Feasibility Study Shows Multicenter, Observational Case-Control Study Is Practicable to Determine Risk of Secondary Breast Cancer in Females With Differentiated Thyroid Carcinoma Given Radioiodine Therapy in Their Childhood or Adolescence; Findings Also Suggest Possible Fertility Impairment in Such Patients.

Objective: This single-center, observational case-control feasibility study sought to test key elements of a protocol for an eventual long-term international observational case-control study of a larger patient cohort, to evaluate the risk of breast cancer as a second primary malignancy in females with differentiated thyroid cancer (DTC) given radioiodine therapy (RAI) during childhood or adolescence. Patients: Females developing DTC after the Chernobyl accident in Belarus and ≤19 years old at the time of thyroid surgery were enrolled: patients given RAI (n = 111) and controls of similar age not given RAI (n = 90). Results: One case of breast cancer was newly diagnosed among the RAI patients, but none in controls. Patients given RAI significantly less frequently needed 2nd surgeries than did controls (23%, 26/111 vs. 39%, 35/90, P < 0.05); the main indication for such procedures usually is suspicion of local recurrence. RAI patients appeared to have had more frequent reproductive difficulties than did controls: 78% (87/111) of the former vs. 93% (84/90) of the latter had a history of pregnancy (P < 0.01), and the mean number of pregnancies was 1.5 ± 1.2 in RAI patients vs. 1.9±1.1 in controls (P < 0.05). Most notably, infertility was observed in 23% (26/111) of RAI patients vs. 4% (4/90) of controls (P < 0.01). In conclusion, a international observational case-control study on breast cancer after DTC in patients given RAI vs. not given RAI appears to be feasible. Additional research and everyday clinical attention should be devoted to reproductive function after RAI in young females.

Thyroid Cancer Induction: Nitrates as Independent Risk Factors or Risk Modulators after Radiation Exposure, with a Focus on the Chernobyl Accident.

In recent decades, differentiated thyroid cancer (DTC) incidence has been increasing worldwide. The important contributions to this phenomenon of "overdiagnosis" driven by wider use of improved ultrasound systems are amply documented, notwithstanding the "real" carcinogenic effects of ionizing radiation, e.g., from the Chernobyl accident or health care interventions. Less well understood is the role of nitrates - as environmental pollutants, in diet, and in medication - in thyroid carcinogenesis. Increasing exposure to nitrates is associated with rising incidence of esophageal, stomach, bladder, and colon cancers. Recent data suggest that in agricultural areas with higher mean nitrate levels in groundwater, DTC risk is also elevated. Our work in Belarus after Chernobyl has shown that children in districts with high nitrate concentrations in drinking water had significantly higher thyroid cancer incidence after irradiation than did their counterparts in areas with lower nitrate concentrations. Notwithstanding thyroid shielding, increasing use of computed tomography and dental X-rays heightens radiation exposure of the salivary glands in the general population, especially in children and adolescents. When nitrate intake is increased, salivary gland irradiation may potentially result in carcinogenic elevations in plasma nitric oxide concentrations. In conclusion, excess nitrate intake seems to be an independent risk factor for DTC. Additionally, we hypothesize from our data that high nitrate levels modulate the carcinogenic effect of radiation on the thyroid. Cohort studies, case-control studies, or both, are needed to quantify the effects of nitrates on DTC risk in the presence or absence of radiation exposure, e.g., that associated with diagnostic or therapeutic health care interventions.

Exercise-Induced Hypoxemia in Juvenile Thyroid Carcinoma With Lung Metastases.

PURPOSE: Exercise-induced arterial hypoxemia (EIAH) has been reported in patients with juvenile thyroid cancer treated with radioiodine for lung metastases. This retrospective study tested the hypothesis that EIAH is due to ventilation-perfusion-mismatch in this rare pulmonary condition. METHOD: 50 patients (age 13-23 years) treated for juvenile thyroid carcinoma and lung metastasis with 131I and 24 controls with thyroid cancer but without lung metastases and prior 131I-treatment were assessed in a state of acute hypothyroidism by com-puted tomography of the lungs, pulmonary function testing, cardiopulmonary exercise test with measurements of gas exchange, oxygen saturation, alveolar-arterial difference in pO2 (p(A-a)O2) and pCO2 (p(ET-a)CO2). RESULTS: 10 of the 50 patients with lung metastases showed EIAH. They had more pronounced pulmonary fibrosis on computed tomography, a widened p(A-a)O2, and p(ET-a)CO2, a lower DVE/DVCO2-slope, a lower respiratory rate and no increased dead space ventilation. A more pronounced EIAH was associated with male gender, younger age, lower diffusion capacity, higher p(ET-a)CO2 during exercise and a higher peak exercise tidal volume over vital capacity ratio. CONCLUSION: EIAH in patients with thyroid carcinoma and pulmonary metastases is not related to ventilation-perfusion mismatch but to alveolar hypoventilation, possibly related to an increased work of breathing with pulmonary fibrosis.

