Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX 75390-9183, USA.
Int J Radiat Oncol Biol Phys. 2011 Apr 1;79(5):1302-9. doi: 10.1016/j.ijrobp.2010.10.052. Epub 2010 Dec 22.
Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat has demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.
近年来，脊柱放射外科的临床应用迅速增加，但对于人体脊髓对单次照射的耐受程度知之甚少。相比之下，自 20 世纪 70 年代以来，单次脊髓耐受的临床前研究一直在进行。已经研究了场长度、剂量率、不均匀剂量分布和再照射的影响。本综述总结了临床前模型中单次脊髓耐受的文献，重点介绍了实际的临床意义。在多个小动物和大动物模型中，对均匀照射的研究结果令人惊讶地一致。对大鼠不均匀剂量分布的广泛研究表明存在显著的剂量-体积效应，而来自一项猪研究的初步结果则相互矛盾。临床前脊髓剂量-体积研究表明，剂量分布比受照体积更为关键，这表明剂量-体积直方图分析或绝对体积限制都不能有效地预测并发症。再照射数据很少，但来自豚鼠、大鼠和猪的研究结果与脊髓具有较大修复能力的假设一致。脊髓研究中观察到的现象背后的机制尚不清楚，剂量反应模型预测结果的能力也存在差异，这突显了进一步研究的必要性。动物研究为放射敏感性的现象和机制提供了深入了解，但只有通过临床试验才能发现动物研究的真正意义。
