Repair capacity and kinetics of human skin during fractionated radiotherapy: erythema, desquamation, and telangiectasia after 3 and 5 year's follow-up

Abstract

Prospective clinical fractionation studies on acute and late reactions in skin have been going on since 1972 at the Radiotherapy Department in Gothenburg. The clinical assay consisted of breast cancer patients irradiated postoperatively to the internal mammary nodes from unilateral or bilateral fields exposed to various dose schedules. 750 fields in 450 patients have been analysed. Schedules with 1, 2 or 5 fractions per week and 2 or 3 fractions per day were evaluated with erythema, desquamation and telangiectasia as endpoints. For some schedules a dose-response relationship was established in a limited dose range, but often there was only one dose group per schedule. These data are suited to analysis by the method of direct analysis of quantal response. This was used in the present analysis, along with the linear quadratic (LQ) model and its generalization, the incomplete repair (IR) model. The repair capacity was similar for erythema and desquamation, with alpha/beta ratios between 7.5 and 11.2 Gy. Unexpectedly, there was more significant time factor during radiotherapy courses up to 6 weeks for erythema and desquamation, but the repair capacity was changed after 4 weeks for both endpoints, and alpha/beta increased to between 18.3 and 34.5 Gy. The repair capacity for late telangiectasia differed significantly from that for erythema and desquamation, with alpha/beta values between 2.8 and 4.3 Gy. There was a significant time factor for telangiectasia with characteristic doubling time of about 16 days, when an exponential function for time was used. Concerning the repair kinetics in skin, there were insufficient data to obtain precise estimates, but there was a suggestion of two components of repair. This was inferred from higher-than-predicted recovery with 15-min intervals, when the data were fitted with the monoexponential model. The monoexponential fit gave t1/2 between 1.1 and 1.3 h for acute effects and 3.5 h for late effects. Recovery after 15-min fractionation intervals, if it resulted from a fast repair component, would be consistent with a half-time of 0.3-0.4 h. The time factor and the relative long half-time for repair for late effects have important implications for multiple-fraction-per-day treatment, and imply that interfraction intervals of 4 h or less, as commonly used, will be insufficient. Instead, intervals of 6 h or longer are recommended. Using accelerated fractionation with a significant reduction in overall treatment time a dose reduction is still necessary to take into account the time factor for late effects.(ABSTRACT TRUNCATED AT 400 WORDS)