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

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.

Prognostic value of positron emission tomography-assessed tumor heterogeneity in patients with thyroid cancer undergoing treatment with radiopeptide therapy.

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) is a treatment option for both iodine-refractory differentiated and advanced medullary thyroid cancer (TC). It requires over-expression of somatostatin receptor subtype II (SSTR) that can be non-invasively assessed by positron emission tomography (PET). Assessment of tumor heterogeneity is increasingly used as a tool for prognostication prediction. We investigated the potential of SSTR-PET to assess intraindividual tumor heterogeneity and thereby treatment response prior to PRRT. METHODS: 12 patients with progressive radioiodine-refractory differentiated (1 papillary, 1 oxyphilic, 2 oncocytic, 4 follicular) or medullary (n=4) TC were enrolled. SSTR-PET was performed at baseline. Conventional PET parameters and heterogeneity parameters were analyzed regarding their potential to predict progression-free (PFS, mean, 221 days) and overall survival (OS, mean, 450 days). Parameters of a subgroup of lesions (n=23) were also correlated with morphological response according to modified RECIST criteria. RESULTS: In patient-based analysis, all conventional parameters failed to predict PFS. Several textural parameters showed a significant capability to assess PFS. Thereby, "Grey level non uniformity" had the highest area under the curve (AUC, 0.93) in Receiver operating characteristics analysis followed by "Contrast" (AUC, 0.89). In lesion-based analysis, only "Entropy" revealed potential to evaluate disease progression. OS could not be assessed by any parameter investigated. CONCLUSIONS: Tumor heterogeneity seems to be a predictor of response to PRRT in patients with iodine-refractory differentiated/advanced medullary thyroid cancer and outperforms conventional PET parameters like standardized uptake value. In a "theranostic" approach, assessment of textural parameters may help in selecting patients who might benefit from PRRT.

Bone mineral density in treated at a young age for differentiated thyroid cancer after Chernobyl female patients on TSH-suppressive therapy receiving or not Calcium-D3 supplementation.

Long-term management of patients with differentiated thyroid cancer (DTC) commonly includes TSH-suppressive therapy with L-T4 and, in case of postsurgical hypoparathyroidism, Calcium-D3 supplementation, both of which may affect skeletal health. Experience with female patients treated for DTC at a young age and who were then receiving long-term therapy with L-T4 and Calcium-D3 medication is very limited to date. This cross-sectional study set out to investigate effects of Calcium-D3 supplementation and TSH-suppressive therapy on bone mineral density (BMD) in 124 young female patients treated for DTC at a mean age of 14 years and followed-up for an average of 10 years. BMD was found to be significantly higher in patients receiving Calcium-D3 medication than in patients not taking supplements. The level of ionized calcium was the strongest factor determining lumbar spine BMD in patients not receiving Calcium-D3 supplementation. Pregnancy ending in childbirth and HDL-cholesterol were associated with a weak adverse effect on spine and femoral BMD. No evidence of adverse effects of L-T4 and of radioiodine therapies on BMD was found. We conclude that Calcium-D3 medication has a beneficial effect on BMD, and that TSH-suppressive therapy does not affect BMD in women treated for DTC at young age, at least after 10 years of follow-up.

Paralytic subileus as an adverse effect of amino acid-based nephroprotection in a patient undergoing peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy is routinely used for neuroendocrine tumors. To prevent radiopeptide retention at the proximal tubule of the kidney, positively charged amino are coinfused. However, hyperkalemia (>5.0 mmol/L) in more than three fourth of patients has been reported. In our case, the patient experienced acute hyperkalemia with blood values greater than 7.0 mmol/L with gastroparesis and subileus.

