Variations with time and age in the risks of solid cancer incidence after radiation exposure in childhood.

The Japanese atomic bomb survivor incidence data set and data on five other groups exposed to ionizing radiation in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure. Overall, reductions of 5.7-6.1 per cent per year of time since exposure are indicated, depending on the time at which the reduction is presumed to start, and all the reductions are statistically significant at the 5 per cent level. There is no significant heterogeneity in the speed of the reductions in relative risk with time by cohort, by cancer type, sex, or age at exposure group. There is a significant reduction of relative risk with increasing age at exposure, but adjustment for age at exposure does not markedly affect the time trends of relative risk. For all of the groups considered, there is a statistically significant increase in the excess absolute risk with increasing time since exposure. However, by contrast with the relative homogeneity of the time trends of relative risk, there is statistically significant heterogeneity by cancer type within the Japanese cohort (P = 0.05) and between the cohorts (P < 0.0001) in the speed of increase of the excess absolute risk with time since exposure.

Benign thyroid adenomas among persons X-irradiated in infancy for enlarged thymus glands.

Thyroid adenoma incidence in a cohort of 2657 infants given X-ray treatment for a supposedly enlarged thymus gland, along with 4833 unirradiated siblings, has been ascertained for an average of 37 years since irradiation. Estimated thyroid doses ranged from 0.03 to > 8 Gy, with 62% receiving < 0.5 Gy. After excluding 4 adenoma cases with concurrent or previous thyroid cancer, there were 86 cases with pathologically diagnosed thyroid adenomas in the irradiated group and 11 in the sibling controls. The estimated excess relative risk (ERR) was 6.3 per gray (90% CI = 3.7, 11.2). Once the dose group with > or = 6 Gy, which was producing downward curvature in the dose-response function, was removed, the curve was compatible with linearity and the ERR was 7.8 per gray. Thyroid adenoma rates were elevated even at low doses: the lowest dose group (< 0.25 Gy) showed a significant elevation in risk. The relative risk appeared to be constant over time and was comparable for both sexes. Excess adenoma risk was observed in the irradiated group to the maximum follow-up interval of about 50 years. A number of potential risk factors for thyroid adenoma were examined both as risk factors in their own right and as modifiers of the radiogenic risk. Parity and use of hormones in relation to menopause were significantly associated with thyroid adenoma risk in women, while education, Jewish origin, history of hyperthyroidism or hypothyroidism, and family history of cancer were also adenoma risk factors in both sexes. An examination of interactions between possible risk factors and radiation suggested that women with a history of oral contraceptive use or hysterectomy and persons with a family history of cancer may have greater risk (per unit dose) of radiogenic thyroid adenomas than their counterparts.

Thyroid cancer among persons given X-ray treatment in infancy for an enlarged thymus gland.

A cohort of 2,657 infants in Rochester, New York, who were given x-ray treatment for a purported enlarged thymus gland, along with 4,833 siblings, have been followed by mail surveys through about 1986, which represents an average of 37 years of follow-up, to determine their incidence of thyroid cancer. Estimated thyroid doses ranged from 0.03 to > 10 Gy, with 62% receiving > 0.5 Gy. There were 37 pathologically diagnosed thyroid cancers in the irradiated group and five in the sibling controls. The dose-response relation was essentially linear, with no evidence of an additional dose-squared component. The estimated relative risk at 1 Gy was 10 (90% confidence interval 5-23). Thyroid cancer rates were elevated even at low doses; i.e., a dose-response analysis over the range of 0-0.3 Gy showed a significant positive slope. The risk ratio was declining over time but was still highly elevated to at least 45 years after irradiation. An examination of potential risk factors showed that older age at first childbirth was significantly associated with thyroid cancer risk. An evaluation of interactions between possible risk factors and radiation suggested that Jewish subjects and women with older ages at menarche or at first childbirth were at greater risk for radiogenic thyroid cancer.

Thyroid and thymic malignancy following childhood irradiation.

Synchronous thyroid and thymic malignancy following childhood thymic irradiation has only been reported in two known cases previously, with a third case identified here. A rationale is presented for following these radiated patients as they age with thyroglobulin and thyroid-stimulating hormone (TSH) levels as a measure of risk of the development of nodular thyroid disease and, if such occurs, for an aggressive surgical approach. There exists a growing population at risk attributable to the success of radiation treatment of Hodgkin's and pediatric head and neck tumors. The question is raised regarding the theoretical benefits of thyroid suppressive therapy in this group at risk. With the instructive case presented, radical surgery for either thymic or thyroid carcinoma and careful monitoring for decades-late local recurrences of thymoma are suggested.

Radiation-induced thyroid neoplasia.

