Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: Patterns of fractionation study of radiobiology

Purpose : To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for carcinoma of the tonsil. Methods and Materials : A retrospective analysis was made of the results in 676 patients treated with a spectrum of fractionation regimens in nine centers during the years 1976–1985. Only severe (Grades 3–4) late complications were analyzed. Purpose : With more than 5 years follow-up, it was found that total dose was a factor for all three types of compliations, but that in other respects, the radiobiology of late-(>3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Dose per fraction was a significant factor for bone and muscle (estimated α/β values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0–3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high α/β ration, inverse relationship with overall treatment duration, and faster development of mucosal complications suggests that they may develop as a consequence of earlier mucosal injury. As anticipated, adequate retrospective analysis of acute complications could not be amde even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalizations during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. Conclusions : The radiobiological characteristics of bone and muscle were those characteristics of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.