ß-Radiation exposure to fingertips after using a trained routine application method during radiosynovectomy.

There are few, but worrisome, data available on fingertip radiation exposure of medical personnel during radiosynovectomy (RSV). To reduce radiation exposure, we performed a dedicated application procedure. This report summarizes the acquired skin equivalent dose [Hp(0.07)] of the personnel involved in the preparation and administration of the three RSV ß-emitters Y, Re and Er. Over a period of 3 years, 547 joints in 368 patients were treated with 52421 MBq of the aforementioned three radionuclides. The Hp(0.07) was recorded with thermoluminescence dosimeters worn on the dominant index fingertip and was analysed monthly. Eight staff members were exposed to an Hp(0.07) of 492 mSv. The cumulative dose was less than 10 µSv/MBq. The dose per person was 1.1 µSv/MBq in physicians and up to 4.5 µSv/MBq in technicians. The accumulated personal Hp(0.07) during RSV was far below the regulatory limit and published data.

Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma.

CONTEXT: After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. DESIGN: We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. INTERVENTIONS: Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. MAIN OUTCOME MEASURES: Outcomes were response to therapy and disease status, mortality, and treatment toxicity. RESULTS: Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 µg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 µg/L), and 11 (4.8%) had partial remission (Tg > 10 µg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. CONCLUSIONS: 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.

Frequency of transferrin receptor positive reticulocytes (TF-Ret) in blood as an indicator of total-body radiation exposure: a pilot study in nuclear medicine patients.

Approximately 3-20% of all reticulocytes in blood of healthy persons are immature and transferrin receptor positive (Tf-Ret). Tf-Ret were measured by flow cytometry in 27 patients treated with three different radiopharmaceuticals labeled with (131)I and in 25 healthy controls. Patients were chronically exposed within 6 days to blood doses from 0.18-1.89 Gy (D6). Typically, two-thirds of D6 was administered within the first day (D1). The study had to be confined to intra-subject investigations due to high biological variability of Tf-Ret counts. A significant radiation-induced decline was found in patients D1 doses that were ≥0.5 Gy. Tf-Ret frequency declined during the first 4 to 5 days of nuclear therapy to about 30-60% of its initial value, and increased in the following 3 days without reaching the initial value. At the time of nadir, the relative frequency of Tf-Ret was more depressed than that of reticulocytes and lymphocytes. The relative Tf-Ret frequency at nadir could be fitted to the equation: %-Tf-Ret=exp-(D1/D(o)). D(o) was found to be 1.0 ± 0.4 Gy (Mean ± SEM). The study shows that Tf-Ret frequency in blood might be a good parameter for estimation of the radiation dose to red marrow.

Recombinant human thyrotropin to help confirm lack of evidence of radiation-induced differentiated thyroid cancer in young women seeking pregnancy.

BACKGROUND: Women with a history of differentiated thyroid carcinoma who are contemplating pregnancy may wish reassurance regarding apparent remission. However, the thyroid hormone withdrawal needed to obtain serum thyroglobulin testing (Tg) results in weeks-long biochemical and clinical hypothyroidism, which could increase miscarriage and fetal death rates if pregnancy occurred during withdrawal of thyroxine or soon thereafter. Recombinant human thyrotropin (rhTSH) elevates thyrotropin exogenously, allowing uninterrupted thyroid hormone therapy and avoids hypothyroidism. MATERIAL AND METHODS: Thirty female radiation-induced papillary thyroid carcinoma survivors who had undergone total- or near-total thyroidectomy and who were now seeking pregnancy (mean age 23.9 ± 1.8 years), and who were considered cancer-free by local standards, underwent rhTSH-aided Tg testing to help confirm remission. At the time of rhTSH testing, mean follow-up after primary surgical treatment was 11.1 ± 3.9 years, and all patients had negative neck ultrasonography, undetectable unstimulated serum Tg (< 0.2 ng/mL) and no interfering anti-Tg antibodies. However, based on T3, N1 or M1 status, 28/30 (93.3%) patients had high recurrence risk. RESULTS: rhTSH produced no serum Tg increase in 27/30 women (90.0%). Serum Tg increases to 0.4-0.9 ng/ml were observed in 3 women, but careful neck ultrasonography found no lymphadenopathy. Reassured about their remission, 14/30 women (46%) have become pregnant and delivered healthy children in the 3 years since rhTSH-aided testing. CONCLUSIONS: rhTSH-aided Tg testing is useful in confirming absence of tumor in female patients with a history of radiation-induced thyroid cancer who are seeking pregnancy, but who also have a high risk of thyroid cancer recurrence.

