Aortic wall injury following intraoperative irradiation

The type, extent, and probability of vasculopathy in canine abdominal aortas were determined 5 years after large single radiation doses given intraoperatively (IORT) either alone or with fractionated doses of external beam irradiation (EBRT) to compare with the response following EBRT only. Young adult beagle dogs were used. For IORT, a 5 x 8 cm electron applicator was used to deliver 6 MeV electrons to the paraaortic region. For EBRT of the paraaortic region, 6 MV photons were given in variable total doses in 30 fractions in 6 weeks. For the combination, variable IORT doses were given following an EBRT dose of 50 Gy given in 2 Gy fractions in 5 weeks. Necropsies were performed 4 to 5 years after irradiation. Transverse sections of the aorta were examined for lesions. Probit analyses were done to determine the dose with a 50% probability to cause severe lesions of the aorta 5 years after treatment. The most severe lesions were variably organized thrombi which occupied at least a third of the luminal area or intimal surface of the aorta. Six dogs with thrombi had dissecting aneurysms. That occurred at doses as low as 25 Gy IORT plus 50 Gy EBRT (1 of 4 dogs). The doses with a 50% probability for causing aneurysms and/or severe thromboses of the aorta were 35 Gy IORT (95% C.I., 29 to 46 Gy) and 27 Gy IORT plus 50 Gy EBRT (95% C.I., 20-40 Gy). No large thrombi or aneurysms were observed 5 years after EBRT to doses as high as 80 Gy. Comparison of the ED50s for IORT alone to that of IORT combined with EBRT indicated that 50 Gy given in 25 fractions had the impact of about 8 Gy IORT. Based on the response of younger adult dogs it appears that IORT doses greater than 30 Gy alone or 20 Gy IORT combined with 50 Gy EBRT would be accompanied by a significant risk of life threatening lesions of the aorta. This is in contrast with several earlier reports indicating that the tolerance dose of canine aorta was 50 Gy IORT.