Spinal Cord Tolerance to Radiosurgical Dose Delivery

描述（由申请人提供）：脊柱肿瘤影响许多人，引起失能性疼痛、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椎旁肿瘤的辐射具有以前仅限于大脑的准确性和剂量适形性，为脊柱癌症患者创造了新的选择。 在一次分割中以非常高的剂量照射邻近脊髓的病变的机会已经引起了关于脊髓的放射敏感性和脊髓病的可能性的新的关注。 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仅一部分脊髓接收高剂量。 因此，临床医生经常被迫开出远低于颅内病变控制率高的剂量。 啮齿类动物的放疗模型表明，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，脊髓在标准放疗过程后发生显著修复，但没有研究将这些因素以与临床放射外科实践相关的方式结合起来。 提出了一项脊髓耐受性研究，该研究将纳入接受脊髓SRS治疗的人类通常经历的新发和再治疗情况。 具体而言，本研究旨在确定：A）使用剂量率、射野大小和剂量分布的临床相关治疗参数接受脊柱放射外科治疗的猪中脊髓病的剂量相关发病率; B）接受脊柱放射外科治疗的猪中脊髓病的剂量相关发病率，所述脊柱放射外科治疗在完成脊柱转移的标准临床放射方案后一年递送（300 cGy × 10）;和C）如果3特斯拉磁共振成像和光谱学对放射外科手术后生物过程的早期表达敏感，以便区分可逆和不可逆损伤并指示潜在的干预。 广达将使用概率单位分析来分析数据，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，最终转化为脊柱癌患者获得最佳的生存机会，获得无疼痛，高质量的生活，同时保持非常低的致残副作用水平。

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.