The tolerance of primate spinal cord to re-irradiation

This study was designed to assess the tolerance of the cervical spinal cord of rhesus monkeys to re-irradiation. This information is essential for treatment recommendations in previously irradiated patients.

Control animals received a single course of treatment to total doses of 70.4 Gy, 77.0 Gy, or 83.6 Gy in daily fractions of 2.2 Gy. Twelve asymptomatic animals that received 70.4 Gy were re-irradiated two years later to cumulative doses of 83.6, 92.4, or 101.2 Gy. Another group of 15 animals received 44 Gy and two years later were re-irradiated to cumulative doses of 83.6, 92.4, 101.2, or 110 Gy. The clinical endpoint was myeloparesis. A complete necropsy was performed in all animals when myeloparesis manifested or at the end of observation period.

Only two of the 12 asymptomatic animals of the 70.4 Gy dose-response study group and two of the 15 animals that had received 44 Gy initially developed myelopathy within two years of re-irradiation. The ED50 value of the single-course irradiation was 76.1 +/- 1.9 Gy, while the extrapolated ED50 for retreatment after 44 Gy was > or = 110 Gy. The lesions of the two symptomatic animals that received 70.4 Gy initially were mixtures of white matter and vascular lesions similar to those observed after single course irradiation. However, both symptomatic animals given 44 Gy initially had hemorrhagic infarcts in the white matter.

The results of this study indicate that substantial recovery of occult injuries induced by the initial 44 Gy had occurred within two years. The difference between the types of lesions observed after a single course and re-irradiation suggests that vascular injury may recover less efficiently or at slower rate than white matter damage. The dependence of the extent of recovery on the initial dose and the time course of such recovery in primates are being investigated.