Publications by authors named "Claire Schvartz"

33 Publications

Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium.

Int J Cancer 2021 Feb 2. Epub 2021 Feb 2.

University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Team "Epidemiology of radiations", Villejuif, France.

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. DTC is one of the cancers with the highest familial risk suggesting a major role of genetic risk factors, but only few susceptibility loci were identified so far. In order to assess the contribution of known DTC susceptibility loci and to identify new ones, we conducted a multiethnic genome-wide association study (GWAS) in individuals of European ancestry and of Oceanian ancestry from Pacific Islands. Our study included 1554 cases/1973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from seven population-based case-control studies participating to the EPITHYR consortium. All participants were genotyped using the OncoArray-500K Beadchip (Illumina). We confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 and 16q23.2, which were associated with thyroid-stimulating hormone levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. We also observed that the frequencies of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans. However, additional GWAS and epidemiological studies in Oceanian populations are needed to fully understand the highest incidence observed in these populations.
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http://dx.doi.org/10.1002/ijc.33488DOI Listing
February 2021

Progression of incidence and estimate of net survival from papillary thyroid cancers diagnosed between 2008 and 2016 in France.

Ann Endocrinol (Paris) 2020 Dec 5;81(6):530-538. Epub 2020 Dec 5.

FRANCIM, 1, avenue Irène-Joliot-Curie, 31059 Toulouse, France.

Background: After several decades of increasing incidence of papillary thyroid cancer (PTC), a change in this trend has been recently observed, particularly in the United States. This is attributed to the impact of new guidelines for the management of thyroid disease. The objective of this study was to describe the recent situation in France in terms of incidence and survival, taking account of tumor size.

Methods: Data from the FRANCIM network cancer registries, covering around 25% of the French metropolitan population, were analyzed. Distribution according to tumor size was determined in terms of frequency, trends in incidence and spatial distribution for the period 2008-2016. Analysis of net survival considered gender, age and tumor size.

Results: Cancers of size≤5mm were predominant in patients diagnosed between 55 and 74 years of age. Incidence of≤5mm tumors in women and of 5-10mm tumors in men began declining in the early 2010s. Incidence of 10-20mm and 20-40mm tumors in men increased significantly throughout the period 2008-2016. For both men and women, the incidence of the largest tumors (>40mm) also increased, but not significantly. The spatial distribution of incidence showed great heterogeneity. Net survival was generally high, although decreasing with age and tumor size.

Conclusion: The recent epidemiological situation in France is consistent with the hypothesis of recent progress in medical management of thyroid pathologies. Variations in incidence should be monitored for both small (<10mm) and larger tumors, and notably>40mm tumors. Net survival is generally high, although decreasing with age and tumor size.
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http://dx.doi.org/10.1016/j.ando.2020.11.006DOI Listing
December 2020

Long-term progression of non-invasive follicular thyroid neoplasm with papillary-like nuclear features: A single-center retrospective study of the French Marne-Ardennes thyroid cancer registry.

Ann Endocrinol (Paris) 2020 Feb 25;81(1):34-38. Epub 2020 Jan 25.

Nuclear medicine-thyroid Unit, Institut Godinot, 1, rue du Général-Koenig, 51100 Reims, France; Thyroid Cancer Registry of Marne-Ardennes, Institut Godinot, 1, rue du Général-Koenig, 51100 Reims, France.

Context: Non-invasive forms of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) were reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in order to reduce overtreatment. A few studies showed neck lymphadenopathy at diagnosis, or even distant metastasis in patients with NIFTP.

Objective: Our aim was to report the frequency, clinical features and long-term progression of histologically confirmed NIFTP, using data from the French Marne-Ardennes thyroid cancer registry, and to compare findings against FVPTC.

Methods: This was a retrospective study on data for follicular variant of PTC (FVPTC) diagnosed between 1975 and 2015 obtained from the specialized Marne-Ardennes thyroid cancer registry. Pathology reports were used to select appropriate cases from a large series, and FVPTC specimens were reviewed by endocrine pathologists. Strict diagnostic criteria were used for reclassification as NIFTP.

Results: In total, 115 cases were reviewed histologically out of 383 cases of FVPTC. Sixty-five met all criteria for NIFTP and were consequently reclassified. Incidence of NIFTP was 16.9% of cases of FVPTC. Fifty patients were women (76.9%); median age was 47 years. Mean NIFTP size was 2.6 cm. There were no significant differences in age, gender or tumor size between NIFTP and FVPTC. Fifty patients underwent total thyroidectomy and 15 lobectomy. There were no lymph node metastases at diagnosis, and none of the patients (N=17) who underwent central and/or lateral neck dissection had positive findings on microscopic examination. 46 patients (70.8%) received radioiodine (RAI). Patients were followed up for 1.9-27.3 years (median 14.6 years) after initial treatment. All patients remained in complete remission during follow-up.

Conclusion: Consistently with previous studies, our results showed the indolent course of NIFTP and that risk of recurrence after complete resection is very low (zero in our cohort), even when size is ≥4cm and in absence of adjuvant RAI treatment. Prospective studies are needed to confirm those results.
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http://dx.doi.org/10.1016/j.ando.2019.12.001DOI Listing
February 2020

Role of GSTM1 and GSTT1 genotypes in differentiated thyroid cancer and interaction with lifestyle factors: Results from case-control studies in France and New Caledonia.

PLoS One 2020 30;15(1):e0228187. Epub 2020 Jan 30.

Université Paris-Saclay, UVSQ, INSERM, CESP, Villejuif, France.

Background: GSTM1 and GSTT1 are involved in detoxification of xenobiotics, products of oxidative stress and in steroid hormones metabolism. We investigated whether GSTM1 and GSTT1 gene deletion was associated with DTC risk and explored interaction with non-genetic risk factors of DTC.

