COMBINED EFFECTS OF FRACTIONATION AND RADIOPROTECTANT IN SPARING OF RADIATION INDUCED PHYSEAL DAMAGE

Timothy A. Damron, M.D., Robert M. Tamurian, B.S., Joseph A. Spadaro, Ph.D., Leatha A. Damron, B.S., Department of Orthopedic Surgery, SUNY Health Science Center at Syracuse Orthopedic Laboratory, SUNY Health Science Center at Syracuse

Introduction: The purpose of this study was to determine the combined effects on sparing of longitudinal bone growth by both fractionation and chemical radioprotection.

Methods: Twenty-four weanling four week old Sprague-Dawley rats were randomized into four treatment groups (n=6 animals/group) for comparison with three previously reported treatment and control groups of identical size. The distal femur and proximal tibia in the right leg of each animal was exposed to a therapeutic x-irradiation dose (17.5 Gy in 3 or 5 fractions) with the contralateral left leg as control. In two of the groups, amifostine (100 mg/kg) was administered intraperitoneally twenty minutes prior to radiation exposure. Six weeks later, growth was calculated based upon measurement of the bone lengths.

Results: In our earlier work, the single radiation dose of 17.5 Gy reduced net growth in overall limb length by a mean 58.3% in the treated leg; amifostine administration significantly (p=0.001) reduced the mean percent growth loss to 43.3%. In this study, fractionation of the 17.5 Gy radiation dose into three and five equal fractions significantly (p<0.01) reduced the mean percent overall limb growth loss to 18.35% (range 2-44%, SD 15.56%) and 23.82% (range 14-36%, SD 9.72%), respectively. The addition of amifostine to the three and five fraction radiotherapy groups brought the mean percent overall limb growth loss to 18.25% (range 10-25%, SD 8.73%) and 10.67% (range 8-19%, SD 5.44%), respectively. The growth loss resulting from the combination of amifostine and five fraction radiation was statistically significantly lower than that from five fraction radiation alone.

Discussion: The combination of fractionation and radioprotection with amifostine produced the greatest mean reduction in growth lost due to radiation effects. Further ongoing research will examine the mechanism of radioprotectant damage and radioprotectant effects of fractionation and amifostine as well as novel radioprotectants.

*Supported by grants from the Children’s Miracle Network and the Orthopedic Research and Education Foundation.