A dose response analysis of injury to cranial nerves and/or nuclei following proton beam radiation therapy.

The low tolerance of the central nervous system (CNS) limits the radiation dose which can be delivered in the treatment of many patients with brain and head and neck tumors. Although there are many reports concerning the tolerance of the CNS, few have examined individual substructures of the brain and fewer still have had detailed dose information. This study has both. A three dimensional planning system was used to develop the combined proton beam/photon beam treatments for 27 patients with skull-base tumors. The cranial nerves and their related nuclei were delineated on the planning CT scans and the radiation dose to each was determined from three dimensional dose distributions. In the 594 CNS structures (22 structures/patient in 27 patients), there have been 17 structures (in 5 patients) with clinically manifest radiation injury, after a mean follow-up time of 74 months (range 40-110 months). From statistical analyses, dose is found to be a significant predictor of injury. Using logistic regression analysis, we find that, for each cranial nerve, at 60 Cobalt Gray Equivalent (CGE) the complication rate is 1% (0.5-3% with 95% confidence) and that the 5% complication rate occurs at 70 CGE (64-81 CGE with 95% confidence). The slope of the dose response curve (at 50%) is 3.2 (2.2-5.4 with 95% confidence). No significant relationship between dose and latency period for nerve injury was found.