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, paraclinical 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 TGF beta 1 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.