Radiation-induced fibrosis (RIF) is a chronic, progressive disorder resulting from exposure to ionizing (α, β, γ) radiation. It is considered a late effect of ionizing radiation, typically appearing within 3 months after completion of radiation and progressing slowly for up to years thereafter. RIF is most commonly seen after radiation for solid tumor malignancies, such as for breast (female, male), head and neck, lung, prostate, and gynecologic cancers.

The risk and extent of RIF depend on multiple factors, including the radiation site, total dose, dose per fraction, area of tissue treated, sensitivity of tissue exposed, and duration of treatment. Older age at the time of radiation therapy may also increase susceptibility to RIF due to reduced tissue repair capacity. Certain patient-specific factors can also increase vulnerability to RIF, such as having a connective tissue disease (eg, systemic sclerosis, lupus, Marfan syndrome), diabetes mellitus, and a history of surgery or trauma in the irradiated area. Additional risks are associated with concurrent chemotherapy (particularly with agents such as bleomycin or doxorubicin) and genetic predispositions that affect DNA repair mechanisms such as ataxia-telangiectasia, Fanconi anemia, Bloom syndrome, and xeroderma pigmentosum.

Radiation induces oxidative stress, endothelial damage, and chronic inflammation, leading to the upregulation of fibrogenic cytokines, especially transforming growth factor-beta 1 (TGF- β1). As a result, fibroblasts transform into myofibroblasts, there is excess collagen and extracellular matrix (ECM) deposition, and simultaneously, decreased matrix metalloproteinase (MMP) activity. This results in thickening and stiffening of tissue, hypovascularity, and loss of normal architecture, resulting in deformity, functional impairment, and pain over time.

The skin, subcutaneous tissue, muscle, fascia, and internal organs in the radiation field can all be affected. In the skin, RIF may be accompanied by other chronic radiation changes, such as epidermal atrophy, dyspigmentation, and telangiectasias (chronic radiation dermatitis).

Radiation for head and neck malignancy can result in trismus due to fibrotic changes affecting the muscles of mastication; neck instability, head drop, and torticollis due to fibrosis; atrophy; contractures of the sternocleidomastoid and scalene muscles; and dysphagia and aspiration due to fibrosis of pharyngeal constrictor muscles.

Radiation for breast cancer may cause fibrosis of lymphatics and soft tissues that may lead to lymphedema, along with causing skin / subcutaneous fibrosis, that may result in functional impairment of the breast and shoulder.

Cardiovascular disease may occur, even from low-dose radiation to the thorax, mediastinum, or neck, secondary to clinically significant pericardial fibrosis, myocardial fibrosis that may lead to conduction abnormalities, valvular fibrosis, and coronary vasculopathy.

Radiation for abdominopelvic malignancies can result in intestinal fibrosis, manifesting as malabsorption, motility changes, strictures, fistulae, bleeding, obstruction, or perforation. Other features include mesenteric and bowel wall thickening with altered peristalsis and small bowel fixation; genitourinary sequalae including cystitis, hematuria, incontinence, and strictures; gynecologic complications such as vaginal stenosis with dryness, atrophy, and loss of elasticity; and widespread radiation fibrosis across organs leading to reduced tissue compliance and organ-specific functional impairment.