Dose-volume effects in the rat cervical spinal cord after proton irradiation. 2002
OBJECTIVE To estimate dose-volume effects in the rat cervical spinal cord with protons. METHODS Wistar rats were irradiated on the cervical spinal cord with a single fraction of unmodulated protons (150-190 MeV) using the shoot through method, which employs the plateau of the depth-dose profile rather than the Bragg peak. Four different lengths of the spinal cord (2, 4, 8, and 20 mm) were irradiated with variable doses. The endpoint for estimating dose-volume effects was paralysis of fore or hind limbs. RESULTS The results obtained with a high-precision proton beam showed a marginal increase of ED50 when decreasing the irradiated cord length from 20 mm (ED50 = 20.4 Gy) to 8 mm (ED50 = 24.9 Gy), but a steep increase in ED50 when further decreasing the length to 4 mm (ED50 = 53.7 Gy) and 2 mm (ED50 = 87.8 Gy). These results generally confirm data obtained previously in a limited series with 4-6-MV photons, and for the first time it was possible to construct complete dose-response curves down to lengths of 2 mm. At higher ED50 values and shorter lengths irradiated, the latent period to paralysis decreased from 125 to 60 days. CONCLUSIONS Irradiation of variable lengths of rat cervical spinal cord with protons showed steeply increasing ED50 values for lengths of less than 8 mm. These results suggest the presence of a critical migration distance of 2-3 mm for cells involved in regeneration processes.