Neoplasms in Children Treated With X Rays for Thymic Enlargement. II. Tumor Incidence as a Function of Radiation Factors

The tumor incidence in 2,809 children treated with X rays for thymic enlargement was analyzed in terms of the dose and other radiation factors. Because of the small number of specific types of neoplasms, the tumors were combined for analysis into three categories: 1) all thyroid tumors, 2) other tumors inside the directly treated tissues, and 3) tumors outside the directly treated tissues. A striking increase of all neoplasms, less marked for tumors outside the treated tissues, was noted as the children grew older. This complicated the analysis because the older children usually received higher doses through larger ports, frequently placed posteriorly as well as anteriorly. When the age relationship was corrected by the use of cohort-analysis, a given air dose administered half anteriorly and half posteriorly to the chest was associated with a significantly higher tumor incidence than that observed when the same total dose was given only anteriorly. The incidence of thyroid tumors was considerably higher with the former technique. Irradiation both anteriorly and posteriorly was also associated with a strong tendency of the tumors to cluster in primary irradiated tissues, a phenomenon not as pronounced when anterior irradiation alone was used. Attempts to demonstrate a dose dependence for the major treatment groups, i.e., combined anterior and posterior, and anterior treatments were unsuccessful. The failure to show a dose response was attributed to the small number of neoplasms, rather than to definite evidence of an absence of such an effect. The clustering of tumors in the directly irradiated tissues and the apparent effect of port arrangement on tumor incidence constitute strong circumstantial evidence favoring radiation exposure as an etiologic factor in tumor production. The apparent effectiveness of combined anterior and posterior irradiation in inducing tumors could be due to exposure of certain tissues in the head and neck with this port arrangement. These tissues, including the pituitary gland, were not likely to be exposed when anterior ports alone were used. Possibly the 2-week interval between treatments of the group of children with the highest tumor incidence also augmented the oncogenic action of the radiation exposure.