Extent and kinetics of recovery of occult spinal cord injury

Purpose: To obtain clinically useful quantitative data on the extent and ki netics 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, give n in 2.2 Gy per fraction. The dose of the initial course was 44 Gy in all m onkeys. Reirradiation dose was 57.2 Gy, given after 1-year (n = 16) or 2-ye ar (n = 20) intervals, or 66 Gy, given after 2-year (n = 4) or 3-year (n = 14) intervals. Two animals developed intramedullary tumors before reirradia tion and, therefore, did not receive a second course. The study endpoint wa s myeloparesis, manifesting predominantly as lower extremity weakness and d ecrease in balance, occurring within 2.5 years after reirradiation, complem ented by histologic examination of the spinal cord. The data obtained were analyzed along with data from a previous study addressing single-course tol erance, 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 ye ars. Fitting the data with a model, assuming that all (single course and re irradiation) 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, a fter 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 ther e was no recovery between 1 and 3 years following initial irradiation and t hat the combined reirradiation curve was not necessarily parallel to the si ngle-course curve, still showed an overall recovery equivalent to 26.8 Gy ( 61%). The spinal cords of symptomatic monkeys consistently revealed a mixtu re 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 oc cult radiation injury induced by a commonly prescribed elective dose. This finding strengthens the rationale for selective use of radiotherapy to trea t second primary tumors arising in previously irradiated tissues or late re currences. However, some caution should be exercised in applying quantitati ve experimental data, because the length of follow-up in these experiments was limited to 2-2.5 years after reirradiation, whereas human myelopathy ca ses occasionally occur after longer latency. Because there is a large varia tion in long-term recovery among tissues, the tolerance of other tissues at risk should also be taken into account in prescribing therapy. (C) 2001 El sevier Science Inc.