Reversing the radiation-induced fibro-atrophic process.

Purpose. - The radiation-induced fibro-atrophic process described in numerous tissues and organs is a localized and irreversible late effect of high-dose radiation therapy. Our purpose is to show that this process is today reversible. Current knowledge and key points. - This review describes a synthesis of various clinical, para-clinical and histopathological aspects of radiation-induced fibro-atrophic process, and of cellular and molecular process regulation. Schematically, there exists a prefibrotic aspecific inflammatory phase, then a constituted and cellular phase, then a matricial densification and remodeling phase, associated in some cases with a tissular terminal necrosis. The respective parts and their evolution during time of the main protagonists as myofibroblast, extracellular matrix and growth factor TGFbeta1 are clarified. From the pathophysiological mechanisms described, curative therapeutic attitudes are proposed for the different progressive phases. Especially, superoxide dismutase (not available) and the pentoxifylline-tocopherol combination seem to allow reduction and reversibility of the fibro-atrophic radiation-induced established process, in clinics as in animal experiments. Future prospects and projects. - Some phase II trials try to assess the therapeutic interest of combined pentoxifylline-tocopherol in various radiation-induced sequelae, as in osteo-radionecrosis. A clinical randomized trial phase III has just been achieved and could support the results of these experimental and retrospective clinical trials. (C) 2002 Editions scientifiques et medicales Elsevier SAS.