Risk factors and dose–effect relationship for osteoradionecrosis after hyperfractionated and conventionally fractionated radiotherapy for oral cancer

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Abstract
A high frequency of osteoradionecrosis after hyperfractionated radiotherapy (RT) of head and neck tumours led to a detailed analysis of risk factors in the dental, surgical, and radiotherapeutic areas. 168 patients with oral cancer were analysed retrospectively. 19% of them had been irradiated primarily and 81% postoperatively. 116 patients received a total dose mostly ranging from 60 Gy to 70 Gy to the ICRU 29 reference point (daily single dose 2 Gy). 52 patients were treated hyperfractionally with two daily fractions of 1.2 Gy per day, 4 h minimum apart and a total dose 82.8 Gy. Dental findings could be evaluated in 126 patients. Factors were checked for prognostic significance for osteoradionecrosis (ORN). Dose dependency was computed using a PROBIT analysis. Dental status before radiotherapy was generally poor (mean 11/32 teeth present, of these 1 was dead, 2.4 carious, 2.4 loose, 0.3 destroyed). On average, six teeth (range 0-27 teeth) had to be extracted. In one-third of the patients bone surgery was necessary. ORN occurred in 8.6% of the patients treated conventionally but in 22.9% of those treated hyperfractionally (p = 0.029). Biologically effective dose (p = 0.032) and deep paradontitis (p = 0.034) proved to be significant risk factors for ORN. PROBIT analysis showed a steadily rising dose dependency of the ORN frequency after conventional radiotherapy. Using total doses up to 70 Gy the frequency of ORN was 8.6%. Dose escalation using hyperfractionation led to an intolerable ORN frequency (22.9%) where a short interfraction interval was a significant factor. The use of this dose fractionation was therefore discontinued in 1992.