Methods: The study included 661 DTC cases and 736 controls from two case-control studies conducted in France and New Caledonia. Odds ratios (OR) and their confidence interval (CI) for DTC associated with GST genotypes, alcohol drinking, tobacco smoking, body mass index and hormonal factors were calculated using logistic regression models.

Results: Results are presented for Europeans and Melanesians combined, as no heterogeneity between groups was detected. We found that DTC risk increased with obesity and decrease with alcohol drinking. After stratification by gene deletion status, the OR for obesity was 5.75, (95%CI 2.25-14.7) among individuals with GSTT1 and GSTM1-deleted genotype, and 1.26, (95%CI 0.89-1.77) in carriers of both genes (p-interaction = 0.02). The OR for drinking ≥1 glass/week was 0.33 (95%CI 0.15-0.74) in GSTT1-null individuals while it was 1.01 (95%CI 0.67-1.52) in non-null carriers of the gene (p-interaction = 0.01). No interaction between GST genotypes and other non-genetic risk factors was detected.

Conclusion: GSTM1 and GSTT1 genotypes may modulate the DTC risk associated with BMI and alcohol consumption.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228187PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992216PMC
May 2020

Micropapillary carcinoma: Description and rise in incidence in the French Marne-Ardennes thyroid cancer registry.

Ann Endocrinol (Paris) 2019 Sep 8;80(4):229-233. Epub 2019 Jul 8.

Thyroid Cancer Registry of Marne-Ardennes, Institut Jean-Godinot, 1, rue du Général-Koenig, 51100 Reims, France.

Context: Yearly incidence of thyroid cancer has nearly tripled in the past four decades, due to improvements in and better use of diagnostic procedures, enabling detection of smaller tumors, and notably micropapillary carcinoma (MPC: ≤10 mm).

Objectives: The aim of our study was to confirm increasing incidence, to describe the characteristics and circumstances of discovery, and to examine the reasons for this rise in incidence of MPCs, based on the French Marne-Ardennes registry for 1975-2014.

Design: This was a retrospective observational cohort study.

Results: Two thousand six hundred and seventy-one patients with thyroid cancer were included for the period 1975-2014, with 966 (36.2%) MPCs. The percentage increased from 18.9% for 1975-1984 to 45.1% for 2005-2014. Standardized incidence per 100,000 patient-years increased from 0.86 for 1975-1984 to 6.20 for 2005-2014. Incidence increase was higher in women (ranging from 1.15 to 8.91) than in men (from 0.20 to 2.54). Incidence increased more in ≥50 year-olds (from 0.41 to 4.21) than in <50 year-olds (from 0.45 to 1.99). Most MPCs (84.6%) were discovered incidentally on histology, and were mainly unifocal (79.4%). Incidental MPCs were smaller, affected older patients and were less multifocal than those suspected before surgery. MPCs were associated with excellent survival and low morbidity, with <1.9% progression.

Conclusion: The present study confirmed the large rise in incidence of MPCs reported elsewhere. Most MPCs were discovered incidentally on histological examination in the context of surgery for benign pathology. Changes in access to health care and in physicians' and pathologists' practices are likely explanations for our findings.
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http://dx.doi.org/10.1016/j.ando.2019.06.001DOI Listing
September 2019

Three Consecutive Pregnancies in a Patient with Chronic Autoimmune Thyroid Disease Associated with Hypothyroidism and Extremely High Levels of Anti-Thyrotropin Receptor Antibodies.

Thyroid 2019 05;29(5):743-747

1 Service d'Endocrinologie - Diabète - Nutrition Reims, Centre Hospitalier Universitaire de Reims, Champagne-Ardenne, France.

Thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAb) can be present in chronic autoimmune thyroiditis. Transplacental TRAb transfer can lead to fetal thyroid dysfunction and serious complications. We report the case of a woman with autoimmune hypothyroidism and extremely high TRAb levels, with blocking and stimulating activities (biological activities characterized with Chinese hamster ovary cells expressing TSHR). At week 22 of her first pregnancy, sonography detected fetal growth retardation and cardiac abnormalities (extreme tachycardia, right ventricular dilatation, pericardial effusion). The mother's TRAb level, assayed later, was 4030 IU/L ( < 10). Delivered via caesarean section gestational week 30, the newborn girl had several malformations, signs of malnutrition, goiter and hyperthyroidism associated with elevated TRAb (1200 IU/L). The newborn died 26 days after delivery. Faced with persistently high TRAb levels and a desire to become pregnant again, the woman was treated with three consecutive 740-MBq activities of iodine-131, which resulted in a decrease in TRAb to 640 IU/L. The patient had two subsequent pregnancies 16 and 72 months after the radioiodine administration. During the close follow-ups, fetal development was normal, and initial TRAb levels during the two pregnancies were 680 and 260 IU/L, respectively, which initially decreased but then increased in late pregnancy. In both cases, labor was induced at 34 weeks. The newborns, mildly hyperthyroid at birth, required carbimazole treatment at days 5 and 2, respectively. The mild hyperthyroidism despite high TRAb levels was likely due to the concomitant presence of stimulating and blocking TRAb. The two girls, now aged 12 and 8 years, are in good health. The mother has no detectable thyroid gland tissue and is euthyroid on levothyroxine (175 μg/d). Her TRAb level gradually decreased to 136 IU/L. This remarkable case illustrates the severe consequences of untreated fetal hyperthyroidism and the need to assay and follow-up TRAb levels in women of reproductive age with autoimmune thyroiditis.
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http://dx.doi.org/10.1089/thy.2018.0098DOI Listing
May 2019

Recombinant Thyrotropin vs Levothyroxine Withdrawal in 131I Therapy of N1 Thyroid Cancer: A Large Matched Cohort Study (ThyrNod).