Pulmonary fibrosis in youth treated with radioiodine for juvenile thyroid cancer and lung metastases after Chernobyl.

PURPOSE: The objective of this project was to systematically determine the prevalence and consequences of pulmonary fibrosis in youth with thyroid carcinoma and lung metastases from Belarus who were treated with radioiodine ((131)I). METHODS: A total of 69 patients treated for juvenile thyroid carcinoma and lung metastasis with (131)I were assessed. A group of 29 patients without lung metastases and prior (131)I treatment served as controls. The assessments included a CT scan of the lungs, extensive pulmonary function testing and an incremental cycle test to volitional fatigue with measurements of oxygen uptake (VO(2)), oxygen saturation and alveolar-arterial difference in oxygen partial pressure (ΔaaO(2)). RESULTS: Five patients with lung metastases showed advanced pulmonary fibrosis on CT scans and also had poorer lung functions compared with the 62 patients with none or minor signs of fibrosis and the 29 controls. Furthermore, these five patients showed lower peak VO(2), lower oxygen saturation at peak exercise and higher exercise ΔaaO(2). They were younger at the time of cancer diagnosis and had received chemotherapy more frequently than youth with pulmonary metastases who did not develop fibrosis. One of the five patients subsequently died from pulmonary fibrosis. CONCLUSION: Following the Chernobyl catastrophe, about 7% of children treated with radioiodine for thyroid carcinoma and lung metastases displayed pulmonary fibrosis which was associated with functional impairments. Based on the characteristics of affected individuals, the number of radioiodine courses may have to be limited, especially in young children, and chemotherapy should be avoided.

I-131 activities as high as safely administrable (AHASA) for the treatment of children and adolescents with advanced differentiated thyroid cancer.

AIM: Differentiated thyroid carcinoma (DTC) in children and young adults is rare, can be aggressive, and often presents at advanced stages. In a population of young Belarusian patients with advanced DTC after the nuclear reactor accident at Chernobyl, we determined the activities that are as high as safely administrable (AHASA). PATIENTS AND METHODS: In 180 children and adolescents, we studied 133 courses of I-131 thyroid remnant ablation (median age at ablation, 14.3 yr) and 250 courses of I-131 therapy (median age at therapy, 15.7 yr). Remnant ablation was performed with weight-adapted I-131 activities of a median of 51.8 MBq/kg (range, 23.9-73.8 MBq/kg); and residual disease therapy was performed with a median activity of 98.0 MBq/kg (range, 56.7-164.7 MBq/kg). The radiation absorbed dose to the blood (BD) per unit of activity administered for each treatment was deduced from whole-body retention data measured twice daily using ceiling probes. The AHASA activity was calculated assuming an upper limit of 2 Gy BD. RESULTS: For I-131 ablation, the median weight-adjusted AHASA activity leading to a BD of 2 Gy was 407 MBq/kg (range, 137-661 MBq/kg). In three patients with extensive diffuse pulmonary metastases, the AHASA was lower than 200 MBq/kg. For patients receiving additional I-131 treatments after ablation, a median body weight-adapted AHASA activity of 406 MBq/kg (range, 210-775 MBq/kg) was calculated. CONCLUSION: Children and adolescents with advanced DTC can be treated with I-131 activities of at least 200 MBq/kg. For children with extensive pulmonary metastases, pretherapeutic dosimetry is needed to determine the AHASA.

Success of the postoperative 131I therapy in young Belarusian patients with differentiated thyroid cancer after Chernobyl depends on the radiation absorbed dose to the blood and the thyroglobulin level.

