Spinal Cord Tolerance to Radiosurgical Dose Delivery

描述（由申请方提供）：脊柱放射外科的临床辐射剂量处方已升级至颅内放射外科目前可接受的水平，预期可增加脊柱肿瘤控制的持久性并减少肿瘤诱导的麻痹和疼痛，但椎骨在结构完整性完好的情况下可耐受的最大单次剂量尚不清楚，并且在当前处方中可能超过。目前正在进行一项研究，以确定接受脊柱放射外科治疗的猪中脊髓脊髓病的辐射剂量相关发病率，但辐射后遗症分析仅限于神经组织。一项同时进行的协同研究将通过研究辐射剂量相关的骨毒性及其对生物力学骨强度的影响，极大地扩展当前研究的实用性。放射治疗后椎体骨折风险的预测指标将通过三种先进成像模式（micro-CT、定量CT和PET）收集的数据以及临床前模型中的血清分析、骨组织形态计量学和生物力学压缩测试来了解。在放射外科手术后一年内，将对血流量、代谢活性、骨密度、微结构和骨转换的剂量依赖性变化进行表征，并将其与生物力学骨强度相关。所得数据将为以知情的方式逐步增加脊柱剂量提供合理的依据，并可能揭示辐射诱导的骨弱化发病机制，从而可以利用介入机会。结果将最终转化为脊柱癌患者获得最佳的生存机会，无疼痛，高质量的生活，同时保持非常低的发病率。 公共卫生相关性：脊柱放射外科的临床辐射剂量处方已升级至颅内放射外科目前可接受的水平，期望增加脊柱肿瘤控制的持久性并减少肿瘤诱导的瘫痪和疼痛，但椎骨在结构完整性完好的情况下可耐受的最大单次剂量未知，并且在当前处方中可能超过。本研究旨在探讨放射剂量相关的骨毒性及其对骨生物力学强度的影响。拟议的研究可能会导致放射治疗后椎体骨折风险的预测指标，并将揭示放射引起的骨弱化的发病机制，以便可以利用介入的机会。

DESCRIPTION (provided by applicant): Clinical radiation dose prescriptions for spinal radiosurgery have been escalated to levels currently accepted in intracranial radiosurgery with the expectation of increasing the durability of tumor control in the spinal column and reducing tumor induced paralysis and pain but the maximum single-dose a vertebra can tolerate with structural integrity intact is unknown and may be exceeded in current prescriptions. A study is currently underway to determine the radiation dose-related incidence of spinal cord myelopathy in swine that receive a spinal radiosurgery treatment but analysis of radiation sequelae is limited to neurologic tissue. A concurrent, synergistic study will dramatically expand the utility of the current study by investigating radiation dose-related bone toxicity and its affect on biomechanical bone strength. Predictive indicators of the risk of vertebral fracture following radiation therapy will be learned through data collected by three advanced imaging modalities (micro-CT, quantitative CT and PET) and by blood serum analysis, bone histomorphometry and biomechanical compression testing in a preclinical model. Dose-dependent changes in blood flow, metabolic activity, bone density, microarchitecture, and bone turnover will be characterized for a one year period after radiosurgery and will be correlated with biomechanical bone strength. Resulting data will provide a rational basis to escalate spinal dose in an informed manner and will likely reveal the radiation-induced pathogenesis of bone weakening so that interventional opportunities can be exploited. Results 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 rate of morbidity. PUBLIC HEALTH RELEVANCE: Clinical radiation dose prescriptions for spinal radiosurgery have been escalated to levels currently accepted in intracranial radiosurgery with the expectation of increasing the durability of tumor control in the spinal column and reducing tumor induced paralysis and pain but the maximum single-dose a vertebra can tolerate with structural integrity intact is unknown and may be exceeded in current prescriptions. A study is proposed to investigate radiation dose-related bone toxicity and its affect on biomechanical bone strength. The proposed study will likely lead to predictive indicators of the risk of vertebral fracture following radiation therapy and will reveal the radiation-induced pathogenesis of bone weakening so that interventional opportunities can be exploited.