J Clin Endocrinol Metab 2019 04;104(4):1020-1028

Aix-Marseille University, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille, France.

Context: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC).

Objectives: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC.

Design: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3).

Results: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors.

Conclusions: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.
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http://dx.doi.org/10.1210/jc.2018-01589DOI Listing
April 2019

Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial.

Lancet Diabetes Endocrinol 2018 08 26;6(8):618-626. Epub 2018 May 26.

Biostatistics and Epidemiology, Gustave Roussy, Paris, France; University Paris-Saclay, Paris, France. Electronic address:

Background: In ESTIMABL1, a randomised phase 3 trial of radioactive iodine (I) administration after complete surgical resection in patients with low-risk thyroid cancer, 92% of patients had complete thyroid ablation at 6-10 months, defined as a recombinant human thyroid-stimulating hormone (rhTSH)-stimulated serum thyroglobulin concentration of 1 ng/mL or less and normal findings on neck ultrasonography. Equivalence was shown between low-activity (1·1 GBq) and high-activity (3·7 GBq) radioactive iodine and also between the use of rhTSH injections and thyroid hormone withdrawal. Here, we report outcomes after 5 years of follow-up.

Methods: This multicentre, randomised, open-label, equivalence trial was done at 24 centres in France. Between March 28, 2007, and Feb 25, 2010, we randomly assigned (1:1:1:1) adults with low-risk differentiated thyroid carcinoma who had undergone total thyroidectomy to one of four strategies, each combining one of two methods of thyrotropin stimulation (rhTSH or thyroid hormone withdrawal) and one of two radioactive iodine activities (1·1 GBq or 3·7 GBq). Randomisation was by computer-generated sequence, with variable block size. Follow-up consisted of a yearly serum thyroglobulin measurement on levothyroxine treatment. Measurement of rhTSH-stimulated thyroglobulin and neck ultrasonography were done at the discretion of the treating physician. No evidence of disease was defined as serum thyroglobulin of 1 ng/mL or less on levothyroxine treatment and normal results on neck ultrasonography, when performed. This study was registered with ClinicalTrials.gov, number NCT00435851.

Findings: 726 patients (97% of the 752 patients originally randomised) were followed up. At a median follow-up since randomisation of 5·4 years (range 0·5-9·2), 715 (98%) had no evidence of disease. The other 11 had either structural disease (n=4), raised serum thyroglobulin concentration (n=5), or indeterminate findings on neck ultrasonography (n=2). At ablation, six of these patients had received 1·1 GBq radioactive iodine (five after rhTSH and one after withdrawal) and five had received 3·7 GBq (two after rhTSH and three after withdrawal). TSH-stimulated (either after rhTSH injections or thyroid hormone withdrawal according to the treatment group) thyroglobulin concentration measured at the time of ablation was prognostic for structural disease status at ablation, ablation status at 6-10 months, and the final outcome.

Interpretation: Our findings suggest that disease recurrence was not related to the strategy used for ablation. These data validate the use of 1·1 GBq radioactive iodine after rhTSH for postoperative ablation in patients with low-risk thyroid cancer.

Funding: French National Cancer Institute (INCa), French Ministry of Health, and Sanofi Genzyme.
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http://dx.doi.org/10.1016/S2213-8587(18)30113-XDOI Listing
August 2018

Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

Cancer Epidemiol 2018 02 8;52:142-147. Epub 2018 Jan 8.

Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, F-94805, France; Gustave Roussy, Villejuif, F-94805, France; University of Paris-Sud, Villejuif, F-94800, France. Electronic address:

Background: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk.

Methods: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas.

Results: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk.

Conclusion: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.
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http://dx.doi.org/10.1016/j.canep.2017.12.015DOI Listing
February 2018

Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France.

Cancer Epidemiol 2017 06 17;48:78-84. Epub 2017 Apr 17.

CESP (Center for Research in Epidemiology and Population Health), INSERM U1018, Cancer and Environment Team, Université Paris-Saclay, Université Paris-Sud, Villejuif, France. Electronic address:

The three times higher incidence of thyroid cancer in women compared to men points to a role of female sex hormones in its etiology. However the effects of these factors are poorly understood. We analyzed the association between thyroid cancer and hormonal and reproductive factors among women enrolled in CATHY, a population-based case-control study conducted in France. The study included 430 cases of papillary thyroid cancer and 505 controls frequency-matched on age and area of residence. The odds ratios for thyroid cancer increased with age at menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared to premenopausal women, particularly if menopause followed an ovariectomy, and for women with age at menopause <55years. In addition, use of oral contraceptives and menopausal hormone therapy reduced the association with thyroid cancer by about one third, and breastfeeding by 27%. Overall, these findings provide evidence that the risk of thyroid cancer increases with later age at menarche and after menopause, and decreases with use of oral contraceptives and menopausal hormone therapy. These findings confirm an implication of hormonal factors in papillary thyroid cancer risk, whose mechanisms need to be elucidated.
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http://dx.doi.org/10.1016/j.canep.2017.04.001DOI Listing
June 2017

Modeling therapeutic response to radioiodine in metastatic thyroid cancer: a proof-of-concept study for individualized medicine.

Oncotarget 2017 Jun;8(24):39167-39176

Service de Médecine Nucléaire, CHU La Timone, Aix-Marseille Université, 13385 Marseille 05, France.

Purpose: Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions to maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach of this study was to build a mathematical model describing tumor growth with the kinetics of thyroglobulin (Tg) concentrations over time, following RAI for metastatic thyroid cancer.

