EFFECTS OF INTRAOPERATIVE IRRADIATION AND INTRAOPERATIVE HYPERTHERMIAON CANINE SCIATIC-NERVE - NEUROLOGIC AND ELECTROPHYSIOLOGIC STUDY

Purpose: Late radiation injury to peripheral nerve may be the Limiting factor in the clinical application of intraoperative radiation therap y (IORT). The combination of IORT with intraoperative hyperthermia (IO HT) raises specific concerns regarding the effects on certain normal t issues such as peripheral nerve, which might be included in the treatm ent field. The objective of this study was to compare the effect of IO RT alone to the effect of IORT combined with IOHT on peripheral nerve in normal beagle dogs. Methods and Materials: Young adult beagle dogs were randomized into five groups of three to five dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy to 5 cm of surgically exposed right sciatic nerve using 6 MeV electrons and six groups of four to fi ve dogs each received IORT doses of 0, 12, 16, 20, 24, or 28 Gy simult aneously with 44 degrees C of IOHT for 60 min. IOHT was performed usin g a water circulating hyperthermia device with a multichannel thermome try system on the surgically exposed sciatic nerve. Neurologic and ele ctrophysiologic examinations were done before and monthly after treatm ent for 24 months. Electrophysiologic studies included electromyograph ic (EMG) examinations of motor function, as well as motor nerve conduc tion velocities studies. Results: Two years after treatment, the effec tive dose for 50% complication (ED(50)) for limb paresis in dogs expos ed to IORT only was 22 Gy. The ED(50) for paresis in dogs exposed to I ORT combined with IOHT was 15 Gy. The thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more prominent changes such as EMG abnormalities, decrease in conduction velocity and amplitude o f the action potential, and complete conduction block in dogs that rec eived the combination of IORT and IOHT. The latency to development of peripheral neuropathies was shorter for dogs exposed to the combined t reatment. Conclusion: The probability of developing peripheral neuropa thies in a large animal model was higher for IORT combined with IOHT, than for IORT alone. The dose required to produce the same level of la te radiation injury to the sciatic nerve was reduced by a factor of 1. 5 (TER) if IORT was combined with 44 degrees C of IOHT for 60 min.