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Comparing the Efficacy of Deferoxamine or Amifostine Pre-Treatment In the Prevention of Osteoradionecrosis of the Murine Mandible
Brendan J. Alleyne, BS, Davood Varghai, MD, Ufuk Askeroglu, MD, Christy Gliniak, BS, Samantha Zwiebel, BA, Rachel Geisey, BS, Kathryn Tobin, BS, Jason Sohn, PhD, Charles Kunos, MD PhD, Valdir Colosi, PhD, Mitchell Machtay, MD, Arun K. Gosain, MD.
Case Western Reserve University, Cleveland, OH, USA.

PURPOSE:
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.
METHODS:
The right mandible of each rat 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 (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. Samples underwent histological analysis for the number of empty lacunae and the number of osteoblasts and osteoclasts present at 6 weeks.
RESULTS:
The difference between the right central incisor root area and the left was statistically significant for the Radiation-Only Group (p=0.00016). There was also a strongly significant difference between the right and left sides for the DFO and Radiation Group (p=2.58095E-09). The Combined Drug Group and Radiation Group also displayed a significant difference (p=0.00369). However, the AMFO and Radiation Group did not show a significant difference between teeth roots (p=0.15629).
CONCLUSION:
The drug groups 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. This study suggests that Amifostine may be more efficacious in preserving the tooth root and possibly in the prevention of osteoradionecrosis. We will pursue molecular analysis of inflammatory markers at time points which will correlate to the histological analysis.

Methods
Experimental
Group 1:
10 rats received fractionated radiation doses of 7 Gy per day for 5 consecutive days (35 Gy total) to the Right Mandible. The Left Mandible was used as a control. They received a local DFO injection every other day beginning 4 weeks prior to the first radiation dose
Experimental
Group 2:
Same radiation dose but given only AMFO subq injection 40 minutes before each radiation dose (total of 5 days)
Experimental
Group 3:
Same radiation dose with both drugs given (DFO 4 weeks before radiation and AMFO given 40 minutes before each dose)
Control Group 1:same as group 1 except without DFO
Control Group 2:same as group 2 except without AMFO
Control Group 3:same as group 3 except without radiation
Control Group 4:same as group 1 except without radiation
Control Group 5:same as group 2 except without radiation


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