Spinal Cord Tolerance to Radiosurgical Dose Delivery

描述(申请人提供)：脊柱放射外科的临床放射剂量处方已经升级到目前在颅内放射外科中可接受的水平，以期增加脊柱肿瘤控制的持久性，并减少肿瘤引起的瘫痪和疼痛，但在结构完整的情况下，椎体可以耐受的最大单次剂量尚不清楚，目前的处方可能会超过该剂量。目前正在进行一项研究，以确定接受脊髓放射外科治疗的猪的脊髓脊髓病与辐射剂量相关的发生率，但对辐射后遗症的分析仅限于神经组织。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，一项同时进行的协同研究将极大地扩展当前研究的用途。放射治疗后脊柱骨折风险的预测指标将通过三种先进的成像方式(微型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。血流量、代谢活动、骨密度、微结构和骨转换的剂量依赖性变化将在放射外科治疗后的一年内被表征，并将与生物力学骨强度相关。所获得的数据将为以知情的方式增加脊柱剂量提供合理的基础，并可能揭示辐射诱导的骨弱化的发病机制，以便利用干预机会。结果将最终转化为脊椎癌症患者获得最好的生存机会，在保持非常低的发病率的同时，获得无痛、高质量的生活。 公共卫生相关性：脊柱放射外科的临床放射剂量处方已经升级到目前颅内放射外科可接受的水平，以期增加脊柱肿瘤控制的持久性，并减少肿瘤引起的瘫痪和疼痛，但在结构完整的情况下，椎体可以耐受的最大单次剂量尚不清楚，目前的处方可能会超过这一剂量。本研究旨在探讨辐射剂量相关的骨毒性及其对骨生物力学强度的影响。这项拟议的研究可能会导致放射治疗后脊柱骨折风险的预测指标，并将揭示辐射诱导的骨质减弱的发病机制，从而可以利用介入机会。

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.