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

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.

Osteoradionecrosis of the Mandibula in Patients Treated with Different Fractionations

“…In using hyperfractionation, an interfraction interval > 4.5 h is important: an intermediate evaluation of the RTOG 83-13 study [4,8] and the experience of Niewald et al [21] show an increase of the incidence of ON after hyperfractionation with an interfraction interval of ≤ 4.5 h ( Table 2). In a statistics by Niewald et al [21], the incidence of ON after hyperfractionation using two fractions of 1.2 Gy per day on 5 days per week and a total dose of 82 Gy, the incidence of ON was 22.9% with an interval between the two fractions of 4 h in the majority of patients (Table 2). In our own experience as well as according to the data of Mendenhall et al and Parsons et al [19,22] and the randomized fractionation study RTOG 90-03 [9], the risk of ON is < 5% after a total dose between 72 and 80 Gy and an interfraction interval of 6 h.…”

Risk Factors and Dose–Effect Relationship for Mandibular Osteoradionecrosis in Oral and Oropharyngeal Cancer Patients

“…There are no clear studies on the risk factors of ORN, and although factors such as smoking, drinking, tumor characteristics, oral hygiene, and traumatic events such as surgery and radiation have been implicated in the literature, it is apparently affected by many complex factors (9)(10)(11)(12). From the perspective of radiation therapy, it is known that radiation dose is a major cause of ORN; the higher radiation dose, the higher the risk of ORN (6,7,10,13,14) To investigate the risk factors for ORN of the mandible, this study analyzed patients who had received radiation therapy for oral and oropharyngeal cancer, with the aim of determining the dose-effect relationship between radiation dosage and the development of ORN.…”

Osteoradionecrosis of the cervical vertebrae in patients irradiated for head and neck cancers

“…In one study of 168 patients with oral cancer treated with hyperfractionated radiation therapy or conventional radiation therapy, the incidence of ORN was higher with hyperfractionated regimens (22.9% vs. 8.6%). 8 In the present report, three patients received chemotherapy concurrently with radiation therapy of at least one course. Concurrent chemoradiation therapy increases not only local control but also overall survival compared to radiation therapy alone.…”