Spinal Cord Tolerance to Radiosurgical Dose Delivery

描述（由申请人提供）：脊柱肿瘤影响大量人群，导致失能性疼痛、感觉和运动缺陷、括约肌功能丧失和椎体塌陷。图像引导立体定向放射外科（SRS）技术的进步使脊柱和脊柱旁肿瘤的照射具有准确性和剂量一致性，以前仅限于脑部，为脊柱癌症患者提供了新的选择。对脊髓附近病变进行单次高剂量照射的机会引起了人们对脊髓放射敏感性和脊髓病可能性的新关注。关于脊髓对放射外科剂量递送的耐受性知之甚少，其中陡峭的剂量梯度导致只有一小部分脊髓接受高剂量。因此，临床医生经常被迫开出远低于那些显示导致颅内病变控制率高的剂量。啮齿动物的放射治疗模型表明，小体积和部分脊髓照射存在深刻的剂量-体积效应，灵长类动物模型表明，在标准放射治疗过程中脊髓经历了显著的修复，但没有研究将这些因素与临床放射外科实践相关的方式结合起来。一项脊髓耐受性研究将纳入脊髓SRS患者通常经历的重新治疗和再治疗方案。具体来说，本研究旨在确定：A)使用临床相关的剂量率、场大小和剂量分布等治疗参数，接受脊柱放射外科治疗的猪的脊髓病的剂量相关发病率；B)在完成脊髓转移的标准临床放射治疗方案一年后接受脊柱放射手术治疗的猪中脊髓病的剂量相关发病率（300 cGy × 10）；C)如果3特斯拉磁共振成像和波谱对放射术后生物过程的早期表达敏感，从而区分可逆和不可逆损伤，并提示潜在的干预措施。广达电脑!将使用概率分析对数据进行分析，以建立剂量效应曲线，并计算与50%麻痹发生率相关的剂量。这项研究将提供必要的知识，最终将转化为脊柱癌患者获得无痛，高质量生活的最佳生存机会，同时保持极低水平的致残副作用。

DESCRIPTION (provided by applicant): Tumors of the spine affect a large number of people causing incapacitating pain, sensory and motor deficits, loss of sphincter function and vertebral collapse. Advances in image-guided stereotactic radiosurgery (SRS) techniques have enabled the irradiation of spinal and paraspinal neoplasms with an accuracy and dose conformality previously restricted to the brain creating new options for individuals fighting cancers of the spine. The opportunity to irradiate lesions adjacent to the spinal cord to very high doses in a single fraction has raised new concerns regarding the radiosensitivity of the cord and the potential for myelopathy. Little is known regarding the tolerance of the spinal cord to a radiosurgical dose delivery in which the steep dose gradients result in only a fraction of the cord receiving a high dose. Therefore, clinicians are often compelled to prescribe doses much lower than those shown to result in a high rate of control for intracranial lesions. A radiotherapy model in rodents suggests there is a profound dose-volume effect for small volume and partial cord irradiation and a primate model suggests the spinal cord undergoes significant repair following a standard course of radiotherapy but no study has combined these factors in a manner relevant to clinical radiosurgery practice. A spinal cord tolerance study is proposed that will incorporate both de novo and retreatment scenarios commonly experienced by humans treated with spinal SRS. Specifically, this study is intended to determine: A) the dose-related incidence of myelopathy in swine that receive a spinal radiosurgery treatment using clinically relevant treatment parameters of dose rate, field size and dose distribution; B) the dose related incidence of myelopathy in swine that receive a spinal radiosurgery treatment delivered one year following completion of a standard clinical radiation regimen for spinal metastases (300 cGy times 10); and C) if 3 Tesla magnetic resonance imaging and spectroscopy are sensitive to the early expression of post-radiosurgery biological processes so as to discriminate between reversible and irreversible damage and to indicate potential interventions. Quanta! data will be analyzed using probit analysis to establish dose-effect curves, and to calculate the doses associated with a 50% incidence of paralysis. This study will provide essential knowledge that will ultimately translate into spine cancer patients receiving the best chance for survival with a pain free, high quality of life while maintaining a very low level of disabling side effects.