Effects of intraoperative irradiation (IORT) and intraoperative hyperthermia (IOHT) on canine sciatic nerve: Histopathological and morphometric studies

Purpose/Objective: Peripheral neuropathies have emerged as the major dose-l imiting complication reported after intraoperative radiation therapy (IORT) . The combination of IORT with hyperthermia may further increase the risk o f peripheral nerve injury. The objective of this study was to evaluate hist opathological and histomorphometric changes in the sciatic nerve of dogs, a fter IORT with or without hyperthermia treatment. Methods and Materials: Young adult beagle dogs were randomized into five gr oups of 3-5 dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy, Si x groups of 4-5 dogs each received IORT doses of 12, 16, 20, 24, or 28 Gy s imultaneously with 44 degrees C of intraoperative hyperthermia (IOHT) for 6 0 min. One group of dogs acted as hyperthermia-alone controls. Two years af ter the treatment, dogs were euthanized, and histopathological and morphome tric analyses were performed. Results: Qualitative histological analysis showed prominant changes such as focal necrosis, mineralization, fibrosis, and severe fiber loss in dogs wh ich received combined treatment. Histomorphometric results showed a signifi cantly higher decrease in axon and myelin and small blood vessels, with a c orresponding increase in connective tissue in dogs receiving IORT plus hype rthermia treatment, The effective dose for 50% of nerve fiber loss (ED50) i n dogs exposed to IORT only was 25.3 Gy, The ED50 for nerve fiber loss in d ogs exposed to IORT combined with IOHT was 14.8 Gy, The thermal enhancement ratio (TER) was 1.7. Conclusion: The probability of developing peripheral neuropathies in a larg e animal model is higher when IORT is combined with IOHT, when compared to IORT application alone. To minimize the risk of peripheral neuropathy, clin ical treatment protocols for the combination of IORT and hyperthermia shoul d not assume a thermal enhancement ratio (TER) to be lower than 1.5, (C) 19 99 Elsevier Science Inc.