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Efficacy of Radioprotection in the Prevention of Radiation-Induced Craniofacial Bone Growth Inhibition

Forrest, Christopher R. M.D., M.Sc.; O'Donovan, David A. M.B., F.R.C.S.(Plast.); Yeung, Ivan Ph.D.; Zeman, Vlado Ph.D.; Scala, Giorgio La M.D.; Neligan, Peter C. M.D.; Pang, Cho Y. Ph.D.

Plastic and Reconstructive Surgery: April 1, 2002 - Volume 109 - Issue 4 - p 1311–1323
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It has been reported that radiotherapy-induced craniofacial deformities can occur in 66 to 100 percent of survivors of childhood head and neck cancers. Recent interest in the effectiveness of radioprotectors in the protection of normal tissue against radiation injury led us to investigate a possible role of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition. Therefore, the objective of this study was to use the radioprotective agent amifostine (Ethyol, WR-2721) as a probe to determine the effectiveness of radioprotection in the prevention of radiation-induced craniofacial bone growth inhibition after single-dose orthovoltage radiation to the infant rabbit orbital-zygomatic complex. Sevenweek-old male New Zealand white rabbits were randomized into three groups (n = 10 each): group 1, 0 Gy (sham radiation); group 2, 35-Gy single-dose orthovoltage radiation; and group 3, 35-Gy single-dose orthovoltage radiation and amifostine (300 mg/kg intravenously, given 20 minutes before radiation). Serial radiographs and computed tomographic scans were obtained for cephalometric analysis, bone volume, and bone density measurements until skeletal maturity at 21 weeks. Significant (p < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were observed after 35-Gy radiation compared with nonirradiated controls. No significant differences were noted between groups in cephalometric analysis of the nontreated (nonirradiated) left orbital-zygomatic complex, indicating no crossover effect from the radiation beam. However, pretreatment with amifostine, 20 minutes before 35-Gy radiation, resulted in significant (p < 0.05) preservation of linear bone growth, bone volume, and bone mineral density in the rabbit orbital-zygomatic complex compared with controls. This study demonstrated for the first time the effectiveness of a radioprotector in the prevention of radiation-induced craniofacial bone growth inhibition, and it paves the way for investigation into the pathogenic mechanism and prevention of radiotherapy-induced craniofacial deformities. (Plast. Reconstr. Surg. 109: 1311, 2002.)

Toronto, Ontario, Canada

From the Division of Plastic Surgery, The Hospital for Sick Children Centre for Craniofacial Care and Research, The Hospital for Sick Children Research Institute; the Department of Clinical Physics, Ontario Cancer Institute, Princess Margaret Hospital; and the Division of Plastic Surgery, University Health Network, University of Toronto. Received for publication May 13, 2001; revised June 15, 2001.

Presented in part at the 45th Annual Meeting of the Plastic Surgery Research Council, in Seattle, Washington, on May 19, 2000.

Christopher R. Forrest, M.D., M.Sc. The Hospital for Sick Children Center for Craniofacial Care and Research Suite 5430 555 University Avenue Toronto, Ontario M5G 1X8, Canadachristopher.forrest@sickkids.on.ca

©2002American Society of Plastic Surgeons