Total thyroidectomy followed by radioiodine therapy is an optimal treatment strategy that makes it possible to achieve a cure in a vast majority of pediatric patients with differentiated thyroid carcinomas. Risk of recurrence is strongly associated with tumor stage, extent of surgery, the young patient's age, and presence of symptoms at diagnosis.

DNA double-strand breaks (DSBs) are critical cellular lesions that can result from ionizing radiation exposure. A marker for DSB formation is the phosphorylated form of the histone H2 variant H2AX . DSBs also attract the damage sensor p53-binding protein 1 (53BP1) to the DSB-containing chromatin, because 53BP1 associates with the DSB-surrounding chromatin. We studied the induction, persistence, and disappearance of radiation-induced g-H2AX and 53BP1 foci after the first 131 I therapy of patients with differentiated thyroid carcinoma, a model for protracted, continuous, internal whole-body irradiation. Methods: Twenty-six patients (7 men, 19 women; mean age 6 SD, 42 6 13 y) underwent posttherapeutic blood dosimetry according to the standard operating procedure of the European Association of Nuclear Medicine, including peripheral blood sampling and external dose rate measurements at 2-144 h after administration of 131 I for thyroid remnant ablation. The mean time curves of dose accumulation and dose rate to the blood were compared with the mean g-H2AX and 53BP1 foci counts over the same period in samples of mononuclear peripheral blood leukocytes. Results: The mean absorbed dose to the blood in 24 patients evaluable for physical dosimetry was 0.31 6 0.10 Gy (minimum, 0.17 Gy; maximum, 0.57 Gy). After 24 h, the mean daily dose increment was less than 0.05 Gy. The excess focus counts per nucleus-that is, nuclear foci in excess of the low background count-peaked at 2 h after radioiodine administration (median excess foci for g-H2AX [n 5 21 patients], 0.227, and for 53BP1 [n 5 19 patients], 0.235) and progressively declined thereafter. Significantly elevated numbers of excess focus counts per nucleus (median excess foci for g-H2AX [n 5 8 patients], 0.054, and for 53BP1 [n 5 6 patients], 0.046) still were present at 120-144 h after therapy. Because the rate of occurrence of radiation-induced focus counts per nucleus per absorbed dose varied considerably among patients, a dose-response relationship could not be established for this series as a whole. The number of excess radiation-induced focus counts per nucleus per absorbed dose rate increased with time, potentially indicating a slower rate of DNA repair or, alternatively, a higher de novo rate of focus formation. The values over time of both radiation-induced DSB markers correlated closely (r 2 5 0.973). Conclusion: Radiation-induced g-H2AX and 53BP1 nuclear foci are useful markers for detecting radiation exposure after radionuclide incorporation, even for absorbed doses to the blood below 20 mGy. Exposure to ionizing radiation causes several lesions in affected cells because of direct ionization or radical attack (1). Among the most critical defects are DNA double-strand breaks (DSBs), which can lead to efficient cell killing or, through erroneous DNA repair, can be a source of stochastic damage, including increased risk of malignant transformation.Once a DSB forms, the cell initiates the DNA damage response, to which the ataxia-telangiectasia-mutated (ATM) protein,...

In spite of incomplete remission of thyroid cancer at cessation of RIT, a continuing spontaneous decline of TG and clinically stable partial remissions were observed in this collective of children. Therefore, if RIT does not show further effects, the administration of further courses should be handled restrictively.

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One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.

Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.

BACKGROUND Increased incidence of childhood thyroid carcinoma, particularly in the youngest children, has been reported from Belarus since the nuclear reactor accident at Chernobyl in 1986. The relation between disease severity and age at the time of the accident, not previously established in this cohort, was analyzed in this study. METHODS The authors studied the association between disease severity, expressed by TNM classification, and age at radiation exposure in a cohort of 483 patients younger than 8 years at the time of the Chernobyl accident who have been diagnosed with differentiated thyroid carcinoma since 1986 at the Center for Thyroid Cancer in Minsk. The associations between age at radiation exposure and TNM categories were compared among 4 groups of patients who were ages < 2, 2.1–4, 4.1–6, and 6.1–8 years at the time of the accident. Multivariate discriminant analysis was performed to examine the effects of age at the time of the accident, gender, histology, tumor stage, and N classification on the frequency of distant metastasis. RESULTS Younger age at the time of the Chernobyl accident was associated with greater extrathyroidal tumor extension (P < 0.01) and more lymph node involvement (P < 0.0001) and tended to be associated with more distant metastases (P = 0.09). Compared with patients who were ages 6.1–8 years at the time of the accident, patients who were younger than 2 years had significantly more extrathyroidal tumor invasion (P = 0.004), lymph node involvement (P = 0.004), and distant metastases (P = 0.05). The age at diagnosis increased with older age at the time of radiation exposure (linear regression analysis; correlation coefficient = 0.67; P < 0.001). Multivariate analysis revealed that younger age at the time of the accident (P = 0.001) and advanced locoregional tumor extension (P < 0.001) were the only powerful factors influencing the risk for distant metastasis of this malignancy. CONCLUSIONS The severity of disease was associated inversely with age at the time of radiation exposure in these cases of radiation‐induced childhood thyroid carcinoma. Cancer 2000;88:1470–6. © 2000 American Cancer Society.

In our initial patient cohort, high-activity (131)I therapy for advanced DTC based on pre-therapeutic blood dosimetry following the EANM SOP was safe and well tolerated. Such treatment almost always produced a partial biochemical tumour response.