Radiation fibrosis--current clinical and therapeutic perspectives.

Cancer survivors previously treated with curative radiotherapy are at risk of developing long-term toxicities due to radiation-induced normal tissue injury. Radiation fibrosis is an important component of the spectrum of radiation injury and at the present time treatment for this condition is limited. Data from both studies of clinical intervention and from preclinical models support the idea that fibrosis is a dynamic process and may in part be reversible. Clinical therapeutic interventions for radiation fibrosis have included empirical treatments, such as antioxidant therapies using superoxide dismutase, or vitamin E and pentoxifylline, and although evidence for therapeutic efficacy exists, further randomised studies are required. Potential therapeutic strategies that have shown promise in preclinical models include targeting pro-fibrotic cytokines such as: (1) transforming growth factor beta 1, (2) platelet-derived growth factor and its receptor tyrosine kinase and (3) connective tissue growth factor and the Rho/ROCK intracellular signalling pathway. Progress in the understanding of stem cell biology and the involvement of stem cells in radiation injury has led to the investigation of their role as a therapeutic strategy for ameliorating this disease process by promoting organ regeneration and repair. In this review we discuss the clinical and pathological features of radiation fibrosis and present the available clinical data and laboratory data relevant to these approaches to therapeutic intervention.

Hypoxia can be detected in irradiated normal human tissue: a study using the hypoxic marker pimonidazole hydrochloride.

Chronic tissue hypoxia may play a role in the pathogenesis of late radiation fibrosis. In order to investigate this hypothesis, the immunohistochemical distribution of pimonidazole hydrochloride (n = 14 patients) and carbonic anhydrase IX (CAIX) (n = 38 patients) was studied in samples of previously irradiated normal human tissue. One sample of irradiated breast tissue, which also showed marked histological features of radiation injury, stained positive for pimonidazole hydrochloride. No CAIX staining was seen in irradiated tissue other than some evidence of physiological hypoxia in the epidermis of two samples of irradiated skin; both were positive for pimonidazole and one was focally positive for CAIX. Pimonidazole hydrochloride staining of tissue with morphological changes of radiation injury could support a role for hypoxia in the pathogenesis of late normal tissue fibrosis in humans.

Raynaud's phenomenon after radical radiotherapy for tumours of the head and neck.

Endothelial cell injury is implicated in the development of radiation induced tissue damage and may also be involved in the pathophysiology of secondary Raynaud's phenomenon. Two patients are presented in whom the typical symptoms and signs of Raynaud's phenomenon developed as a late complication of radical radiotherapy. One had Raynaud's of the tongue and one of the lip. Both patients had a prior history of primary Raynaud's phenomenon and in each case the symptoms were repeatedly precipitated by sudden cold exposure. The possible pathogenesis of radiation induced Raynaud's phenomenon in the head and neck region is discussed.