Molecular Characterization Trial

项目摘要 分子表征试验（MCT）是ROBIN的生物标本和数据资源的来源 中心因此，它的成功对整个倡议的成功至关重要， 这些基本资源的获得将加快这些资源的使用时间， 在研究项目和核心中进行的所有创新工作。哈佛/加州大学旧金山分校罗宾选择了 对于其主题，儿科恶性肿瘤研究是深入调查其影响的最佳环境。 异质性，在其肿瘤细胞的内在和外在表现，对辐射反应。的mct 将通过以下目标实现这些目标：目标1：协调生物标本的收集， ROBIN研究中使用的合作组研究的临床数据。MCT将利用两个正在进行的 试验：太平洋儿科神经肿瘤联盟PNOC 023用于弥漫性中线胶质瘤（DMG），以及 儿童肿瘤组（COG）ANBL 1531用于神经母细胞瘤（NBL）。每项试验的研究椅都是共同的， 分别是MCT和项目2的负责人。作为MCT的一个新特征，匹配的肿瘤样本对 将从接受治疗前活检并随后接受治疗后活检的受试者中获得 手术（NBL）或死后（DMG）组织。罗宾调查员将 此外，他们还可以利用其他资源，包括30个DMG 与PNOC 023研究中获得的肿瘤样本不同且已在手中。MCT将 还通过从COG晚期效应中获得血液样本和临床数据来支持晚期效应的目标， 高风险神经母细胞瘤（LEAHRN）研究，其中包括24名长期生存者，以前接受过 放射性药物131I-MIBG。目标2：管理MCT的监管方面，包括研究中心方案 用于在机构生物储存库中收集受保护的健康信息（PHI）和生物标本。临床 研究和数据协调员将与Dana-Farber/哈佛癌症中心和 UCSF确保严格和及时提交研究方案，修正案和持续审查， 这项工作可以稳步进行。此外，由于所有的PHI将流经MCT，这提供了去- 识别的资源提供给其他ROBIN组件，这将最大限度地降低受试者保密风险。目标3： 维护处理和分析肿瘤、血液和CSF样本的标准操作规程， 存储输入和结果的高维数据。由于涉及大量数据， 进行复杂的分析，必须以协调的方式进行工作，以保持 严谨性和可重复性。MCT将依靠临床人工智能内的综合专业知识 和成像核心以及分子数据科学和高级剂量学核心，以确保合规性 与去识别和数据存储标准，使丰富的资源产生的ROBIN可以 被更广泛的研究界有效地用于试点项目和其他项目。

PROJECT SUMMARY The Molecular Characterization Trial (MCT) is the source of biospecimen and data resources for the ROBIN Center. As such, its success is paramount to the success of the entire initiative, and strategies that expedite the acquisition of these essential resources will accelerate the timeframe in which they are made available for all the innovative work performed in the Research Projects and Cores. The Harvard/UCSF ROBIN has chosen for its theme the study of pediatric malignancies as the optimal setting for in depth investigation into the impact of heterogeneity, in both its tumor cell intrinsic and extrinsic manifestations, on radiation responses. The MCT will achieve these goals via the following Aims: Aim 1: Coordinate the collection of biospecimens and clinical data from cooperative group studies for use in ROBIN studies. The MCT will leverage two ongoing trials: Pacific Pediatric Neuro-Oncology Consortium PNOC023 for diffuse midline glioma (DMG), and Children’s Oncology Group (COG) ANBL1531 for neuroblastoma (NBL). The study chairs for each trial are co- leads of the MCT and Project 2, respectively. As a novel feature of the MCT, matched pairs of tumor samples will be available from subjects who underwent pre-treatment biopsies and subsequently had post-treatment surgical (NBL) or post-mortem (DMG) tissues obtained via established protocols. The ROBIN investigators will also leverage additional resources that are uniquely available to them, including a collection of thirty DMG tumor samples that are distinct from those obtained on the PNOC023 study and already in hand. The MCT will also bolster an aim on late effects by obtaining blood samples and clinical data from the COG Late Effects after High-Risk Neuroblastoma (LEAHRN) study, which includes 24 long-term survivors previously treated with the radiopharmaceutical 131I-MIBG. Aim 2: Manage the regulatory aspects of the MCT, including site protocols for collection of protected health information (PHI) and biospecimens in institutional biorepositories. Clinical research and data coordinators will work with site leads at both Dana-Farber/Harvard Cancer Center and UCSF to ensure rigorous and timely submission of study protocols, amendments, and continuing reviews so that the work can steadfastly proceed. Also, because all PHI will flow through the MCT, which provides de- identified resources to other ROBIN components, this will minimize risks to subject confidentiality. Aim 3: Maintain standard operating procedures for processing and analyzing tumor, blood and CSF samples and storing incoming and resultant high-dimensional data. Given the vast amounts of data involved, and the intricate assays being performed, it is essential that the work is performed in a harmonized way to maintain rigor and reproducibility. The MCT will rely on the combined expertise within the Clinical Artificial Intelligence and Imaging Core and the Molecular Data Science and Advanced Dosimetry Core to ensure compliance with de-identification and data storage standards so that the rich resources generated by the ROBIN can be used effectively by the broader research community in pilot projects and beyond.