Radiotherapy by multiple fractions per day (MFD) in head and neck cancer: acute reactions of skin and mucosa.
The feasibility of several unusual fractionation schedules in the radiotherapy of head and neck tumors was assessed, especially the acute reactions of skin and mucosa. All schedules were based on the principle of multiple fractions per day (MFD) leading to highly concentrated treatment series, alternating with rest periods. The fraction sizes used were between 1.6-2 Gy, overall treatment time was about 6 weeks, and total dose ranged from 60 to 67.2 Gy. The most important parameter that was modified was the size of the dose given in one treatment series. The first schedule consisted of two unequal radiation series: 48 Gy/12 days, followed by a second series of 19.2 Gy/4 days after a 3- to 4-week interval. All subsequent treatment schedules were divided in equal series: the first in 2 times 30 Gy, the second in 3 times 22.4 Gy, and the third in 4 times 16 Gy. Comparison of acute reactions in skin and mucosa after these irradiations to different dose levels has made it possible to obtain a precise idea of the time course in the development of radiation induced damage and of the dose-effect relationship. Such dose-response curves will be extremely useful in further studies on the dose-modifying effects of sensitizers and cytostatic drugs. Conclusions of this study: 1. In human oral mucosa, the threshold dose for the development of confluent mucositis (patches of 0.5 cm) after fractionated irradiation appears to be around 20 Gy. 2. Intervals of 12 days allow full repair of mucosa damage after a dose of about 20 Gy and repeating the irradiation leads to an identical reaction after second, third or fourth treatments, demonstrating that no cumulative effect exists for acute damage. This phenomenon could be exploited to reduce the acute side effects in radiotherapy. 3. The reactions observed in skin are less pronounced than those of mucosa, possibly due to the dose distribution of high energy photons. The changes are, however, slower to develop and intervals of 2 weeks are insufficient for the skin to fully recover from the radiation damage. Subsequent treatment series led to a cumulative reaction pattern. 4. Finally, a number of treatments were associated with misonidazole, an anoxic cell sensitizer, which did not appear to modify significantly the radiation reactions in either skin or mucosa.
Department of Radiotherapy, Academisch Ziekenhuis St. Rafaël, Leuven, Belgium.
E
E
Van der Schueren
W
W
Van den Bogaert
L
L
Vanuytsel
E
E
Van Limbergen
D004307:Dose-Response Relationship, Radiation; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D009061:Mouth Mucosa / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D012867:Skin / Q000528:radiation effects*