Spinal Cord Tolerance to Radiosurgical Dose Delivery

描述(申请人提供)：脊柱肿瘤影响大量的人，导致丧失能力的疼痛、感觉和运动障碍、括约肌功能丧失和脊椎塌陷。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能够达到以前仅限于大脑的精度和剂量一致性，为抗击脊椎癌症的个人创造了新的选择。对脊髓附近的病变进行单次高剂量照射的机会引起了人们对脊髓的放射敏感性和潜在的脊髓病的新的担忧。关于脊髓对放射外科剂量传递的耐受性，人们知之甚少。在放射外科剂量传递中，陡峭的剂量梯度只导致脊髓的一小部分接受高剂量。因此，临床医生经常被迫开出比显示的剂量低得多的剂量，以导致对颅内病变的高控制率。啮齿类动物的放射模型表明，小体积和部分脊髓照射具有深刻的剂量-体积效应，灵长类动物模型表明，经过标准疗程的放射治疗后，脊髓经历了显着的修复，但没有研究以与临床放射外科实践相关的方式结合这些因素。建议进行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从头开始和再次治疗的情景。具体地说，本研究旨在确定：a)使用剂量率、野大小和剂量分布等临床相关治疗参数接受脊柱放射外科治疗的猪的剂量相关脊髓病发病率；b)在完成脊柱转移瘤标准临床放射治疗方案(300cGy10次)后一年接受脊髓放射外科治疗的猪的剂量相关发病率；c)3Tesla磁共振成像和光谱分析是否对放射外科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！数据将使用概率分析进行分析，以建立剂量-效应曲线，并计算与50%瘫痪发生率相关的剂量。这项研究将提供基本的知识，最终将转化为脊椎癌症患者在保持非常低的致残性副作用的同时，获得无痛、高质量的生存机会。

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.