Radiation Oncology at the Interface of Pediatric Cancer Biology and Data Science

儿科癌症生物学和数据科学交叉领域的放射肿瘤学

• 批准号: 10712290
• 负责人: DAPHNE A. HAAS-KOGAN
• 金额: $ 164.5万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712290
• 关键词: Accounting; Address; Adult; Advisory Committees; Advocate; Anatomy; Artificial Intelligence; Award; Biological; Biological Markers; Biology; Boston; California; Cancer Biology; Cancer Center; Cells; Child; Childhood; Childhood Glioma; Childhood Solid Neoplasm; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Network; Collection; Communities; Comprehensive Cancer Center; Computational Biology; Core Facility; Credentialing; Daphne plant; Data; Data Science; Data Set; Development; Discipline; Doctor of Medicine; Doctor of Philosophy; Education; Elements; Evolution; External Beam Radiation Therapy; Extramural Activities; Face; Family; Funding; Future; General Population; Genetic; Heterogeneity; Image; Infrastructure; Infrequent Neoplasm; Institution; International; Investigational Therapies; Late Effects; Machine Learning; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical; Methodology; Mission; Modality; Molecular; Mutation; National Cancer Institute; National Clinical Trials Network; Neuroblastoma; Oncology; Outcome; Patient advocacy; Patients; Pediatric Neoplasm; Persons; Physics; Pilot Projects; Population; Positioning Attribute; Process; Productivity; Quality of life; Radiation; Radiation Oncologist; Radiation Oncology; Radiation therapy; Radiobiology; Radiogenomics; Radiopharmaceuticals; Records; Regimen; Research; Research Personnel; Research Project Grants; Resistance; Resources; Robin bird; Sampling; San Francisco; Scientist; Solid Neoplasm; Specific qualifier value; Specimen; Students; Sum; Technology; Testing; Toxic effect; Training; Training Programs; Tumor Tissue; Universities; Variant; Work; cancer cell; cancer genetics; cancer research center director; clinical material; cohort; data integration; data modeling; design; diffuse midline glioma; dosimetry; experience; genomic data; high risk; improved; insight; mathematical model; metaiodobenzylguanidine; multimodality; multiscale data; neoplastic cell; novel; outreach program; physical science; professor; programs; prospective; radiation during childhood; radiation resistance; radiation response; radioresistant; response; skills; spatiotemporal; standard of care; treatment response; tumor; tumor heterogeneity; tumor-immune system interactions

Project Summary Basic scientists and clinical investigators from Dana-Farber/Harvard Cancer Center (DF/HCC) join forces with their counterparts at University of California, San Francisco’s (UCSF) Helen Diller Family Comprehensive Cancer Center to propose a Harvard/UCSF ROBIN Center. Our Objective is to improve potency and selectivity of two key radiation modalities--external beam radiation and radiopharmaceuticals. A distinctive feature of our ROBIN Center is its selection of two clinically aggressive pediatric tumors--diffuse midline glioma (DMG) and high-risk neuroblastoma (NBL) – as scientific vehicles for the study plan. The genetic drivers of these two pediatric cancers are found also in more common adult solid tumors. Moreover, the low mutational burden of these pediatric cancers provides a clean genetic background for the “low N/high content” Molecular Characterization Trials (MCTs) specified by the ROBIN RFA. The malignant cells within DMG and NBL are heterogenous with respect to developmental stage. The central hypothesis of our study plan is that this developmental heterogeneity is echoed at the level of radiation-response mechanisms and enables radiation resistance. Our study plan features two research projects configured to test predictions of this hypothesis. Project 1 draws upon paired samples of pre-and post-radiotherapy tumor tissue from children treated prospectively with a uniform radiotherapy regimen to test the prediction that radiation selects for radioresistant intra-tumoral variants. Project 2 tests the prediction that 131I-MIBG therapy of aggressive neuroblastoma selects for intra-tumoral subtypes with unfavorable responses to treatment. Our ROBIN MCT provides resources needed to complete the objectives and specific aims of the two Projects. Multimodal analysis and mathematical modeling of data from the Projects and the MCT will be performed in a Clinical Artificial Intelligence and Imaging Core and a Molecular Data Science and Advanced Dosimetry Core. A Cross- Training Core and an Administrative Core will support scientific activities and serve also as the Center’s “outward face” to the broader scientific community and lay public. The Center will serve as a “value-added” component of the NCI’s extramural support mission by leveraging (i) P30 core facilities of DF/HCC and UCSF, (ii) a U54-funded DFCI Physical Sciences Oncology Center, and (iii) the NCI's Experimental Therapeutics Clinical Trials Network and National Clinical Trials Networks. Conversely, an NCI ROBIN award to the Harvard/UCSF Center would be “value-added” to the field of radiation oncology by catalyzing productive interactions between radiation biology, artificial intelligence, and data science – disciplines that are well-established in Boston and San Francisco but have never been applied coordinately to the problem of radioresistance. Center co-leads, Professors Daphne Haas-Kogan M.D. and Franziska Michor, Ph.D. have much experience in management of multi-investigator, multi-institutional research programs together with complementary skillsets in radiation oncology and advanced data science.

