Kinsella T J, DeLuca A M, Barnes M, Anderson W, Terrill R, Sindelar W F
Radiation Oncology Branch, National Cancer Institute, Bethesda, MD 20205.
Int J Radiat Oncol Biol Phys. 1991 Apr;20(4):697-701. doi: 10.1016/0360-3016(91)90011-r.
Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers and perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds (wt 20-25 kg) received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy. These experimental data suggest that intraoperative doses of less than 20 Gy may not result in clinically significant peripheral nerve injury with follow-up of 3.5 years. Longer (5 yrs) follow-up with planned sacrifice of the remaining dogs is scheduled to assess any late peripheral nerve damage.
在术中放疗的临床应用中，外周神经的放射性损伤是一种剂量限制性毒性，尤其是对于盆腔和腹膜后肿瘤。接受20 - 25 Gy剂量的人类术中放疗相关外周神经病变表现为治疗后6 - 9个月开始出现的混合性运动感觉障碍。在先前一项关于术中放疗相关腰骶丛神经病变的实验研究中，报告了术中剂量（20 - 75 Gy范围）与后肢麻痹发作时间（术中放疗后1 - 12个月）之间大致呈反比线性关系。照射神经的主要组织学病变是大神经纤维丧失和神经周纤维化，无明显血管损伤。在人类照射神经中也发现了类似的组织学变化。为了在同一大型动物模型中评估较低剂量术中放疗对外周神经的损伤，将四组成年美国猎狐犬（体重20 - 25 kg）的右侧腰骶丛和坐骨神经用9 MeV电子给予10、15或20 Gy的剂量。左侧腰骶丛和坐骨神经被排除在术野之外，以便每只动物作为自身对照。治疗后，每月进行一次完整的神经学检查、肌电图和神经传导研究，持续1年。在第2年和第3年每月进行神经学检查，而在此随访期间每3个月进行肌电图和神经传导研究。随访时间大于或等于42个月时，接受10或15 Gy术中放疗的狗没有显示出任何外周神经损伤的临床或实验室证据。然而，接受20 Gy的所有四只狗在术中放疗后8、9、9和12个月出现了右后肢麻痹。这些实验数据表明，术中剂量小于20 Gy在3.5年的随访中可能不会导致临床上显著的外周神经损伤。计划对其余的狗进行更长时间（5年）的随访并实施安乐死，以评估是否有任何晚期外周神经损伤。
