The head and neck cancer patient who requires a partial resection of the mandible presents a difficult clinical problem. In many cases, the tissues have already been exposed to high doses of irradiation and so the reconstructive surgeon must work in a compromised tissue bed. The biologic basis for the timing of surgical repair either before or after irradiation has not been fully evaluated. Both clinical and experimental evidence suggest that better reconstructive results are obtained if surgery is performed soon after completion of irradiation when irradiation is done first; or irradiation is delayed when surgery is the initial procedure. A model system in which one can control many of the variables present in the human situation is advantageous. A nonspontaneously healing defect will be made in the rat mandible and either left unfilled or filled with demineralized bone powder (DBP). The healing, which is complete in a DBP-filled defect in an unirradiated bed, will be evaluated in irradiated and unirrradiated mandibles by calculating the percentage bone fill and the area of the defect at the time of sacrifice. The following studies are proposed: 1. using a single dose of 20 Gy, determination of optimal time both for irradiation after surgery (with irradiation on day 1, 3, 7, 14, 21, 35, or 42 after surgery), and for surgery 1 - 42 days after irradiation; 2. development of a dose-response curve in both the preoperative and postoperative irradiation groups for a single dose of 0 - 30 Gy at the time of optimal healing; 3. generation of dose-response and isoeffect curves and alpha/beta ratios for both groups using 0 - 10 fractions of 2 - 6 Gy up to 60 Gy; 4. histologically and histomorphometrically evaluate all of the groups using decalcified and undecalcified sections. The hypothesis that bone (which is usually a late responder to irradiation) becomes an early responding tissue if surgery is performed before irradiation will also be tested. The alpha/beta ratios and isoeffect curves of the preoperative and postoperative irradiation groups will be compared. Early responding tissue has a larger alpha/beta ratio and a flatter slope of the isoeffect curve, both of which are indicative of a lower repair capacity than that of late responding tissue which has a steeper slope and a smaller alpha/beta ratio.
