Identification and Management of Radiation Late Effects in Humans

Information on radiation late effects has come principally from experiences in the follow-up of clinical radiotherapy patients. Over the last 100 years, radiation has been used therapeutically to treat cancer and the numbers of long-term survivors have increased. Cancer survivors provide valuable information on the long-term effects of radiation. The most robust information comes primarily from those long-term survivors of radiotherapy for head and neck cancer and gynecologic cancers. A common late effect appears to be associated with fibrosis or scar formation. The molecular mechanism of this radiation late effect is a subject of intense investigation. With respect to specific organ and whole-body radiation late effects, experiments with mice and nonhuman primates have revealed significant concern for late carcinogenesis and organ failure. Those late effects are also seen in humans. Irradiation induces accelerated aging in part associated with consumption of antioxidants and amplification of fibrosis pathways. The information on late effects has provided clinicians with the ability to detect the trajectory of the initiation of late effects and direct application of new drugs to decrease late effects. There are new strategies for developing ways to ameliorate the deleterious effects of radiation in cancer survivors. The information from clinical radiotherapy will be valuable for managing radiation side effects in astronauts, as well as in the survivors of nuclear reactor accidents and nuclear bomb detonations.