¹³¹I Ablation Treatment in Young Females After the Chernobyl Accident

Effective Half-Time of Iodide in Athyrotic Patients

To estimate the absorbed dose from ¹³¹I ablation treatment, one must know the effective half-time of ¹³¹I in athyrotic patients. The standard ¹³¹I dosimetric model of the International Commission on Radiological Protection assumes that inorganic iodine is rapidly excreted from blood, with a half-time of 0.25 d (10). However, after thyroidectomy, patients are told to discontinue thyroid hormone replacement and to consume an iodine-restricted diet for 3–6 wk before administration of radioactive iodine. This hypothyroid state substantially increases the half-time of inorganic iodine in the body, leading to a 2- to 3-fold increase in whole-body retention of radioiodine at 48 h (11–13). The increased biologic half-time of iodine in patients does not appear to be significantly influenced by uptake in thyroid remnants or metastases (13), because these tissues typically have a substantially reduced uptake and retention of ¹³¹I.

We identified 13 studies (Table 1) that estimated the mean effective half-time of ¹³¹I in athyrotic patients, with sample means ranging from 0.52 to 3.9 d. Most of these studies determined the effective half-time of ¹³¹I by fitting patient retention data with a single exponential function, thereby slightly underestimating the effective half-time. The data indicate that the effective half-time of iodide in athyrotic patients is log-normally distributed (14,15), with a mean ranging from 0.70 to 0.77 d.

A pooled analysis (sample-number weighted mean of the means) of the data in Table 1 gives a population mean effective whole-body half-time for ¹³¹I in athyrotic patients of 0.75 d. The pooled SD (PSD) from k series of measurements can be calculated aswhere n₁, n₂, …, n_k and s₁, s₂, …, s_k are the size and SD, respectively, of the individual studies. The pooled SD of the 10 studies that reported an SD is 0.37 d. Thus, the best estimate of the mean and SD of the effective whole-body half-time for ¹³¹I in athyrotic patients is 0.75 ± 0.37 d. If the analysis is restricted to the 10 studies with both a mean and an SD, the best estimate is 0.76 ± 0.37 d. The mean of the last study in Table 1 lies more than 2 SDs from either of these means (0.75 or 0.76 d) and thus may not belong to the same population. If this study is excluded from the analysis, the best estimate of the mean and SD of the effective whole-body half-time for ¹³¹I in athyrotic patients is 0.70 ± 0.28 d, very similar to that found in the studies of Pacilio et al. (14) and North et al. (15). In the present study, we used an effective half-time of 0.70 d in estimating dose from ¹³¹I ablation treatment in athyrotic pediatric and young adult patients.

¹³¹I Whole-Body and Breast Tissue Dosimetry

The OLINDA/EXM computer code (22) was used to estimate doses to various organs in 10-y-old, 15-y-old, and young adult females from ablation treatment. Uptake in stomach, liver, and intestines was assigned activity as in the standard model for iodide (23), and the remaining activity was assumed to be uniformly distributed throughout all tissues of the body and eliminated through the urinary pathway at a rate determined by the assumed whole-body effective half-time. The dynamic bladder feature of the code was used to estimate the number of disintegrations occurring in the urinary bladder. Table 2 provides estimates of breast, red marrow, and whole-body dose, assuming a total-body effective ¹³¹I half-time in athyrotic patients of 0.7 d and for the extreme mean half-times listed in Table 1 of 0.5 and 1.3 d. The best estimates of the dose to the breast in 10-y-old, 15-y-old, and young adult athyrotic females are 9.8E−2, 6.2E−2, and 6.2E−2 mGy/MBq, respectively (Table 2).

These calculations did not include the cross-dose contribution to breast tissue from ¹³¹I possibly taken up by thyroid remnants. Luster et al. (5) estimated the percentage of ¹³¹I uptake and the effective half-time in thyroid remnants for 14 lesions in 9 patients. The uptake varied from about 0.3% to 1.8% at 24 h (mean, about 0.5%), and the effective half-times varied from 1.25 to 5.4 d (mean, about 4.2 d) in hypothyroid adults. A sensitivity analysis using the OLINDA/EXM code indicated that cross dose from ¹³¹I in thyroid remnants may contribute from 6.6E−5 to 1.7E−3 mGy/MBq to the breast dose. Thus, if the data of Luster et al. (5) are representative, ¹³¹I taken up by thyroid remnants does not provide a significant cross dose to breast tissue.

Epidemiologic Studies

The major retrospective epidemiologic studies of women treated with ¹³¹I have not shown an increased rate of breast cancer in these women. If exposure to radioactive iodine can cause breast cancer, why have these studies not detected an increase in breast cancer rates? The most probable reason, aside from the fact that therapeutic doses of radioactive iodine may not cause breast cancer, may be that most women in these studies were over the age of 50 y at the time of exposure. Epidemiologic studies of exposure of the breast to external radiation indicate that the risk of radiation-induced breast cancer is minimal after the age of 45 y (26,28). The studies on atomic bomb survivors showed virtually no increased risk of breast cancer in women who were more than 40 y old at the time of exposure (29).

Three of the major studies on ¹³¹I-induced breast cancer were done by Hall et al. (2,3) and Franklyn et al. (4). The average age at treatment for patients in these 3 studies was 50, 57, and 57.1 y, respectively. The median latency period for breast cancer is about 20 y. Thus, breast cancer caused by ¹³¹I administered at the age of 50 y will generally not be detectable until the age of 70 y. At the age of 70 y, background breast cancer rates are high, making it difficult to detect small increases. In a pooled analysis of 8 cohorts, Preston et al. (26) estimated that after a 1.0-Gy exposure at the age of 25 y, the risk of breast cancer developing by the age of 65 y was 1.3 × 10⁻². In contrast, after a 1.0-Gy exposure at the age of 50 y, the risk of breast cancer developing by the age of 65 y was 4.8 × 10⁻⁸ and the risk by the age of 70 y was 5.2 × 10⁻⁸. About 6.3% (6.3 × 10⁻²) of women are between the ages of 50 and 70 y when breast cancer develops (30). Thus, it is unlikely that epidemiologic studies of women exposed to radioactive iodine after the age of 50 y will detect an increase in the incidence of breast cancer. These negative epidemiologic findings cannot be taken to demonstrate that ¹³¹I administered to younger women will not cause breast cancer.

Comparison with Data on Atomic Bomb Survivors

The data on atomic bomb survivors show that the female breast is the most radiation-sensitive tissue among the tissues in which solid cancer develops. In atomic bomb survivors, the average dose to breast tissue was 0.28 Sv, with an average age at exposure of 27 y (31). The excess relative risk for this cohort was 1.74 at 1 Sv. The excess relative risk of breast cancer in girls 5–14 y old at the time of exposure was 2.77 per Sv (31).

If we assume a median total applied dose of 10.7 GBq (289 Ci) of ¹³¹I for ablation treatment associated with Chernobyl (9), the dose to pediatric and young adult breast tissue from ¹³¹I ablation treatment ranges from 0.7 to 1.0 Gy. These doses to breast tissue are 2.5–3.5 times higher than the average dose to breast tissue in atomic bomb survivors. These doses are also higher than the median Chernobyl-related doses—estimated to range from 0.2 to 0.6 Gy—to thyroid tissue in children who developed thyroid cancer (32–34).