High-dose-rate brachytherapy: Dose escalation in three-dimensional miniorgans of the human bronchial wall

Purpose: High-dose-rate (HDR) brachytherapy of human lung cancer is well es tablished, however fractionation schemes and dosages are based mainly on ex perience, The aim of this investigation was to study the effects of differe nt doses of HDR iridium-192 on normal human bronchial epithelium in three-d imensional miniorgans of the human bronchial wall. Methods and Materials: Forty-eight biopsies from normal bronchi were cultiv ated for 14 days and exposed at random to different doses of HDR iridium 19 2 (0 Gy, 30 Gy, 45 Gy, 60 Gy, or 75 Gy). Cell viability was assessed immedi ately after irradiation, after 4 or 18 days by fluorescent staining, and ce ll damage of the culture was analyzed by light microscopy, Lactate dehydrog enase (LDH) was measured in the supernatant for 4 days. Results: There was no histologically apparent tissue damage regardless of t he irradiation dose, The number of nonvital cells increased in irradiated m iniorgans depending on the dose used (p < 0.05 at 75 Gy), This effect occur -red early and was less pronounced with time, LDH measurements showed an in crease only in the first 24 hours. Conclusions: Our results confirm that normal bronchial epithelium has a hig h tolerance to early epithelial damage by irradiation. This model of human bronchial miniorgans is useful for further studies of the effects of irradi ation on human bronchi, (C) 2000 Elsevier Science Inc.