域的详细研究 METEOR中心项目，并为未来的研究奠定基础（跨ROBIN试点研究，额外的跨/内 网络协作，未来的P01/R 01）。我们假设，动态适应性试验设计的重点是 小患者队列的深入表征，再加上强大的基础设施，能够快速提供 用于分析的样品，将能够产生与TME变化有关的新的放射生物学概念， 对标准治疗放疗的反应。我们将前瞻性地评估TME的变化， 局部晚期宫颈癌患者的纵向生物标本和多模式临床数据， 接受标准化放疗的胰腺癌。为了实现数据的最佳收集， 支持组内和组间比较，METEOR-CRATR将在患者人群中启动， 护理治疗的标准包括放射疗法和细胞毒性化学疗法， 用于在患者的治疗过程期间采集活组织检查和手术样本两者的装置自然存在。我们将 还支持强大的迭代基础设施，以支持快速提供样本和临床数据， 中心共享资源核心（SRC）和研究项目内的实时处理和分析。我们 在METEOR-CRATR、SRC和研究项目之间开发了一个响应系统， 高效的样本和数据采集与分析。这样的系统还将支持动态试验迭代， 根据新数据和不断变化的挑战进行改进。