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 fac tors on the development of late complications in mandibular bone, musc le, and mucosa of the oral cavity after external beam radiation therap y for carcinoma of the tonsil. Methods and Materials: A retrospective analysis was made of the results in 676 patients treated with a spectr um of fractionation regimens in nine centers during the years 1976-198 5. Only severe (Grades 3-4) late complications were analyzed. Results: With more than 5 years follow-up, it was found that total dose was a factor for all three types of complications, but that in other respect s, the radiobiology of late-(>3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Do se per fraction was a significant factor for bone and muscle (estimate d alpha/beta values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size o ver the range of approximately 1.0-3.5 Gy. Complications in bone and m uscle were not related to overall treatment duration, whereas there wa s a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bon e. The appearance of complications by 4 years after treatment was abou t 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high alpha beta ratio, inverse relationship wi th overall treatment duration, and faster development of mucosal compl ications suggests that they may develop as a consequence of earlier mu cosal injury. As anticipated, adequate retrospective analysis of acute complications could not be made even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalizat ion during treatment were the measures. Field size was a significant f actor for mandible complications, but not for muscle or mucosa. Conclu sion: The radiobiological characteristics of bone and muscle were thos e characteristic of other late-responding tissues, whereas late sequel ae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.