The evaluation of low dose hyper-radiosensitivity in normal human skin

Abstract

Background and purpose The laboratory phenomenon of low dose hyper-radiosensitivity (LDHRS) describes an excess of cell kill at doses below 1 Gy relative to that predicted by the linear quadratic model. These data have stimulated clinical investigation into LDHRS in vivo. Patients and methods Skin was used as a model of normal human tissue. Two studies were initiated investigating the response to low doses of radiation. Study 1 compared once daily skin doses of ∼0.5 and >1.0 Gy in 24 patients receiving pelvic radiotherapy. Skin biopsies before and during radiotherapy were analysed histologically to assess the basal cell density (BCD). Study 2 compared two regimens of equal dose/time intensity—an ultrafractionated regimen (0.5 Gy TDS×12 days) with a conventional regimen (1.5 Gy OD×12 days). Skin biopsies taken during treatment assessed BCD and proliferative index. In both studies the changes in BCD were compared using non-linear regression analysis. Results Study 1. The results show a significantly greater reduction in BCD in the low dose group when BCD is plotted against dose. This effect is lost when BCD is plotted against time Study 2. The results demonstrate a significantly greater reduction in BCD in the higher dose/fraction arm. The proliferative response was similar in both treatment groups. Conclusions These data suggest that LDHRS does not occur in skin following doses of ∼0.5 Gy/fraction when regimens of equal dose/time intensity are compared. As only small volumes of normal tissue were irradiated it is difficult to predict the biological relevance of this with respect to larger field low dose per fraction irradiation regimens or risk of cancer induction. Equally we cannot extrapolate to effects resulting from exposure to doses <0.5 Gy or to the effects of low doses on other endpoints.