Thyroid cancer after radiotherapy for childhood cancer.

The thyroid gland in children is among the most sensitive organs to the carcinogenic effects of ionizing radiation, and very young children are at especially high risk. Risk associated with exposure to external X- or gamma-radiation increases linearly with increasing dose to the thyroid gland at low-to-moderate doses, but the dose-response relationship appears to flatten at the very high doses characteristic of cancer radiotherapy. Because of the extreme sensitivity of the thyroid gland in children, there is a risk of radiation-induced thyroid cancer even when the thyroid gland is outside of the irradiated field. Increased incidence of thyroid cancer has been noted following radiotherapy for childhood Hodgkin disease, non-Hodgkin lymphoma, neuroblastoma, Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system. Radiation-induced tumors begin to appear 5-10 years after irradiation and excess risk persists for decades, perhaps for the remainder of life. The background incidence of thyroid cancer is two- to threefold higher among females than males, and the absolute increase in risk due to irradiation is higher in females as well. Most of the thyroid cancers that occur in association with irradiation are of the papillary type, for which the cure rate is high if tumors are detected early. This highlights the importance of long-term surveillance of persons irradiated during childhood. Important areas for research include the possibility that children with certain types of first cancer are especially susceptible, the basis of the greater female susceptibility, the joint effects of radiation and other factors, and genetic mechanisms in radiation-induced and spontaneously occurring thyroid cancer.