Experimental Design: Data from 50 patients with metastatic papillary thyroid carcinoma treated within eight French institutions, followed over 3 years after initial RAI treatments, were included in the model. A semi-mechanistic mathematical model that describes the tumor growth under RAI treatment was designed.

Results: Our model was able to separate patients who responded to RAI from those who did not, concordant with the physicians' determination of therapeutic response. The estimated tumor doubling-time (Td was found to be the most informative parameter for the distinction between responders and non-responders. The model was also able to reclassify particular patients in early treatment stages.

Conclusions: The results of the model present classification criteria that could indicate whether patients will respond or not to RAI treatment, and provide the opportunity to perform personalized management plans.
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http://dx.doi.org/10.18632/oncotarget.16637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503603PMC
June 2017

Overdiagnosis of thyroid cancer in the Marne and Ardennes Departments of France from 1975 to 2014.

Ann Endocrinol (Paris) 2017 Feb 15;78(1):27-32. Epub 2016 Sep 15.

Thyroid Cancer Registry, Institut Jean-Godinot, 51100 Reims, France.

Objectives: Incidence of thyroid cancer has increased considerably in France in recent years, but the mortality rate has declined only slightly. Part of this increased incidence could be attributable to overdiagnosis. We aimed to estimate the contribution of overdiagnosis to the incidence of papillary thyroid cancer.

Material And Methods: Incidence rates were calculated based on data from the specialised Marnes-Ardennes thyroid cancer registry, for cancers diagnosed between 1975 and 2014, by age category and by five-year period. The population was divided into two groups according to pTNM classification at diagnosis (i.e. localised or invasive). Overdiagnosis was defined as the difference in incidence rates between the invasive cancer and localised cancer groups. This rate was then divided by the incidence rate in the localised cancer group for the most recent period (2010-2014) to obtain the proportion of cancers attributable to overdiagnosis.

Results: In total, 2008 patients were included. The proportion of incidence attributable to overdiagnosis for the period 2010-2014 was estimated at 7 and 62% in men and women aged < 50 years respectively, and at 65 and 73% respectively in men and women aged ≥ 50 years.

Conclusion: We observed a high proportion of cancers attributable to overdiagnosis. This finding raises the issue of patient management, with the risk of overtreatment, and the repercussions on quality of life for patients diagnosed with cancer.
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http://dx.doi.org/10.1016/j.ando.2016.07.005DOI Listing
February 2017

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

Eur Thyroid J 2016 Jul 21;5(2):132-8. Epub 2016 May 21.

U1018, Centre d'Epidémiologie et de Santé des Populations (CESP), Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Institut Gustave Roussy, Villejuif, France; Université Paris-Saclay, Villejuif, France.

Purpose: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk.

Methods: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status.

Results: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years).

Conclusion: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.
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http://dx.doi.org/10.1159/000445887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949366PMC
July 2016

Fine-mapping of two differentiated thyroid carcinoma susceptibility loci at 9q22.33 and 14q13.3 detects novel candidate functional SNPs in Europeans from metropolitan France and Melanesians from New Caledonia.

Int J Cancer 2016 08 30;139(3):617-27. Epub 2016 Mar 30.

CESP, INSERM, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.

Incidence of differentiated thyroid carcinoma varies considerably between countries and ethnic groups, with particularly high incidence rates in Melanesians of New Caledonia. Differentiated thyroid cancer (DTC) has a familial relative risk higher than other cancers, highlighting the contribution of inherited factors to the disease. Recently, genome-wide association studies (GWAS) identified several DTC susceptibility loci. The most robust associations were reported at loci 9q22 (rs965513 and rs1867277) and 14q13 (rs944289 and rs116909734). In this study, we performed a fine-mapping study of the two gene regions among Europeans and Melanesians from Metropolitan France and New Caledonia. We examined 81 single nucleotide polymorphisms (SNPs) at 9q22 and 561 SNPs at 14q13 in Europeans (625 cases/776 controls) and in Melanesians (244 cases/189 controls). The association with the four SNPs previously identified in GWAS was replicated in Europeans while only rs944289 was replicated in Melanesians. Among Europeans, we found that the two SNPs previously reported at 9q22 were not independently associated to DTC and that rs965513 was the predominant signal; at 14q13, we showed that the haplotype rs944289[C]-rs116909374[C]-rs999460[T] was significantly associated with DTC risk and that the association with rs116909374 differed by smoking status (p-interaction = 0.03). Among Melanesians, a new independent signal was observed at 14q13 for rs1755774 which is strongly correlated to rs2787423; this latter is potentially a functional variant. Significant interactions with parity (p < 0.05) and body mass index were observed for rs1755774 and rs2787423. This study contributed to a better characterization of the DTC loci 9q22 and 14q13 in Europeans and in Melanesians and has identified novel variants to be prioritized for further functional studies.
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http://dx.doi.org/10.1002/ijc.30088DOI Listing
August 2016

Prophylactic neck dissection for low-risk differentiated thyroid cancers: Risk-benefit analysis.

Head Neck 2016 07 13;38(7):1091-6. Epub 2016 Feb 13.

Thyroïde Marne-Ardennes Register, CLCC Institut Jean Godinot, Reims, France.

Background: The benefit of neck dissection is the subject of debate in differentiated thyroid cancer (DTC). We analyze the risk-benefit of neck dissection for low-risk DTC without detectable lymph nodes.

Methods: We conducted a retrospective study from 1983 to 2003; which included 295 patients without detectable lymph nodes who were treated by thyroidectomy with (C+) or without (C-) neck dissection. All patients had iodine131 therapy. We compared the frequency of remission, disease progression, and permanent complications between groups.

Results: Two hundred twelve patients comprised the C+ group, and 83 patients the C- group. Respectively for C+ versus C-, remission rates were 92% versus 89.2% (p = .40), and progressive disease observed was 3.3% versus 7.2% (p = .10). Permanent hypoparathyroidism occurred in 15.1% in C+ versus 3.6% in C- (p = .006).

