Radiation-induced fibrosis can develop as a late effect of radiation therapy (RT) in skin and subcutaneous tissue, lungs, the gastrointestinal and genitourinary tracts, muscles, or other organs, depending upon the treatment site. Radiation-induced fibrosis may cause both cosmetic and functional impairment, which can lead to death or a significant deterioration in the quality of life.
The development of radiation-induced fibrosis is influenced by multiple factors, including the radiation dose and volume, fractionation schedule, previous or concurrent treatments, genetic susceptibility, and comorbidities such as diabetes mellitus. Although radiation-induced fibrosis originally was assumed to be a slow, irreversible process, contemporary studies suggest that it is not necessarily a fixed process.
The prevention of radiation-induced fibrosis has focused on improvements in RT technique, which have resulted in higher doses to the tumor target and decreased doses to normal tissue, thus potentially preventing the development of radiation-induced fibrosis. Furthermore, established radiation-induced fibrosis may be treatable with novel therapeutic approaches, particularly the combination of pentoxifylline and vitamin E.
The pathogenesis, diagnosis, clinical manifestations, prevention, and treatment of radiation-induced fibrosis will be discussed here. Radiation-induced changes in the lungs and gastrointestinal tract are discussed separately. (See "Radiation-induced lung injury" and "Diagnosis and management of chronic radiation enteritis".)
Radiation-induced fibrosis is similar to inflammation, wound healing, and fibrosis of any origin. Typical histologic features include the presence of inflammatory infiltrates, particularly macrophages in the earlier stages of fibrosis, differentiation of fibroblasts into postmitotic fibrocytes, and changes in the vascular connective tissue with excessive production and deposition of extracellular matrix proteins and collagen [1,2].