PURPOSE: Differentiated thyroid carcinoma (DTC) in children and young adults is rare but often aggressive and in an advanced stage at diagnosis. In a cohort of young Belarusian patients with advanced DTC after Chernobyl we retrospectively studied parameters influencing the success of the postoperative (131)I therapy. METHODS: Included in the study were 136 patients (83 female, 53 male; median age 14.3 years, range 9.4-22.8 years) who had had total thyroidectomy in Belarus and subsequent (131)I therapy and follow-up in Germany. Of the 136 patients, 34 were classified as M1 and 102 as M0 (N0 1, N1 101). The median weight-adjusted (131)I activity administered after thyroid hormone withdrawal was 52 MBq/kg (range 24-74 MBq/kg). TNM stage, gender, administered activity, whole-body residence time and blood dose during ablation, Tg and TSH levels, date, and age at time of treatment were tested for their effect on the rate of complete remission (CR). CR was defined as a negative scan and a stimulated Tg level of <1 ng/ml at follow-up. RESULTS: CR was observed in 1 of 34 M1 and in 51 of 102 M0 patients after the first treatment. Multivariate analysis in the M0 group identified the Tg level (P < 0.0001 for log(Tg)) and the radiation absorbed dose to the blood (P < 0.001) as independent determinants; all other parameters were unimportant (P > 0.3). The regression model was able to correctly predict CR in 82 of 102 patients (80.4%). CONCLUSION: In children and young adults with advanced DTC, the rate of CR after postoperative (131)I therapy is dependent on the preablative Tg level and the radiation absorbed dose to the blood. Though the present results must be confirmed in a prospective study, they imply that preablative dosimetry may improve rates of CR.

Favourable course of disease after incomplete remission on (131)I therapy in children with pulmonary metastases of papillary thyroid carcinoma: 10 years follow-up.

PURPOSE: The aim of this study is to report on a collective of 20 children from Belarus who had developed papillary thyroid carcinoma with pulmonary metastases after the Chernobyl disaster. In all children fractionated radioiodine therapy (RIT) was ceased before achieving complete remission due to a lack of further effects of (131)I therapy and an increased risk of pulmonary fibrosis. METHODS: The 20 children (12 girls) were treated with (131)I using 50 MBq/kg body weight for thyroid remnant ablation and 100 MBq/kg for further therapy in intervals of 5-12 months. After five to six courses and a cumulative activity of about 24 GBq (131)I no further RIT was conducted; the median thyroglobulin (TG) was 56 µg/l at this time. All patients were followed for at least 10 years after cessation of RIT using diagnostic whole-body scintigraphy, CT of the chest, lung function testing and stimulated TG measurements every 1-3 years. RESULTS: During follow-up after the last RIT a continuous decline of values for TG levels of ∼35% per year was observed between individual visits. The median Tg level at the time of cessation of (131)I therapy was 56 µg/l; however, at the last visit 16 of 20 patients had a TG level ≤10 µg/l (median 2.4 µg/l). Neither on diagnostic radioiodine whole-body scan nor on CT was progression of lung metastases observed. No significant pulmonary fibrosis developed. CONCLUSION: 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.

In vivo formation of gamma-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer.

UNLABELLED: 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 (gamma-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 gamma-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 +/- SD, 42 +/- 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 gamma-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 +/- 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 gamma-H2AX [n = 21 patients], 0.227, and for 53BP1 [n = 19 patients], 0.235) and progressively declined thereafter. Significantly elevated numbers of excess focus counts per nucleus (median excess foci for gamma-H2AX [n = 8 patients], 0.054, and for 53BP1 [n = 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) = 0.973). CONCLUSION: Radiation-induced gamma-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.

Dosimetry-guided high-activity (131)I therapy in patients with advanced differentiated thyroid carcinoma: initial experience.

PURPOSE: In patients with advanced differentiated thyroid carcinoma (DTC), therapy with the highest safe (131)I activity is desirable to maximize the tumour radiation dose yet avoid severe myelotoxicity. Recently, the European Association of Nuclear Medicine (EANM) published a standard operational procedure (SOP) for pre-therapeutic dosimetry in DTC patients incorporating a safety threshold of a 2 Gy absorbed dose to the blood as a surrogate for the red marrow. We sought to evaluate the safety and effectiveness in everyday tertiary referral centre practice of treating advanced DTC with high (131)I activities chosen primarily based on the results of dosimetry following this SOP. METHODS: We retrospectively assessed toxicity as well as biochemical and scintigraphic response in our first ten patients receiving such therapy for advanced DTC. RESULTS: The 10 patients received a total of 13 dosimetrically guided treatments with a median administered activity of 14.0 GBq (range: 7.0-21.4 GBq) (131)I. After 6 of 13 treatments in 6 of 10 patients, short-term side effects of (131)I therapy, namely nausea, vomiting or sialadenitis, were observed. Leukocyte and platelet counts dropped significantly in the weeks after (131)I treatment, but returned to pre-treatment levels by 3 months post-therapy. Serum thyroglobulin levels decreased after 12 of 13 treatments (median reduction: 58%) in 9 of 10 patients. CONCLUSION: 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.