Conclusion: The risk-benefit analysis of neck dissection in patients with low-risk DTC shows no benefit in terms of complete remission or occurrence of progression. However, risk of complications seems to be higher in patients with neck dissection. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1091-1096, 2016.
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http://dx.doi.org/10.1002/hed.24402DOI Listing
July 2016

Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

Eur J Endocrinol 2016 Apr 15;174(4):491-502. Epub 2016 Jan 15.

Department of Nuclear MedicineLa Timone University Hospital, European and Center for Research in Medical Imaging, Aix-Marseille University, 264 rue Saint-Pierre 13385 Marseille Cedex 5, FranceInserm UMR1068 Marseille Cancerology Research CenterInstitut Paoli-Calmettes, Marseille, FranceDepartment of Endocrinology and Nuclear MedicineGHE-Hospices Civils de Lyon and Lyon 1 University, Lyon, FranceDepartment of Nuclear MedicineLapeyronie University Hospital, Montpellier, FranceUniversity Hospital of BordeauxBordeaux, FranceDepartment of Nuclear MedicineJean Godinot Institute, Reims, FranceDepartment of Nuclear MedicineBrest University Hospital, Brest, FranceDepartment of Nuclear MedicineSaint-Antoine Hospital, Paris, FranceDepartment of Nuclear MedicineSaint-Louis Hospital, Paris, FranceDepartment of Nuclear MedicineUniversity of Nice, Nice, FranceDepartment of Endocrinology and Metabolic DiseasesCHU Larrey, Toulouse University Hospital, Toulouse, FranceDepartment of Public HealthEA3279 Self-perceived Health Assessment Research Unit, La Timone University, Aix-Marseille University, Marseille, France.

Objective: While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon.

Methods: A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety.

Results: The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported.

Conclusion: Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined.
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http://dx.doi.org/10.1530/EJE-15-1099DOI Listing
April 2016

Quality of Life and Cost-Effectiveness Assessment of Radioiodine Ablation Strategies in Patients With Thyroid Cancer: Results From the Randomized Phase III ESTIMABL Trial.

J Clin Oncol 2015 Sep 3;33(26):2885-92. Epub 2015 Aug 3.

Isabelle Borget, Julia Bonastre, Désirée Déandréis, Sophie Leboulleux, Florence Journeau, Ellen Benhamou, and Martin Schlumberger, Gustave Roussy, Villejuif; Isabelle Borget, Julia Bonastre, and Ellen Benhamou, Center for Research in Epidemiology and Population Health, L'Institut National de la Santé et de la Recherche Médicale 1018; Isabelle Borget and Martin Schlumberger, University Paris-Sud; Laurence Leenhardt, Hôpital Pitié-Salpétrière; Marie-Elisabeth Toubert, Hôpital Saint-Louis, Paris; Bogdan Catargi, Centre Hospitalier Universitaire (CHU) Bordeaux; Francoise Bonichon, Institut Bergonié, Bordeaux; Slimane Zerdoud, Centre Claudius Regaud; Delphine Bastie, CHU Toulouse, Toulouse; Daniela Rusu, Centre René Gauducheau, Nantes; Stéphane Bardet, Centre François Baclesse, Caen; Claire Schvartz, Institut Jean Godinot, Reims; Pierre Vera, Centre Becquerel, Rouen; Olivier Morel, Institut de Cancérologie de l'Ouest, Paul Papin, Angers; Daniele Benisvy, Centre Lacassagne, Nice; Claire Bournaud, CHU Lyon, Lyon; and Antony Kelly, Centre Jean Perrin, Clermont-Ferrand, France.

Purpose: In the ESTIMABL phase III trial, the thyroid ablation rate was equivalent for the two thyroid-stimulating hormone (TSH) stimulation methods (thyroid hormone withdrawal [THW] and recombinant human TSH [rhTSH]) and the two iodine-131 ((131)I) activities (1.1 or 3.7 GBq). The objectives of this article were to present health-related quality-of-life (HRQoL) results and a cost-effectiveness evaluation performed alongside this trial.

Patients And Methods: HRQoL and utility were longitudinally assessed, from random assignment to the follow-up visit at 8 ± 2 months for the 752 patients with thyroid cancer, using the Short Form-36 and the EuroQoL-5D questionnaires, respectively. A cost-effectiveness analysis was performed from the societal perspective in the French context. Resource use (hospitalization for (131)I administration, rhTSH, sick leaves, and transportation) was collected prospectively. We used the net monetary benefit approach and computed cost-effectiveness acceptability curves for both TSH stimulation methods and (131)I activities. Sensitivity analyses of the costs of rhTSH were performed.

Results: At (131)I administration, THW caused a clinically significant deterioration of HRQoL, whereas HRQoL remained stable with rhTSH. This deterioration was transient with no difference 3 months later. rhTSH was more effective than THW in terms of quality-adjusted life-years (QALYs; +0.013 QALY/patient) but more expensive (+€474/patient). The probability that rhTSH would be cost effective at a €50,000/QALY threshold was 47% in France. The use of 1.1 GBq of (131)I instead of 3.7 GBq reduced per-patient costs by €955 (US$1,018) but with slightly decreased efficacy (-0.007 QALY/patient).

Conclusion: rhTSH avoids the transient THW-induced deterioration of HRQoL but is unlikely to be cost effective at its current price.
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http://dx.doi.org/10.1200/JCO.2015.61.6722DOI Listing
September 2015

Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

Am J Epidemiol 2015 Aug 30;182(3):202-14. Epub 2015 Jun 30.

