Spinal cord tolerance to single-fraction partial-volume irradiation: a swine model

To determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine.

A 5-cm-long cervical segment was irradiated in 38-47-week-old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. The radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord, resulting in a dose distribution with the 90%, 50%, and 10% isodose lines traversing the ipsilateral, central, and contralateral spinal cord, respectively. The dose was prescribed to the 90% isodose line. A total of 26 pigs were stratified into eight dose groups of 12-47 Gy. The mean maximum spinal cord dose was 16.9 ± 0.1, 18.9 ± 0.1, 21.0 ± 0.1, 23.0 ± 0.2, and 25.3 ± 0.3 Gy in the 16-, 18-, 20-, 22-, and 24-Gy dose groups, respectively. The mean percentage of spinal cord volumes receiving ≥ 10 Gy for the same groups were 43% ± 3%, 48% ± 4%, 51% ± 2%, 57% ± 2%, and 59% ± 4%. The study endpoint was motor neurologic deficit determined by a change in gait during a 1-year follow-up period.

A steep dose-response curve was observed with a median effective dose for the maximum dose point of 20.0 Gy (95% confidence interval, 18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histologic change. All the minipigs with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side, with relative sparing of the gray matter. The histologic findings were unremarkable in the minipigs with normal neurologic status.

Our results have indicated that for a dose distribution with a steep lateral gradient, the pigs had a lower median effective dose for paralysis than has been observed in rats and more closely resembles that for rats, mice, and guinea pigs receiving uniform spinal cord irradiation.