Re-irradiation tolerance of rat spinal cord to fractionated X-ray doses

Abstract

Experiments were performed to assess the re-irradiation fractionation sensitivity in the rat cervical spinal cord. Animals were given initially three daily fractions of 9 Gy representing 75% of tolerance at the ED 50 level. After an interval of 20 weeks, they were re-irradiated with graded doses of X-ray in single, 2, 5, 10 and 20 daily fractions, or a single retreatment top-up dose of 12.8 Gy (equivalent to 80% of retreatment tolerance) followed by doses in 1, 2, 4, 10 and 20 daily fractions. The end-point was paralysis of the forelimbs secondary to white matter necrosis. Latent periods to paralysis ranged from 188 to 245 days from initial irradiation, or from 48 to 105 days from re-irradiation. For a given fractionated retreatment schedule, shorter latent times were observed in animals re-irradiated to higher total doses. The re-irradiation ED 50 values for single, 2, 5, 10 and 20 fractions were 14.0 (95% CI 13.3, 14.2), 20.5 (19.9, 21.2), 29.1 (28.0, 30.1), 36.3 (35.1, 37.4) and 47.8 Gy (46.2, 48.3), respectively. For re-irradiations with a 12.8 Gy top-up dose followed by doses in single, 2, 4 and 20 fractions, the retreatment ED 50 values excluding the 12.8 Gy top-up dose were 4.5 (95% CI 3.0, 5.4), 6.5 (5.6, 7.3), 7.0 (5.0, 8.1) and 10.9 Gy (8.9, 12.5), respectively. Direct fit of the linear-quadratic (LQ) model to the data gave similar α β values of 3.07 Gy (95% CI 2.30, 3.95) and 3.34 Gy (95% CI 1.94, 4.74), respectively, p = 0.6, for the retreatment experiments without and with top-up doses. This fractionation sensitivity during retreatment compares well with that of previously un-irradiated animals, α β value of 2.41 Gy for fraction sizes down to 2 Gy/fraction. It is concluded that there is significant long-term recovery of radiation damage in rat spinal cord, and that previous radiation damage to a level of 75% of tolerance does not change the capacity for repair of sublethal damage when the spinal cord is re-irradiated with fractionated doses of X-ray at 20 weeks.