this population, based on 84 deaths (ERR 0.08 Gy−1; 95% CI − 0.30, 0.65); this may result from the fact that the average dose the ovaries was high—5.5 Gy).

The risk of leukemia mortality in this cohort was studied further by Weiss and colleagues (1995), using a case-subcohort approach. A total of 60 leukemia deaths were observed during the follow-up period. Radiotherapy records were obtained for all but six of the deaths from leukemia excluding CLL, and individual doses to the red bone marrow were estimated as in the previous study; estimated doses were also available for the subcohort, as described in Weiss and colleagues (1994). The average dose to the total red bone marrow was estimated to be 4.44 Gy, but doses were nonuniform, with the heaviest dose to the lower spine. A linear-exponential model (in which the exponential term allows for cell sterilization in heavily exposed parts of the bone marrow), varying with time since exposure, provided a good description of the risk for non-CLL. The estimated ERR per Gy was 12.4 (95% CI 2.3, 52.1) 10 years after exposure; 1–25 years after exposure, the average ERR per Gy was estimated to be 7.0, based on 35 cases.

A Swedish cohort of 20,024 patients who received X-ray therapy between 1950 and 1964 for painful benign conditions of the locomotor system (including arthrosis and spondylosis) was followed for cancer incidence and mortality until the end of 1988 (Damber and others 1995). The average length of follow-up was 25 years. Average conversion factors between surface dose and mean absorbed dose in the red bone marrow were estimated by treatment site (for six sites), based on the treatment records of random samples of 30 subjects drawn from the cohort (Damber and others 1995). The conversion factors were applied to the entire cohort and used for stratification of subjects in different levels of exposure. The average absorbed dose to the red bone marrow was estimated to be 0.39 Gy. A total of 116 leukemia cases (115 deaths) were observed during the study period. The SIR and SMR for subjects with mean absorbed doses of 0.5 Gy or more were 1.40 (95% CI 1.00, 1.92) and 1.50 (95% CI 1.05, 2.04), respectively. No estimate of risk per unit dose was presented.

Thyroid Diseases

Iodine-131 is currently the treatment of choice for hyperthyroidism, largely because no serious side effects are known. Concerns remain, however, about the subsequent risk of cancer. Several studies of patients treated with 131I for hyperthyroidism have been carried out in the United States, Sweden, and the United Kingdom.

The occurrence of leukemia and of thyroid neoplasms (both benign and malignant) was studied among 36,050 patients treated for hyperthyroidism between 1946 and 1968 and included in the Cooperative Thyrotoxicosis Therapy Follow-up Study (Saenger and others 1968; Dobyns and others 1974). Approximately 20,000 subjects had been treated with 131I. The follow-up was active, with an average duration of 8 years. No excess of leukemia or thyroid cancer was observed among patients treated with 131I.

In a follow-up to this study, Hoffman (1984) studied cancer risk up to 1979 in the subgroup of 3696 women who had been treated at the Mayo Clinic, one of the original participating centers. Among these, 1005 had received 131I therapy alone and 2141 had been treated with surgery alone. A total of 527 cancer cases were identified in these two study groups; 175 were excluded because they occurred within a year of treatment. The mean observation period was 15 years for patients treated with 131I. The average whole-body dose is estimated to be of the order of 0.06–0.4 Gy in this cohort. There was no increased cancer risk among those treated with 131I and no indication of a relation with 131I activity delivered. Nonsignificant increased risks were seen for cancers in the two most exposed organs (thyroid and salivary glands, based on three and two cases, respectively).

Goldman and colleagues (1988) reported on an extended follow-up of 1762 women, included in the Cooperative Thyrotoxicosis Therapy Follow-up Study, who were treated at the Massachusetts General Hospital between 1946 and 1964. A total of 1406 had been treated with 131I. No dose estimation was conducted. The average follow-up duration was 17.2 years. An elevated SMR was noted in this cohort (SMR 1.3; 95% CI 1.2, 1.4) for all causes of death but not for all cancers (SMR 0.9; 95% CI 0.7, 1.1). A nonsignificantly increased SMR was noted for breast cancer (SMR 1.2; 95% CI 0.9, 1.5); no association with 131I activity was found.

Ron and colleagues (1998a) reported on mortality to the end of 1990 in the Cooperative Thyrotoxicosis Therapy Follow-up Study. The cohort included 35,593 hyperthyroid patients, 91% of whom had been diagnosed with Grave’s disease. Fewer than 500 subjects were less than 15 years of age at the time of treatment. The mean length of follow-up was 21 years, and 51% of the subjects had died during the study period. Doses from 131I to 17 organs (other than the thyroid) were estimated for each study subject by multiplying the amount of administered activity by the age-specific dose factor and 24-h thyroid uptake provided for each organ by the International Commission on Radiological Protection (ICRP 1988). Treatment with 131I was not related to all cancer mortality (SMR 1.02; 95% CI 0.98, 1.07) or to mortality from any specific cancer, with the exception of thyroid cancer (SMR 3.94; 95% CI 2.52, 5.86, based on 27 cases). A nonsignificant increase in mortality from thyroid cancer was seen with increasing 131I administered activity—when deaths occurring in the first 5 years after treatment were excluded, there was no evidence of a relationship with total activity; it is therefore likely that the underlying thyroid disease played a role in the observed cancer increase.

Cancer incidence was also studied in 4557 patients who received 131I therapy for hyperthyroidism in Sweden between 1950 and 1975 at Radiumhemmet, Sweden (Holm 1984). Information on thyroid disease and treatment was abstracted



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