W: Late radiation-related fibrosis: pathogenesis, manifestations, and current management. Semin Radiat Oncol 2003

Radiation-induced fibrosis (RIF) represents one of the most common long-term adverse effects of curative radiotherapy. Current cancer treatment approaches, in-volving more intensive radiotherapy regimens, used in combination with systemic agents, will likely be asso-ciated with a higher incidence and greater degree of damage to normal tissues, especially RIF. Traditionally, the development of fibrosis after radiation therapy has been considered static and irreversible. Contemporary understanding recognizes RIF as a continuum of re-sponses mediated by molecular pathways that may be amenable to interventions. Preliminary evidence sug-gests that pharmacological or other interventions may be possible to reverse the manifestation of the injury and restore function to tissues. A variety of strategies have been tested for the management of RIF, although formal trials of these therapies that permit treatment comparisons are unavailable at this time. It is critical that we formally evaluate new management ap-proaches for RIF with larger patient accrual. To this end, it is also important to develop a means of registering its occurrence for outcome analysis and to refer these pa-tients to colleagues familiar with optimal management and enrollment in clinical trials. © 2003 Elsevier Inc. All rights reserved. The influence of radiation-induced fibrosis(RIF) depends on the anatomic site and may range from solely subjective to very objective manifestations. In this article, the proposed un-derlying mechanisms of fibrosis are briefly re-viewed as well as current management options. We discuss the biologic rationale of currently available interventions and explore potential ar-eas of study for the future. One focus that will be emphasized is the dynamic nature of RIF repre-senting a continuum mediated by molecular pathways that may be amenable to modulation