Brachial Plexus Tolerance to Single-Session Stereotactic Ablative Radiotherapy (SAbR): A Pig Model

Abstract Purpose The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. Methods and Materials Ten Yucatan minipigs underwent CT and MR imaging for treatment planning followed by single-session stereotactic ablative radiotherapy (SAbR). A 2.5cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in three groups with prescription doses of 16 (n=3), 19 (4), and 22Gy (3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. Results Seven of the ten pigs developed motor deficit to the front limb of the irradiated side with a latency from 5–8 weeks following irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3Gy for neurologic deficit, but the number of animals is insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histological lesions to the left-sided plexus consistent with radiation-induced neuropathy. Conclusions The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5cm length of the brachial plexus cords was determined to be 19.3Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.