The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer.
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http://dx.doi.org/10.1093/aje/kwv048DOI Listing
August 2015

Prognostic value of (18)F-FDG PET/CT metabolic parameters in metastatic differentiated thyroid cancers.

Clin Nucl Med 2015 Jun;40(6):469-75

From the *Service de Médecine Nucléaire, Institut Jean Godinot, Reims; †Unité thyroïde, Institut Jean Godinot, Reims; ‡Unité de Biostatistiques et Qualité de vie, Centre Georges-François Leclerc, Dijon; and §Service de Radiophysique, Institut Jean Godinot, Reims, France.

Purpose: To evaluate the prognostic value of F-fluorodeoxyglucose positron emission tomography (FDG PET) with quantitative analysis using metabolic parameters in metastatic differentiated thyroid cancer (DTC).

Materials And Methods: The FDG-PET scans of 37 patients with metastatic DTC were studied retrospectively. The number of FDG-avid lesions, the SUVmax, the SULpeak of the lesion with the highest FDG uptake, the overall metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) were measured. Curves of progression-free survival (Kaplan-Meier) and Cox univariate and multivariate analyses determined the prognostic factors for survival.

Results: Progression-free survival was better in patients with less than 10 FDG-avid lesions (P = 0.0089), the SUVmax less than 10 (P = 0.0026), the SULpeak less than 5 (P = 0.0004), and the TLG less than 154 (P = 0.0110).Cox analyses showed that only the result of the PET scan was predictive of survival (age, TNM stage, histology, and the I whole body radioiodine scan were not associated with prognosis). In the univariate analysis, prognostic factors for progression-free survival and overall survival were the SUVmax (P = 0.004; P = 0.018), the SULpeak (P = 0.001; P = 0.017), and the TLG (P = 0.014; P = 0.012). The number of FDG-avid lesions was significantly associated with progression-free survival (P = 0.012), but not the MTV. In the multivariate analysis, the number of FDG-avid lesions and the SULpeak were independent prognostic factors.

Conclusions: FDG PET using metabolic parameters is a prognostic factor in metastatic DTC. It could improve the therapeutic management and follow-up of patients.
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http://dx.doi.org/10.1097/RLU.0000000000000780DOI Listing
June 2015

Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial: results from a French cohort.

Thyroid 2015 Apr 18;25(4):386-91. Epub 2015 Feb 18.

1 Department of Nuclear Medicine, Hôpital Saint Louis , Paris, France .

Background: A randomized phase III trial demonstrated that vandetanib treatment is effective in patients with metastatic medullary thyroid cancer (MTC), leading to regulatory approval, but its use may be associated with toxicities that require specific monitoring and management. The objective of the present study performed in France was to describe the toxicity profile and efficacy of vandetanib treatment when given outside any trial.

Methods: Sixty-eight patients were treated with vandetanib in the frame of a temporary use authorization (ATU) in France from August 2010 to February 2012, when the drug was available on request for patients with locally advanced or metastatic MTC. Patients were registered by the French health authorities, and characteristics, treatment parameters, toxicity profile, and efficacy were retrospectively reviewed. Eight patients were excluded from the analysis because vandetanib treatment was not administered (n=3), had been given in a trial before ATU (n=3), or was given for a non-MTC cancer (n=2).

Results: Data from the 60 MTC patients were analyzed. Mean age was 58 years (range 11-83 years), 39 patients were male, and six had hereditary MTC. Fifty-six (93%) had metastatic disease in the mediastinum (82%), bones (65%), liver (53%), or lung (53%), and four had only locally advanced disease. At the time of study evaluation, with a median follow-up of 20 months and a median duration of treatment of 9.7 months (range 0.3-36 months), 15 patients were continuing vandetanib treatment (range 18-36 months). Median progression-free survival was 16.1 months. Twenty-five patients discontinued treatment for disease progression (range 0.3-29 months). Best tumor response was a complete response in one patient, a partial response in 12 (20%), stable disease in 33 (55%), and progression in seven patients (12%). All patients had at least one adverse event (AE) during treatment. The main AEs were skin toxicity, diarrhea, and asthenia. Sixteen patients (27%) discontinued treatment for toxicity, and one patient died from vandetanib-induced cardiac toxicity.

Conclusions: Vandetanib is an effective option for patients with advanced MTC. AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction.
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http://dx.doi.org/10.1089/thy.2014.0361DOI Listing
April 2015

Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study.

Am J Epidemiol 2014 Nov 30;180(10):1007-17. Epub 2014 Sep 30.

The incidence of thyroid cancer has increased in eastern Europe since the Chernobyl nuclear power plant accident. Although the radioactive fallout was much less severe and the thyroid radiation dose was much lower in France, a case-control study was initiated in eastern France. The present study included 633 young women who were diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006 and matched with 677 controls. Face-to-face interviews were conducted from 2005 to 2010. Odds ratios were calculated using conditional logistic regressions and were reported in the total group and by histopathological type of cancer ("only papillary" and "excluding microcarcinomas"). The risk of thyroid cancer was higher in women who had a higher number of pregnancies, used a lactation suppressant, or had early menarche. Conversely, breastfeeding, oral contraceptive use, and late age at first pregnancy were associated with a lower risk of thyroid cancer. No association was observed between thyroid cancer and having irregular menstrual cycle, undergoing treatment for menstrual cycle regularity shortly after menarche, having a cessation of menstruation, use of another contraceptive, history of miscarriage or abortion for the first pregnancy, or having had gestational diabetes. This study confirms the role of hormonal and reproductive factors in thyroid cancer, and our results support the fact that exposure to estrogens increases thyroid cancer risk.
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http://dx.doi.org/10.1093/aje/kwu220DOI Listing
November 2014

Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

N Engl J Med 2012 May;366(18):1663-73

Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy and University Paris-Sud, Villejuif, France.

