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COMPARING THE EFFICACY OF DEFEROXAMINE OR AMIFOSTINE PRE-TREATMENT IN THE PREVENTION OF OSTEORADIONECROSIS OF THE MURINE MANDIBLE
Presenter: Brendan J Alleyne, BS
Co-Authors: Varghai D; Askeroglu U; Gliniak C; Tobin K; Zwiebel S; Gosain AK
Case Western Reserve University School of Medicine

Introduction: Osteoradionecrosis (ORN) of the mandible and facial bones is a significant problem for patients who are treated for head and neck cancer. Evidence suggests that deferoxamine (DFO) and amifostine (AMFO) may have beneficial roles in the prevention and treatment of ORN. DFO has been shown to have a vasculogenic effect while Amifostine has been shown to prevent cytotoxicity and apoptosis. We hypothesize that DFO and AMFO will have beneficial effects in the prevention and treatment of ORN in a rat model, especially when used in combination.

Method: The right mandible of 40 rats was irradiated with 5 fractions of 7 Gy (35 Gy total), the bioequivalent dose to humans treated for Head and Neck Cancer. CT scans were taken 6 weeks following the final radiation dose. Image-J (NIH free-ware) was used to calculate the percentage area of decreased calcification within the tooth root of the right hemi-mandibles as compared to the left side controls. Decreased calcification served as a marker for ionizing damage.

Result: The difference between the right central incisor root area and the left was strongly statistically significant for the Radiation-Only Group (p=1.57E-26). There was also a significant difference for the DFO and Radiation Group (p=1.5E-14). The Combined Drug and Radiation Group also displayed a significant difference (p=2.03E-11). The AMFO and Radiation Group showed the least drastic difference between tooth roots (p=0.00015).

Conclusion: The drug groups all appear to prevent the full manifestation of ORN with the bio-equivalent dose of 35 Gy given over 5 doses. The loss of the odontoblast layer of the tooth root appears to be protected by DFO and combined therapies. However, AMFO alone appeared to offer greater bone protection by more strongly preventing the observed decalcification. Lastly, these results may implicate areas for further study in radioprotective therapy in which the field overlies the mandible and facial skeleton.


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