WE‐AB‐207B‐10: On Spinal Nerve Toxicity from Single‐Session SAbR in Pigs and the Translation of Small Animal NTCP Models

Abstract

Purpose:The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose‐tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single‐session irradiation to the pig spinal nerves exhibit a similar dose‐tolerance as that of the spinal cord and that a dose‐length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data.Methods:To date, 16 of 25 Yucatan minipigs have received single‐session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left‐sided C6‐C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose‐response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose‐response data and to preliminary peripheral nerve response data was evaluated through residual analysis.Results:No rodent‐derived dose‐response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long‐length irradiated spinal cord data well, with the more serial‐like models fitting best. Preliminary data on the short‐length irradiation suggests no length effect exists, disproving our hypothesis.Conclusion:Direct application of small‐animal NTCP models to pig data suggests dose‐length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low‐to‐mid dose levels in the penumbral region will improve this match.This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).