Bagley Carlos A, Bookland Markus J, Pindrik Jonathan A, Ozmen Tolga, Gokaslan Ziya L, Wolinsky Jean-Paul, Witham Timothy F
Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-7713, USA.
J Neurosurg Spine. 2007 Sep;7(3):323-7. doi: 10.3171/SPI-07/09/323.
Spinal column metastatic disease affects thousands of cancer patients every year. Radiation therapy frequently represents the primary treatment for this condition. Despite the enormous clinical impact of spinal column metastatic disease, the literature currently lacks an accurate animal model for testing the efficacy of irradiation on spinal column metastases.
After anesthesia was induced, female Fischer 344 rats underwent a transabdominal approach to the ventral vertebral body (VB) of L-6. A 2- to 3-mm-diameter bur hole was drilled for the implantation of a section of CRL-1666 breast adenocarcinoma. After the animals had recovered from the surgery, they underwent fractionated, single-port radiotherapy beginning on postoperative Day 7. Each group of animals underwent five daily fractions of radiation treatment. Group I animals received a total dose of 10 Gy in 200-cGy daily fractions, Group II animals received a total dose of 20 Gy in 400-cGy daily fractions, and Group III animals received a total dose of 30 Gy in 600-cGy daily fractions. A control group of rats with implanted VB lesions did not receive radiation. To test the effects of radiation toxicity alone, additional rats without implanted tumors received radiation treatments in the same fractions as the rats with tumors. Hindlimb function in all rats was rated before and after radiation treatment using the Basso-Beattie-Bresnahan locomotor rating scale. Histological analysis of spinal cord and vertebral column sections was performed after each animal's death.
Functional assessments demonstrated a statistically significant delay in the onset of paresis between the three treatment groups and the control group (tumor implanted but no radiotherapy). The rats in the three treatment groups, however, did not exhibit any significant differences related to hindlimb function. A dose-dependent relationship was found for the percentage of animals who had become paralyzed at the time of death, with all members of the control group and no members of the 30-Gy group exhibiting paralysis. The results of this study do not indicate any overall survival benefit for any level of radiation dose.
These findings demonstrate the efficacy of focal spinal irradiation in delaying the onset of paralysis in a rat metastatic spine tumor model, but without a clear survival benefit. Because of the dose-related toxicity observed in the rats treated with 30 Gy, this effect was most profound for the 20-Gy group. This finding parallels the observed clinical course of spinal column metastatic disease in humans and provides a basis for the future comparison of novel local and systemic treatments to augment the observed effects of focal irradiation.
每年有数千名癌症患者受到脊柱转移性疾病的影响。放射治疗常常是这种疾病的主要治疗方法。尽管脊柱转移性疾病具有巨大的临床影响，但目前文献中缺乏用于测试放疗对脊柱转移瘤疗效的精确动物模型。
对雌性Fischer 344大鼠进行麻醉后，经腹 approach至L-6椎体腹侧。钻一个直径2至3毫米的钻孔，用于植入一段CRL-1666乳腺腺癌。动物术后恢复后，从术后第7天开始进行分次单端口放疗。每组动物接受5次每日放疗。I组动物每日分次接受200厘戈瑞，总剂量为10 Gy；II组动物每日分次接受400厘戈瑞，总剂量为20 Gy；III组动物每日分次接受600厘戈瑞，总剂量为30 Gy。植入椎体病变的对照组大鼠未接受放疗。为单独测试放射毒性的影响，另外未植入肿瘤的大鼠接受与有肿瘤大鼠相同分次的放射治疗。在放疗前后，使用Basso-Beattie-Bresnahan运动评分量表对所有大鼠的后肢功能进行评分。每只动物死亡后，对脊髓和脊柱切片进行组织学分析。
功能评估表明，三个治疗组与对照组（植入肿瘤但未放疗）之间在轻瘫发作时间上存在统计学显著延迟。然而，三个治疗组的大鼠在后肢功能方面未表现出任何显著差异。发现死亡时瘫痪动物的百分比存在剂量依赖性关系，对照组所有动物均瘫痪，而30 Gy组无动物瘫痪。本研究结果未表明任何剂量水平的放疗对总体生存有任何益处。
这些发现证明了局部脊柱照射在大鼠转移性脊柱肿瘤模型中延迟瘫痪发作的疗效，但无明显生存益处。由于在接受30 Gy治疗的大鼠中观察到剂量相关毒性，这种效应在20 Gy组最为显著。这一发现与人类脊柱转移性疾病的临床病程相似，并为未来比较新型局部和全身治疗以增强局部照射的观察效果提供了基础。