Background: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care.

Methods: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework.

Results: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods.

Conclusions: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).
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http://dx.doi.org/10.1056/NEJMoa1108586DOI Listing
May 2012

Impact on overall survival of radioactive iodine in low-risk differentiated thyroid cancer patients.

J Clin Endocrinol Metab 2012 May 16;97(5):1526-35. Epub 2012 Feb 16.

Thyroid Cancer Registry, Institut Jean Godinot, 51100 Reims, France.

Context: American Thyroid Association and European Thyroid Association guidelines cannot recommend for or against radioactive iodine (RAI) ablation after surgery in low-risk differentiated thyroid cancer (DTC) patients.

Objectives: The objective of the study was to assess the survival benefit of RAI for these patients.

Design: We identified 1298 DTC patients at low risk treated between 1975 and 2005. Logistic regressions were used to identify variables associated to RAI and to calculate the propensity score to receive RAI after surgery. We compared overall survival (OS) and disease-free survival (DFS) according to RAI with the log-rank tests and univariate and multivariate Cox analyses. Analyses stratified on propensity score were also performed.

Results: Median follow-up was 10.3 yr. Nine hundred eleven patients received RAI after surgery vs. 387 patients without RAI after surgery. Using univariate analysis, 10-yr OS was found to be 95.8% in patients without RAI after surgery vs. 94.6% in RAI after surgery (P = 0.006), and 10-yr DFS was found to be 93.1% vs. 88.7% (P = 0.001). All clinical factors except sex were significantly associated with RAI. Using multivariate Cox analyses, RAI was neither significantly nor independently associated with OS (P = 0.243) and DFS (P = 0.2659). After stratification on propensity score, Cox univariate analyses showed that OS did not differ according to RAI (P = 0.3524), with a hazard ratio for RAI of 0.75 (95% confidence interval 0.40-1.38). Similarly, DFS did not differ (P = 0.48) with a stratified univariate hazard ratio of 1.11 (95% confidence interval 0.73-1.70).

Conclusion: With a long-term follow-up of 10.3 yr, we failed to prove any survival benefit of RAI after surgery in a large cohort of low-risk DTC patients.
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http://dx.doi.org/10.1210/jc.2011-2512DOI Listing
May 2012

Thyroid adenomas and carcinomas following radiotherapy for a hemangioma during infancy.

Radiother Oncol 2009 Nov 8;93(2):377-82. Epub 2009 Jun 8.

Inserm, U605, Villejuif, France.

Background And Purpose: A cohort study was performed to investigate the carcinogenic effect of treating skin hemangioma with ionizing radiation during early childhood. This paper presents the incidence of differentiated thyroid adenomas and carcinomas after radiotherapy in this cohort.

Methods And Materials: Of a total of 8307 patients treated for a skin hemangioma between 1940 and 1973 at the Institut Gustave-Roussy, 4767 were included in an incidence study, among whom 3795 had received radiotherapy. Seventy-three percent were less than 1-year-old at the time of treatment. External radiotherapy, Radium 226, Strontium 90, Yttrium 90, and Phosphorus 32 were used. The radiation dose received by the thyroid during radiotherapy, estimated in 3497 of the 3795 patients using specific software, was 41 mGy on average. Thyroid tumor cases were obtained by sending out a questionnaire, and were verified in pathological reports. Estimates of thyroid cancer specific incidence rates in the French population were obtained from the French cancer registry network. External and internal analyses were performed.

Results: During an average follow-up of 35 years, 11 patients developed a differentiated thyroid carcinoma and 44 a thyroid adenoma. The incidence of thyroid adenoma was found to be higher among taller and heavier individuals. The incidence of both thyroid carcinoma and adenoma was higher among non-smoker patients. A significant dose-response relationship was found between the radiation dose received by thyroid and the risk of thyroid cancer (Excess Relative Risk per GY, ERR/Gy: 14.7, 95%CI: 1.6-62.9) and of adenoma (ERR/Gy: 5.7, 95%CI: 0.7-19.4).

Conclusion: This study confirms that radiation treatment performed in the past for hemangioma during infancy increased the risk of thyroid carcinoma and adenoma. Patients treated with external radiotherapy or with Radium 226 applicators for hemangiomas have to be more specifically followed up because this is the subgroup in whom the highest doses were received by the thyroid gland (more than 90% of the radiation doses were higher than 100 mGy). They are therefore more at risk of developing thyroid cancer.
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http://dx.doi.org/10.1016/j.radonc.2009.05.011DOI Listing
November 2009

Health outcomes of children fathered by patients treated with radioiodine for thyroid cancer.

Clin Endocrinol (Oxf) 2009 Dec 25;71(6):880-3. Epub 2009 Feb 25.

Inserm U605 Institut Gustave Roussy Université Paris XI, Villejuif, France.

Context And Objectives: Radiation is known to be mutagenic. The present study analyses birth outcomes and the health of offspring from men previously exposed to (131) I treatment for thyroid carcinoma.

Methods: Data on 493 pregnancies (356 from 173 untreated fathers, 23 from 17 patients who have undergone surgery alone and 114 from 63 fathers who received (131) I) were obtained by interviewing male patients treated for thyroid carcinoma who had not received significant external radiation to the testes. Among these pregnancies, 73 were conceived from fathers who had received more than 370 MBq.

Results: The mean activity for the 114 pregnancies fathered by 63 patients was 3993 MBq leading to an estimated radiation dose of 9.2 cGy to the testes (MIRD committee coefficient). No significant differences between untreated and treated fathers were found for any adverse outcome.

