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.
