Ultra-high-dose-rate proton therapy for malignant glioma

恶性胶质瘤的超高剂量率质子治疗

• 批准号: 9913488
• 负责人: John G. Eley
• 金额: $ 18.12万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-11 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913488
• 关键词: Affect; Anatomy; Behavioral; Biological; Bioluminescence; Biophysics; Blood Vessels; Brain; Brain Neoplasms; Brain region; Cells; Chemotherapy and/or radiation; Childhood Malignant Brain Tumor; Clinical; Clinical Trials; Cognitive; Cranial Irradiation; Data; Demyelinations; Development; Diagnosis; Disease; Dose; Dose-Rate; Drug Delivery Systems; Electron Beam; Elements; Excision; Face; France; Genetic; Glioma; Hippocampus (Brain); Human; Image; Immunohistochemistry; Impaired cognition; Inflammatory Response; Knowledge; Lead; Life; Lung; Magnetic Resonance Imaging; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Measures; Metabolic; Metastatic malignant neoplasm to brain; Methods; Microscopic; Mission; Monitor; Morphology; Mus; Necrosis; Neoplasm Metastasis; Nervous System Trauma; Neurobiology; Neurologic; Neurosciences; Normal tissue morphology; Operative Surgical Procedures; Outcome; Pathologic; Patients; Physics; Physiological; Play; Primary Neoplasm; Protons; Quality of life; Radiation; Radiation Dose Unit; Radiation Oncology; Radiation induced damage; Radiation therapy; Radiosurgery; Rattus; Recurrence; Research; Risk; Rodent Model; Role; Scanning; Sterilization; Survivors; Switzerland; System; Testing; Toxic effect; Treatment Efficacy; United States National Institutes of Health; Work; Xenograft procedure; behavior test; cancer cell; cancer imaging; clinical implementation; cognitive change; cognitive function; combat; conventional therapy; disorder control; effective therapy; efficacy testing; electron radiation; expectation; imaging study; improved; irradiation; neoplastic cell; neurogenesis; neuroinflammation; outcome forecast; particle therapy; pre-clinical; prevent; proton beam; proton therapy; response; side effect; tool; translation to humans; tumor; tumor growth

PROJECT SUMMARY The ability of malignant gliomas to infiltrate remote regions of the brain, far from their primary tumor mass, has continually challenged the development of an effective therapy, and prognosis for patients with these tumors remains poor, with median survival measured in weeks rather than years. Although radiotherapy plays a critical role in extending life for these patients, radiation side effects in CNS can still be devastating and greatly affect quality of life, which prevents the use of higher, cancer-sterilizing doses of radiation to treat the invasive aspects of this disease. This application seeks to demonstrate a new radiobiologic element of particle therapy delivered at ultra-high dose rates, which may reduce normal tissue toxicity in CNS and allow the safe use of higher radiation doses to greater volumes of potentially involved brain, compared to conventional radiotherapies. Recent studies by our group demonstrate the new method is experimentally feasible. We propose to test our new ideas using rodent models of glioma. Furthermore, we will investigate the resulting morphologic, cognitive, and pathologic changes after irradiation to quantify the toxicity of the new method, which we expect to be lower than toxicities of conventional therapies. Collectively, these aims will provide the preclinical data and new biologic knowledge needed to advance therapy towards human clinical trials to improve treatment of malignant glioma and other brain tumors.

项目概要 恶性神经胶质瘤能够浸润远离原发肿瘤块的大脑偏远区域， 不断挑战有效疗法的开发以及这些肿瘤患者的预后 仍然很差，中位生存期以周而不是几年来衡量。尽管放射治疗起着至关重要的作用 尽管对于延长这些患者的生命具有重要作用，但中枢神经系统的放射副作用仍然是毁灭性的，并极大地影响 生活质量，防止使用更高的癌症消毒剂量的辐射来治疗侵入性癌症 这种疾病的各个方面。该应用旨在展示粒子治疗的新放射生物学元素 以超高剂量率输送，这可以减少中枢神经系统中正常组织的毒性，并允许安全使用 与传统方法相比，对更大体积的潜在受累大脑的辐射剂量更高 放射治疗。我们小组最近的研究表明，这种新方法在实验上是可行的。我们 建议使用神经胶质瘤的啮齿动物模型来测试我们的新想法。此外，我们将调查由此产生的 辐射后的形态、认知和病理变化来量化新方法的毒性， 我们预计其毒性低于传统疗法。总的来说，这些目标将提供 推进人体临床试验治疗所需的临床前数据和新的生物学知识 改善恶性神经胶质瘤和其他脑肿瘤的治疗。