Conclusion: There was no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring, whatever the event considered. As our study is underpowered, the question of whether testicular irradiation, fractionated or not, is linked to impaired fertility or consequences on offspring remains to be established.
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http://dx.doi.org/10.1111/j.1365-2265.2009.03561.xDOI Listing
December 2009

SPECT/CT in localization of parathyroid adenoma or hyperplasia in patients with previous neck surgery.

Clin Nucl Med 2008 Jun;33(6):394-7

Service de Médecine Nucléaire, Institut Jean Godinot, Centre Hospitalier et Universitaire de Reims, France.

Purpose: Single photon emission computed tomography/computed tomography (SPECT/CT) now makes it possible to use combined morphologic CT and functional scintigraphy information. It has proved useful for localization of abnormal parathyroid glands, especially in the case of an ectopic gland. We experienced that it was also beneficial for patients with a history of previous neck surgery, and we report 4 cases in this entity.

Materials And Methods: Four patients with prior neck surgery and hyperparathyroidism underwent parathyroid Tc-99m MIBI scintigraphy with SPECT/CT. Two patients had undergone surgery for hyperparathyroidism and 2 had undergone thyroidectomy, 1 for thyroid cancer and 1 for multinodular goiter. Parathyroid hormone levels were assessed during surgery, and patients were followed several months after treatment.

Results: SPECT/CT successfully localized the abnormal gland, including an uncommon anterior situation for which previous surgery guided by planar imagery failed to cure the hyperparathyroidism. It allowed efficient surgical treatment, as confirmed by parathyroid hormone level normalization, without complications and with a relatively short operation time in those challenging cases.

Conclusions: SPECT/CT seems to be a useful tool for presurgical assessment in hyperparathyroidism, not only for ectopic glands but also for patients with previous neck surgery.
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http://dx.doi.org/10.1097/RLU.0b013e318170d4a5DOI Listing
June 2008

Therapeutic administration of 131I for differentiated thyroid cancer: radiation dose to ovaries and outcome of pregnancies.

J Nucl Med 2008 May 15;49(5):845-52. Epub 2008 Apr 15.

INSERM U605, Villejuif, France.

Unlabelled: Radiation is known to be mutagenic. The present study updates a 10-y-old study regarding pregnancy outcome and the health of offspring of women previously exposed to radioiodine ((131)I) during thyroid carcinoma treatment, by doubling the number of pregnancies that occurred after exposure.

Methods: Data on 2,673 pregnancies were obtained by interviewing female patients who were treated for thyroid carcinoma but had not received significant external radiation to the ovaries.

Results: The incidence of miscarriages was 10% before any treatment for thyroid cancer; this percentage increased after surgery for thyroid cancer, both before (20%) and after (19%) (131)I treatment, with no variation according to the cumulative dose. In contrast to previously reported data, miscarriages were not significantly more frequent in women treated with radioiodine during the year before conception, not even in women who had received more than 370 MBq during that year. The incidences of stillbirths, preterm births, low birth weight, congenital malformations, and death during the first year of life were not significantly different before and after (131)I therapy. The incidences of thyroid and nonthyroid cancers were similar in children born either before or after the mother's exposure to radioiodine.

Conclusion: There is no evidence that exposure to radioiodine affects the outcomes of subsequent pregnancies and offspring. The question as to whether the incidences of malformations and thyroid and nonthyroid cancers are related to gonadal irradiation remains to be established. The doubling dose is still being heatedly debated, and the value of 1 Gy as the doubling dose in humans should be reevaluated.
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http://dx.doi.org/10.2967/jnumed.107.046599DOI Listing
May 2008

Cancer prevalence in France: time trend, situation in 2002 and extrapolation to 2012.

Eur J Cancer 2008 Jan 26;44(1):115-22. Epub 2007 Nov 26.

Network of French Cancer Registries (FRANCIM), Toulouse, France.

Background: Cancer prevalence is a basic indicator of the cancer burden in a population and essential to estimate the resources needed for care of cancer patients. This paper provides a prevalence estimate for 2002 and 2012 in France and an assessment of the trend in prevalence over the period 1993-2002.

Method: Incidence and survival data from French cancer registries were used to estimate specific 5-year partial prevalence rates that were then applied to the whole French population.

Results: In 2002, the 5-year partial prevalence was over 427,000 in men and 409,000 in women. The most frequent cancer site among men was prostate (35% of the cases) and breast in women (45% of the cases). In 2002, in France, more than 3.5% of men over 74 years old are alive with a prostatic cancer diagnosed within 5 years. The increase in the number of cases between 1993 and 2002 was about 40% and was mainly due to prostate and breast cancers. The demographic variations alone induce an increase of the number of prevalent cases of 75,000 among men and 54,500 among women if both incidence and survival are considered as stable during the period 2002-2012.

Conclusion: This study uses a large amount of information from cancer registries which makes it possible to assess the cancer burden. Five-year prevalence is very sensitive to changes in incidence and demographic changes. Prevalence has to be estimated regularly in order to ensure accurate medical care meets demand.
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http://dx.doi.org/10.1016/j.ejca.2007.10.022DOI Listing
January 2008

[An unusual tumor of the ovary].

Ann Pathol 2006 Feb;26(1):39-40

Service d'Anatomie et Cytologie Pathologiques, Hôpital Robert Debré, CHU de Reims, Avenue du Général Koenig, 51092 Reims Cedex.

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http://dx.doi.org/10.1016/s0242-6498(06)70660-5DOI Listing
February 2006

Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma.

Int J Radiat Oncol Biol Phys 2005 Jul;62(4):1084-9

National Institute of Public Health and Medical Research, INSERM, Unit 605, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.

Purpose: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure.

Methods And Materials: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOS_Eg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation.

Results: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by (131)I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9).

Conclusions: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors.
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http://dx.doi.org/10.1016/j.ijrobp.2004.12.063DOI Listing
July 2005