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

项目摘要 恶性神经胶质瘤能够渗透到远离原发肿瘤的大脑偏远区域， 不断挑战有效治疗的发展，以及这些肿瘤患者的预后 仍然很差，中位生存期以数周而不是数年来衡量。尽管放射治疗在 虽然放射治疗在延长这些患者的生命方面发挥着重要作用，但CNS中的放射副作用仍然是毁灭性的， 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肿瘤。 这种疾病的各个方面。本申请旨在展示粒子治疗的一种新的放射生物学元素 以超高剂量率递送，这可以降低CNS中的正常组织毒性，并允许安全使用 与常规治疗相比， 放射治疗我们小组最近的研究表明，新方法在实验上是可行的。我们 我提议用啮齿动物的神经胶质瘤模型来测试我们的新想法。此外，我们还将研究结果 辐射后的形态、认知和病理变化，以量化新方法的毒性， 我们希望它比传统疗法的毒性更低。总的来说，这些目标将提供 临床前数据和新的生物学知识，以推动人类临床试验的治疗， 改善恶性神经胶质瘤和其它脑肿瘤治疗。

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.