Gok Beril, McGirt Matthew, Sciubba Daniel M, Ayhan Selim, Bydon Ali, Witham Timothy F, Wolinsky Jean-Paul, Gokaslan Ziya L
Department of Neurosurgery, The Johns Hopkins University, Baltimore, Maryland, USA.
Neurosurgery. 2008 Aug;63(2):346-51; discussion 351. doi: 10.1227/01.NEU.0000320424.50804.C8.
The optimal management of spinal column metastatic disease is controversial. Furthermore, the literature lacks an accurate animal model to study the efficacy of surgical treatment options for spinal column metastases. We compared the efficacy of surgery, radiotherapy, or surgery plus adjuvant radiotherapy in a rat model of metastatic epidural spinal cord compression.
Thirty-two Fischer 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the vertebral body of L6. Animals were randomly assigned to receive one of four treatments (n = 8 per group) 7 days after tumor implantation: 1) control: no treatment; 2) external beam radiation therapy (XRT) (total 20 Gy in 400-cGy daily fractions); 3) surgery: L6 vertebral corpectomy, tumor resection, and polymethyl methacrylate reconstruction; and 4) surgery + XRT: corpectomy and tumor resection followed by XRT (total 20 Gy in 400-cGy daily fractions) 72 hours after surgery. Hind-limb function was tested daily after treatment using the Basso-Beattie-Bresnahan (BBB) scale (range, 1-21).
All animals (n = 32) demonstrated normal hind-limb function (BBB score, 21) on posttreatment Day 1. The XRT, surgery, and surgery + XRT groups all experienced a delay in onset of paresis versus the control group. Compared to the XRT group, the surgery group demonstrated greater median BBB scores on Days 3 (21 versus 20, P = 0.02) through 9 (12 versus 8, P = 0.002) after treatment. Compared with the surgery group, the surgery + XRT group demonstrated even greater median BBB scores on Days 6 (21 versus 19, P = 0.0008) through 11 (16 versus 8, P = 0.0001) after treatment. Median time to loss of ambulation (BBB <or= 7) was greatest in the surgery + XRT group (15 d) when compared with the surgery (12 d, P = 0.001), XRT (9 d, P = 0.001), or control groups (7 d, P = 0.0005).
In a rat model of metastatic epidural spinal cord compression, decompressive surgery followed by radiotherapy yielded the greatest efficacy in the prevention of neurological decline when compared with surgery or radiotherapy alone. Radiotherapy alone attenuated neurological decline but was the least efficacious treatment in this model. These results support this animal model as an effective platform to investigate novel interventions for metastatic spine tumors.
脊柱转移性疾病的最佳治疗方案存在争议。此外，文献中缺乏用于研究脊柱转移瘤手术治疗方案疗效的精确动物模型。我们在转移性硬膜外脊髓压迫的大鼠模型中比较了手术、放疗或手术加辅助放疗的疗效。
32只Fischer 344大鼠经腹途径在L6椎体植入CRL-1666乳腺癌细胞系。肿瘤植入7天后，动物被随机分配接受四种治疗之一（每组n = 8）：1）对照组：不治疗；2）外照射放疗（XRT）（共20 Gy，每日分次剂量400 cGy）；3）手术：L6椎体次全切除术、肿瘤切除术及聚甲基丙烯酸甲酯重建术；4）手术 + XRT：次全切除术和肿瘤切除术后72小时进行XRT（共20 Gy，每日分次剂量400 cGy）。治疗后每天使用Basso-Beattie-Bresnahan（BBB）量表（范围1 - 21）测试后肢功能。
所有动物（n = 32）在治疗后第1天均表现出正常的后肢功能（BBB评分21）。与对照组相比，XRT组、手术组和手术 + XRT组的轻瘫发作均出现延迟。与XRT组相比，手术组在治疗后第3天（21对20，P = 0.02）至第9天（12对8，P = 0.002）的BBB评分中位数更高。与手术组相比，手术 + XRT组在治疗后第6天（21对19，P = 0.0008）至第11天（16对8，P = 0.0001）的BBB评分中位数更高。与手术组（12天，P = 0.001）、XRT组（9天，P = 0.001）或对照组（7天，P = 0.0005）相比，手术 + XRT组的中位行走丧失时间（BBB≤7）最长（15天）。
在转移性硬膜外脊髓压迫的大鼠模型中，与单独手术或放疗相比，减压手术联合放疗在预防神经功能衰退方面疗效最佳。单独放疗可减轻神经功能衰退，但在该模型中是疗效最差的治疗方法。这些结果支持该动物模型作为研究转移性脊柱肿瘤新干预措施的有效平台。
