Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Human Oncology, University of Wisconsin, Madison, Wisconsin.
Int J Radiat Oncol Biol Phys. 2019 Jul 15;104(4):845-851. doi: 10.1016/j.ijrobp.2019.03.044. Epub 2019 Apr 4.
This study was performed to determine the dose-related incidence of neuropathy from single-session irradiation of the C6-C8 spinal nerves using a pig model and to test the hypothesis that the spinal nerves and spinal cord have the same tolerance to full cross-sectional irradiation.
Twenty-five Yucatan minipigs received study treatment. Each animal underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 1.5-cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. Pigs were distributed into 5 groups with prescription doses of 16 (n = 7), 18 (5), 20 (5), 22 (5), or 24 (3) Gy with corresponding maximum nerve doses of 17.3, 19.5, 21.6, 24.1, and 26.2 Gy. The neurologic status of all animals was followed for approximately 52 weeks by serial electrodiagnostic examination and daily observation of gait. Histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff staining was performed on bilateral spinal nerves and the spinal cord.
Marked gait change was observed in 15 of the 25 irradiated pigs. Affected animals presented with a limp in their left front limb, and electromyography demonstrated evidence of denervation in C6 and C7 innervated muscles. Probit analysis showed the ED for gait change after irradiation of the spinal nerves to be 19.7 Gy (95% confidence interval, 18.5-21.1). The latency for all responding pigs was 9 to 15 weeks after irradiation. All symptomatic pigs had demyelination and fibrosis in their irradiated nerves, whereas contralateral nerves and spinal cord were normal.
The ED for symptomatic neuropathy after full cross-sectional irradiation of the spinal nerves was found to be 19.7 Gy. The dose response of the C6-C8 spinal nerves is not significantly different from that of full cross-sectional irradiation of the spinal cord as observed in companion studies.
本研究旨在通过猪模型确定单次照射 C6-C8 脊神经引起的神经病变与剂量的相关性，并验证脊神经与脊髓具有相同的全横断照射耐受能力这一假说。
25 头尤卡坦微型猪接受了研究治疗。每头动物在接受计算机断层扫描和磁共振成像进行治疗计划后，接受单次立体定向消融放疗。目标是左侧 C6、C7 和 C8 脊神经 1.5 厘米长。猪被分为 5 组，处方剂量分别为 16（n=7）、18（n=5）、20（n=5）、22（n=5）或 24（n=3）Gy，相应的最大神经剂量为 17.3、19.5、21.6、24.1 和 26.2 Gy。通过连续电诊断检查和每天观察步态，大约在 52 周内对所有动物的神经状态进行随访。用卢索快速蓝/过碘酸希夫染色对双侧脊神经和脊髓进行石蜡包埋切片的组织病理学检查。
25 只照射猪中有 15 只出现明显的步态改变。受影响的动物表现为左前肢跛行，肌电图显示 C6 和 C7 支配肌肉有去神经支配的证据。概率分析显示，脊神经照射后出现步态改变的 ED 为 19.7 Gy（95%置信区间，18.5-21.1）。所有有反应的猪在照射后 9 至 15 周出现潜伏期。所有有症状的猪在照射的神经中都有脱髓鞘和纤维化，而对侧神经和脊髓正常。
全横断照射脊神经后出现症状性神经病的 ED 为 19.7 Gy。与配套研究中观察到的全横断脊髓照射相比，C6-C8 脊神经的剂量反应没有显著差异。
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