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 Dana-Farber/Harvard Cancer Center（DF/HCC）的基础科学家和临床研究人员与 他们在加利福尼亚大学旧金山（UCSF）海伦·迪勒（Helen Diller）家庭综合的对手 癌症中心提议哈佛/UCSF罗宾中心。我们的目标是提高效力和 两种关键辐射方式的选择性 - 外束辐射和放射性药物。一个独特的 罗宾中心的特征是它选择了两种临床上侵略性的小儿肿瘤 - 扩散中线胶质瘤 （DMG）和高风险神经母细胞瘤（NBL） - 作为研究计划的科学工具。遗传驱动因素 这两种儿科癌症也在更常见的成年实体瘤中发现。而且，低突变 这些小儿癌的负担为“低N/高含量”分子提供了干净的遗传背景 Robin RFA指定的表征试验（MCT）。 DMG和NBL中的恶性细胞是 关于发育阶段的异基。我们研究计划的核心假设是 发育异质性在辐射响应机制的水平上回荡，并启用辐射 反抗。我们的研究计划是两个研究项目，该项目配置为测试该假设的预测。 项目1借鉴了接受治疗的儿童的后放射治疗前后的配对样品 前瞻性采用均匀放疗方案，以测试辐射选择放射线的预测 穆斯内变体。项目2测试了131i-MIBG侵袭性神经母细胞瘤治疗的预测 选择对治疗反应不利的肿瘤内亚型。我们的罗宾MCT提供 完成两个项目的目标和具体目标所需的资源。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造中进行 智能和成像核心以及分子数据科学和晚期剂量测定核心。穿过- 培训核心和行政核心将支持科学活动，并作为中心的 对更广泛的科学界的“外表”和公开。 该中心将作为NCI的“增值”组成部分的“增值”组成部分 DF/HCC和UCSF的利用（I）P30核心设施，（ii）U54资助的DFCI物理科学肿瘤学 中心和（iii）NCI的实验治疗临床试验网络和国家临床试验 网络。相反，授予哈佛/UCSF中心的NCI Robin奖将“增值”到现场 通过催化辐射生物学，人工智能和 数据科学 - 波士顿和旧金山良好建立的学科，但从未应用 协调地解决放射线的问题。中心共同领导，教授达芙妮·哈斯·科根（Daphne Haas-Kogan M.D.）和 Franziska Michor博士在管理多机构的管理方面有很多经验 研究计划以及辐射肿瘤学和高级数据科学领域的完整技能。