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.

项目概要 来自 Dana-Farber/Harvard Cancer Center (DF/HCC) 的基础科学家和临床研究人员携手合作 他们在加州大学旧金山分校 (UCSF) 海伦迪勒家庭综合中心的部门 癌症中心提议建立哈佛大学/加州大学旧金山分校罗宾中心。我们的目标是提高效力和能力。 两种关键辐射方式的选择性——外束辐射和放射性药物。 我们ROBIN中心的特色是选择了两种临床上具有侵袭性的儿童肿瘤——弥漫性中线胶质瘤 （DMG）和高风险神经母细胞瘤（NBL）——作为研究计划的遗传驱动因素。 这两种儿童癌症也存在于更常见的成人实体瘤中。 这些儿科癌症的负担为“低氮/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 我们研究计划的中心假设是： 发育异质性在辐射反应机制水平上得到回应，并使辐射成为可能 我们的研究计划包括两个研究项目，旨在检验这一假设的预测。 项目 1 利用来自接受治疗的儿童的放疗前和放疗后肿瘤组织的配对样本 前瞻性地采用统一的放疗方案来检验辐射选择抗辐射的预测 项目 2 测试了 131I-MIBG 治疗侵袭性神经母细胞瘤的预测。 我们的 ROBIN MCT 提供对治疗反应不良的肿瘤内亚型的选择。 完成两个项目的目标和具体目标所需的资源。 来自项目和 MCT 的数据的数学建模将在临床人工实验室中进行 智能和成像核心以及分子数据科学和高级剂量测定核心。 培训核心和行政核心将支持科学活动，并作为该中心的 面向更广泛的科学界和公众的“外在面孔”。 该中心将作为 NCI 校外支持任务的“增值”组成部分 利用 (i) DF/HCC 和 UCSF 的 P30 核心设施，(ii) U54 资助的 DFCI 物理科学肿瘤学 中心，以及 (iii) NCI 实验治疗临床试验网络和国家临床试验 在线下，哈佛/加州大学旧金山分校中心获得的 NCI ROBIN 奖将为该领域带来“增值”。 通过催化放射生物学、人工智能和放射肿瘤学之间的富有成效的相互作用来发展放射肿瘤学 数据科学——在波士顿和旧金山已经很成熟但从未得到应用的学科 中心共同领导者 Daphne Haas-Kogan 教授（医学博士）和 Franziska Michor 博士在多研究者、多机构的管理方面拥有丰富的经验 研究项目以及放射肿瘤学和先进数据科学方面的补充技能。