Extent and kinetics of recovery of occult spinal cord injury
Extent and kinetics of recovery of occult spinal cord injury
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DOI：
10.1016/s0360-3016(01)01599-1
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发表时间：
2001-07-15
影响因子：
7
通讯作者：
Price, RE
中科院分区：
文献类型：
--
作者：
Ang, KK;Jiang, GL;Price, RE
目的：为了获得临床上有用的定量数据的范围和动力学的恢复隐匿性放射损伤的灵长类动物脊髓后，通常给药的选择性放射剂量为44 GS，在约2戈伊每fraction.Methods和材料：一组56只猕猴被分配到两个放射疗程的颈部和上胸段脊髓，在2.2戈伊每部分。所有猴的初始疗程剂量为44戈伊。间隔1年（n = 16）或2年（n = 20）后再照射剂量为57.2戈伊，间隔2年（n = 4）或3年（n = 14）后再照射剂量为66戈伊。2只动物在再照射前发生髓内肿瘤，因此未接受第二疗程。研究终点为脊髓切除，主要表现为下肢无力和平衡下降，发生在再照射后2.5年内，并辅以脊髓组织学检查。所获得的数据进行了分析沿着与数据从以前的研究解决单疗程的宽容，和数据从一个初步的研究reirradiation tolerances.Results：只有4的45只猴子完成所需的观察期（2-2.5年后再照射，3-5.5年的总）开发脊髓。数据显示，44戈伊引起的隐性损伤在第一年内基本恢复，并建议在1至3年内进一步恢复。用模型拟合数据，假设所有（单疗程和再照射）剂量-反应曲线平行，在5%发病率（D-5）水平下，1年、2年和3年后的恢复估计值分别为初始剂量的33.6戈伊（76%）、37.6戈伊（85%）和44.6戈伊（101%）。最保守的估计，使用一个模型，其中假设在初始照射后1 - 3年没有恢复，并且组合再照射曲线不一定平行于单疗程曲线，仍然显示出相当于26.8戈伊（61%）的总体恢复。有症状的猴子的脊髓一贯显示混合物的白色物质坏死和血管损伤，但大多数无症状的动物的脊髓没有表现出明显的病变检测通过光学microscopic.Conclusion：结合分析与以往研究的数据产生了有力的证据表明，脊髓有很大的能力，以恢复从隐性辐射损伤引起的一个共同规定的选择性剂量。这一发现加强了选择性使用放射治疗来治疗先前照射过的组织或晚期复发的第二原发肿瘤的理论基础。然而，在应用定量实验数据时应谨慎，因为这些实验的随访时间仅限于再照射后2-2.5年，而人类脊髓病病例偶尔会在更长的潜伏期后发生。由于组织间的长期恢复存在很大差异，因此在处方治疗时也应考虑其他有风险组织的耐受性。(C)2001 Elsevier Science Inc.
Purpose: To obtain clinically useful quantitative data on the extent and kinetics of recovery of occult radiation injury in primate spinal cord, after a commonly administered elective radiation dose of 44 GS, given in about 2 Gy per fraction.Methods and Materials: A group of 56 rhesus monkeys was assigned to receive two radiation courses to the cervical and upper thoracic spinal cord, given in 2.2 Gy per fraction. The dose of the initial course was 44 Gy in all monkeys. Reirradiation dose was 57.2 Gy, given after 1-year (n = 16) or 2-year (n = 20) intervals, or 66 Gy, given after 2-year (n = 4) or 3-year (n = 14) intervals. Two animals developed intramedullary tumors before reirradiation and, therefore, did not receive a second course. The study endpoint was myeloparesis, manifesting predominantly as lower extremity weakness and decrease in balance, occurring within 2.5 years after reirradiation, complemented by histologic examination of the spinal cord. The data obtained were analyzed along with data from a previous study addressing single-course tolerance, and data from a preliminary study of reirradiation tolerance.Results: Only 4 of 45 monkeys completing the required observation period (2-2.5 years after reirradiation, 3-5.5 years total) developed myeloparesis. The data revealed a substantial recovery of occult injury induced by 44 Gy within the first year, and suggested additional recovery between 1 and 3 years. Fitting the data with a model, assuming that all (single course and reirradiation) dose-response curves were parallel, yielded recovery estimates of 33.6 Gy (76%), 37.6 Gy (85%), and 44.6 Gy (101%) of the initial dose, after 1, 2, and 3 years, respectively, at the 5% incidence (D-5) level. The most conservative estimate, using a model in which it was assumed that there was no recovery between 1 and 3 years following initial irradiation and that the combined reirradiation curve was not necessarily parallel to the single-course curve, still showed an overall recovery equivalent to 26.8 Gy (61%). The spinal cords of symptomatic monkeys consistently revealed a mixture of white matter necrosis and vascular injury, but the majority of spinal cords of asymptomatic animals did not exhibit overt lesions detectable by light microscopy.Conclusion: Combined analysis with the data of the previous studies yielded firm evidence that the spinal cord has a large capacity to recover from occult radiation injury induced by a commonly prescribed elective dose. This finding strengthens the rationale for selective use of radiotherapy to treat second primary tumors arising in previously irradiated tissues or late recurrences. However, some caution should be exercised in applying quantitative experimental data, because the length of follow-up in these experiments was limited to 2-2.5 years after reirradiation, whereas human myelopathy cases occasionally occur after longer latency. Because there is a large variation in long-term recovery among tissues, the tolerance of other tissues at risk should also be taken into account in prescribing therapy. (C) 2001 Elsevier Science Inc.