项目摘要 来自Dana-Farber/哈佛癌症中心(DF/HCC)的基础科学家和临床研究人员与 加州大学旧金山分校(UCSF)的海伦·迪勒家庭综合体 癌症中心提议建立哈佛/加州大学罗宾中心。我们的目标是提高效率和 两种关键的辐射方式--外束辐射和放射性药物的选择性。一种与众不同的 我们罗宾中心的特点是选择了两种临床上具有侵袭性的儿科肿瘤--弥漫性中线胶质瘤 (DMG)和高危神经母细胞瘤(NBL)--作为研究计划的科学载体。人类的基因驱动因素 这两种儿科癌症也可见于更常见的成人实体瘤。此外，低突变 这些儿科癌症的负担为低N/高含量分子提供了干净的遗传背景 由Robin RFA指定的特性试验(MCT)。DMG和NBL内的恶性细胞是 异质性的关于发育阶段的。我们研究计划的中心假设是 发育异质性在辐射反应机制的水平上得到响应，并使辐射成为可能 抵抗。我们的研究计划以两个研究项目为特色，旨在测试这一假说的预测。 项目1利用了来自接受治疗的儿童放射治疗前后肿瘤组织的配对样本。 前瞻性地采用统一的放射治疗方案来测试辐射选择用于放射抵抗的预测 肿瘤内变异。项目2验证131I-MIBG治疗侵袭性神经母细胞瘤的预测 选择治疗反应不佳的肿瘤内亚型。我们的Robin MCT提供了 完成这两个项目的目标和具体目的所需的资源。多模式分析和 来自项目和MCT的数据的数学建模将在临床人工设备中执行 智能和成像核心以及分子数据科学和高级剂量学核心。十字勋章- 培训核心和管理核心将支持科学活动，并作为中心的 “外向型”面向更广泛的科学界和公众。 该中心将通过以下方式作为NCI外部支持任务的“增值”部分 利用(I)DF/HCC和UCSF的P30核心设施，(Ii)由U54资助的DFCI物理科学肿瘤学 NCI的实验治疗学临床试验网络和国家临床试验 网络。相反，将NCI罗宾奖授予哈佛/加州大学旧金山分校中心将为这一领域带来“增值” 通过催化辐射生物学、人工智能和 数据科学-在波士顿和旧金山已经很成熟但从未被应用过的学科 协调解决辐射抵抗问题。中心联合负责人，Daphne Haas-Kogan医学博士和 Franziska Michor博士在多个调查员、多机构的管理方面有丰富的经验 研究计划以及辐射肿瘤学和高级数据科学方面的互补技能。