Muscle injury following experimental intraoperative irradiation.

The paraaortic region of beagle dogs was irradiated to 15 to 55 Gy intraoperative irradiation, 10 to 47.5 Gy intraoperative irradiation following 50 Gy external beam irradiation in 25 fractions, or 50 to 80 Gy external beam irradiation in 30 fractions. Six MeV electrons were used for intraoperative irradiation, and external beam irradiation was done using photons from a 6 MV linear accelerator. The psoas muscle in the irradiation field was examined histomorphometrically 2 or 5 years after irradiation. The percentage of muscle fibers and capillaries decreased, whereas the percentage of connective tissue increased with increased dose for both intraoperative irradiation only and intraoperative irradiation plus external beam irradiation. The dose causing a 50% decrease in the percentage of muscle fibers was 21.2 Gy and 33.8 Gy at 2 and 5 years, respectively, after intraoperative irradiation alone, and 22.9 Gy and 25.2 Gy at 2 and 5 years, respectively, after intraoperative irradiation combined with 50 Gy external beam irradiation. The ED50 for severe vessel lesions was 19.2 Gy and 25.8 Gy at 2 and 5 years, respectively, after intraoperative irradiation alone and 16.0 Gy and 18.0 Gy at 2 and 5 years, respectively, after intraoperative irradiation combined with 50 Gy external beam irradiation. External beam irradiation alone caused a slight decrease in percentage of muscle fibers with increased dose, and vessel lesions were infrequent or mild. Radiation-induced muscle injury was characterized by loss of muscle fibers, decreased fiber size, severe vessel lesions, hemorrhage, inflammation, coagulation necrosis, and fibrosis. These histopathologic characteristics distinguish this muscle injury from that caused by neurogenic atrophy. These data indicate that radiation-induced muscle injury most likely was caused by injury of the supporting vasculature. The lesions produced were largely a function of the single intraoperative dose rather than the external beam fractionated doses. Furthermore, it appears that 20 to 25 Gy intraoperative irradiation combined with 50 Gy external beam irradiation may be near the maximum tolerated dose by sublumbar musculature and its supporting vasculature.

Ureteral injury following experimental intraoperative radiation.

Beagle dogs were randomized to receive a range of total dose delivered in three different protocols. Sixteen dogs received external beam radiation therapy (EBRT), 32 dogs received intraoperative irradiation (IORT), and 32 dogs received combinations of external beam radiation therapy and intraoperative irradiation. A sublumbar field was irradiated which always included the left ureter. Dogs were observed for 5 years; sequential excretory urograms were done at 6 months, and 1 and 5 years. Morphometric analysis of tissues were also done. The canine ureter tolerated 17.5 Gy intraoperative irradiation with no evidence of injury and 25 Gy intraoperative irradiation with a low probability of injury. The ED50 for radiographic abnormalities was 32.9 Gy. When 50 Gy external beam radiation therapy was given prior to intraoperative irradiation, the ureter tolerated 10 Gy intraoperative irradiation with no evidence of injury and 17.5 Gy with a low probability of injury. The ED50 was 29 Gy intraoperative irradiation after EBRT. The external beam radiation therapy had little effect on the ureter when given alone or prior to intraoperative irradiation. Clinical signs of renal disease occurred only in dogs who had received bilateral ureteral irradiation intraoperatively at doses of 32.5 Gy intraoperative irradiation and 25 Gy intraoperative irradiation after external beam radiation therapy. Histologic evidence suggests that the chronic injury of the ureter expressed at 5 years is of vascular etiology. The early injury may be due to ulceration of the epithelium.