Dose-volume effects in the rat cervical spinal cord after proton irradiation

Purpose: To estimate dose-volume effects in the rat cervical spinal cord with protons. Methods and Materials: 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. (C) 2002 Elsevier Science Inc.