The usual ultrasonographic features of thyroid cancer are less frequent in small tumors that develop after a long latent period after the Chernobyl radiation release accident.

BACKGROUND: The Chernobyl accident resulted in an unprecedented number of radiation-induced thyroid cancers in young individuals as detected by national and international screening programs. The vast majority of thyroid malignancies were papillary carcinomas that, despite being similar by histopathology, displayed large variability in clinical course. The correlations between ultrasound (US) and clinicopathological features in young patients with radiation-induced thyroid cancer, however, have not been well studied. Because of the importance of US for deciding which subjects should have fine-needle aspiration biopsy, we assessed the US features of papillary thyroid carcinoma in patients exposed to Chernobyl fallouts. DESIGN: We performed a retrospective multivariate logistic regression analysis of US features, clinicopathological data, and the latency period between radiation exposure and the diagnosis of cancer in 94 patients who were 10.6-34.3 years old (16.5 +/- 6.2, mean +/- standard deviation) at the time of diagnosis and 0.1-18.0 years old (5.6 +/- 4.2) at the time of the Chernobyl accident. RESULTS: Nodules greater than 10 mm were associated with the higher frequency of irregular margins (p = 0.001), longer period of latency (p = 0.016), and bilateral lymph node involvement (p = 0.025). Irregular tumor margins correlated with the shorter period of latency (p = 0.009) and unilateral nodal disease (p = 0.010). Hypoechoic nodules were observed more frequently in female patients (p = 0.012), in the absence of halo (p = 0.003) or calcifications (p = 0.005). Hypoechogenicity also correlated with the shorter latency (p = 0.015) and younger age of patients (p = 0.048). CONCLUSIONS: Irregular nodule margins, a usual sign of malignancy, are less useful in detecting thyroid cancers in radiation-exposed patients with tumors less than 10 mm. Thyroid cancers that are detected after longer latent periods display less of the US features characteristic of a malignant process, while benign US features are observed more frequently. Therefore, we recommend fine-needle aspiration biopsy to ensure early diagnosis of thyroid cancer for patients with a history of radiation exposure, even if their nodules are less than 10 mm.

Comprehensive clinical assessment of 740 cases of surgically treated thyroid cancer in children of Belarus.

OBJECTIVE: A retrospective study was designed to evaluate the results of surgical treatment and follow-up data in thyroid cancer patients less than 15 years old at the time of surgery. SUMMARY BACKGROUND DATA: Pediatric thyroid carcinomas have a high rate of lymph nodal and distant metastases. Risk factors for recurrences and postoperative morbidity have not been assessed yet in a representative series. METHODS: The group included 740 pediatric patients with thyroid cancer. Total thyroidectomy was performed in 426 (57.6%), lobectomy in 248 (33.5%), subtotal thyroidectomy in 58 (7.8%) cases, and 8 patients (1.1%) underwent partial lobectomy. RESULTS: The mean follow-up period was 115.8 months (range, 1.5-236.4 months). Recurrence was diagnosed in 204 cases (27.6%), including 73 local relapses (9.9%), 90 distant metastases (12.2%), and a combination of local and distant recurrences in 41 (5.5%) patients. Multivariate statistical assessment revealed the following independent parameters significantly associated with the risk of recurrent nodal disease: a young age at diagnosis, multifocal carcinomas, N1 status, and lack of neck lymph node dissection. For lung metastases, the significant risk factors were female gender, young age at diagnosis, and presence of symptoms. The observed 5- and 10-year survival for the entire group was 99.5% and 98.8%, respectively. Postoperative hypoparathyroidism was significantly associated with multifocal tumors, central compartment removal, and ipsilateral dissection. CONCLUSIONS: 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.