Thyroid cancer is a well documented late effect of exposure to ionizing radiation. The excess risk begins 5-10 years after exposure and continues until at least 40 years after exposure. Females are roughly three times more susceptible to both radiogenic thyroid cancer and to thyroid cancer of other origins than are males. Therefore, relative risk estimates for radiogenic thyroid cancer do not necessarily differ by sex. The excess risk is higher among children exposed prior to five years of age than in those exposed later. The risk for radiogenic cancer following exposure to 131I appears to be lower than that following exposure to high dose-rate external irradiation, and in the Swedish diagnostic study 131I was nearly one fourth as efficient as external X-rays in inducing thyroid cancer. The Swedish data suggest that 131I is substantially less efficient in inducing thyroid cancer than high dose-rate exposures. In that study, however, 95% of the exposed individuals were 20 years or older (mean age 45 years).

Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations.

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

[Radiation-induced thyroid cancer]. / Cancers thyroïdiens radio-induits.

We describe thyroid carcinomas observed in two male patients after cervical irradiation in infancy. In the first case, irradiation was given for cervical angioma and in the second case, for enlarged thymus. A long time interval (16 and 43 years) elapsed between irradiation and the detection of the epitheliomas. The anatomopathological diagnosis was, for the first patient, papillo-vesicular epithelioma and for the second one, anaplastic carcinoma.

A comparative study between individuals receiving thymic irradiation in infancy and their nontreated siblings: clinical and laboratory thyroid abnormalities.

While impairment of thyroid function has been demonstrated for high-dose external radiation (e.g., for Hodgkin's disease), the long-term functional effects of low-dose external radiation have not been fully explored. One hundred fifty-three subjects with a past history of thymic irradiation during infancy were stratified into three dose levels and compared with 51 nonirradiated subjects from a sibling cohort with respect to previously undiagnosed clinical and laboratory thyroidal abnormalities. There was no apparent association between previous thymic irradiation and mean serum levels of T4, free T4, TSH, or antithyroid antibodies, nor was the prevalence of undetected hypothyroidism or hyperthyroidism significantly altered in the irradiated group. Serum thyroglobulin levels were elevated in subjects with palpable thyroid nodules, all of which occurred in thymic-irradiated subjects. Thus persons who have received low-level external thymic irradiation in infancy should continue to have periodic thyroid examinations, but routine serial measurement of other serum thyroidal parameters does not appear to be indicated.

Radiation and risk for thyroid cancer: atypical findings of a community thyroid recall program.

Screening of 553 persons for thyroid disease by scan and physical exam was performed. Group I (245) had documented irradiation, with most (85%) receiving 300 R for lymphoid hyperplasia. Group II (308) had only a history of prior irradiation. Abnormal glands were found in 17 of 245 (7%) of Group I with 7 of 245 (3%) having nodular disease. No cancers were found in six of eight (75%) persons with nodular disease having surgery. Abnormal glands were found in 45/308 (14.6%) of Group II with 16/308 (5.2%) having nodular disease. Twelve of 16 (75%) with nodular disease from Group II had surgery and three thyroid cancers were found; in addition, one person from this group had a history of prior surgery for thyroid cancer. The incidence of thyroid cancer in Group I was 0%, Group II was 1.3%, and the combined incidence was 0.7%. The relatively low incidence of thyroid cancer observed is attributed to the relatively late average age at time of irradiation; 22 years for Group 1, 13 years for Group II.

Thyroid and breast cancer following childhood radiation.

A 35-year-old man who received radiation for thymic enlargement as a child and subsequently developed both thyroid and breast cancer is reported. This appears to be the first case in which this association has been reported in a male.

Immunologic competence in adults following thymic irradiation in infancy.

Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

The relationship of head and neck irradiation to the subsequent development of thyroid neoplasms.

Individuals who have received head and neck radiation for benign conditions have a markedly increased risk of developing thyroid, salivary, and perhaps breast cancer as compared to the general population. Although the relative risk is very high, the absolute risk that any one individual who has had head or neck irradiation will develop a subsequent malignancy is low. Identification of these patients through some type of screening procedure may be beneficial in terms of prevention of subsequent morbidity and perhaps mortality from cancer, especially thyroid and salivary cancer. The risks of any detection or prophylaxis program must be carefully weighed against the probable, but unproved benefits of early detection. A major unresolved question is the natural history of microscopic thyroid carcinoma in the 25 yr-40 yr old radiation exposed population.

Late neoplastic changes following medical irradiation.

New additions since 1968 to the literature on radiation carcinogenesis in man support the earlier conclusion of an approximately linear increase in cancer incidence in a broad intermediate dose range for most sites of cancer. Questions are raised regarding the nature of the dose-response relation at very low and at very high dose exposures. Analyses of some data on exposure to radiation from internal deposits of radioactive material suggest that the dose-response curve at low and intermediate ranges in concave up, implying a smaller effect per unit exposure at very low doses than at intermediate ranges. Data on exposure to the very high but anatomically limited doses of radiation used in cancer therapy give conflicting results, suggesting in one report a continuation of the linear relation into the high-dose range. Other reports suggest a lesser effect per unit dose at high doses than at intermediate doses. Extensive laboratory studies of exposure of experimental animals indicate that over broad dose ranges, exceptions to simple linear relations are the rule, and that factors of dose rate and fractionation also affect the dose-response relation.