The effect of hyperfractionation on spinal cord response to radiation.

The T10-L2 level of the spinal cord of C3Hf mice was irradiated using a conventionally fractionated regimen of 2.0 Gy once daily or a hyperfractionated regimen of 1.2 Gy twice daily separated by 8 hr. After a fractionated dose of 24-60 Gy given by either regimen, a top-up dose of 15 Gy was given. Hind limb strength was then measured weekly for 15 months. The time to onset of paralysis was inversely associated with the total dose. Overall, the spinal cord was not spared by hyperfractionation to the extent predicted by the modified Ellis power law or the linear-quadratic model. The threshold dose for the development of paralysis was higher in the hyperfractionated than in the conventionally fractionated group. However, the latent period for paralysis and the dose producing hind limb paralysis in 50% of the mice (ED50) were not significantly different between the two regimens. The continuation of the process of sublethal damage (SLD) repair in the spinal cord beyond 8 hr after irradiation may have influenced these results. The slow component of SLD repair should be considered in the design of hyperfractionated or accelerated radiation therapy schedules for clinical use.