Association of BRAF V600E Mutant Allele Proportion with the Dissemination Stage of Papillary Thyroid Cancer.

The early identification of aggressive forms of cancer is of high importance in treating papillary thyroid cancer (PTC). Disease dissemination is a major factor influencing patient survival. Mutation status of BRAF oncogene, BRAF V600E, is proposed to be an indicator of disease recurrence; however, its influence on PTC dissemination has not been deciphered. This study aimed to explore the association of the frequency of BRAF V600E alleles in PTC with disease dissemination. In this study, 173 PTC samples were analyzed, measuring the proportion of BRAF V600E alleles by qPCR, which was then normalized against the proportion of tumor cells. Semiquantitative analysis of BRAF V600E mutant protein was performed by immunohistochemistry. The BRAF V600E mutation was present in 60% of samples, while the normalized frequency of mutated BRAF alleles ranged from 1.55% to 92.06%. There was no significant association between the presence and/or proportion of the BRAF V600E mutation with the degree of PTC dissemination. However, the presence of the BRAF mutation was significantly linked with angioinvasion. This study's results suggest that there is a heterogeneous distribution of the BRAF mutation and the presence of oligoclonal forms of PTC. It is likely that the BRAF mutation alone does not significantly contribute to PTC aggressiveness.

Recent data on iodine intake in Croatian schoolchildren: results of 2014-2019 survey.

BACKGROUND: Both insufficient and excessive iodine intake can lead to a broad range of disorders. A cross-sectional survey was conducted to assess iodine status in schoolchildren from Croatia. DESIGN: 957 healthy 6 to 12-year-olds were enrolled (381 from northwestern region, 190 from eastern region, 215 from north Adriatic, and 171 from central Dalmatia region). Urinary iodine concentration (UIC) was measured in spot urine samples. Thyroid volume (Tvol) was recorded by ultrasound device. Standard anthropometric measures were taken, and body surface area (BSA) was determined. Tvol medians were calculated as a function of age, sex and BSA and compared with reference values. RESULTS: Total sample size included 490 boys and 467 girls. Overall median UIC was 250.68 µg/L, with statistically significant variance in geographical regions (median UIC was 244.71 µg/L in northwestern, 208.02 µg/L in eastern, 216.07 µg/L in north Adriatic and 366.43 µg/L in central Dalmatia region). There were 10.08% of samples with UIC < 100 mcg/L while 38.24% of samples had UIC > 300 mcg/L. Age-matched Tvol medians in schoolchildren from all regions of Croatia were at the upper limits of reference values, but in north Adriatic and central Dalmatia exceeded the 97th percentile. BSA-matched Tvol was within the reference range in all regions. CONCLUSIONS: Our results demonstrate sufficient (more than adequate) iodine intake in schoolchildren of Croatia, and excessive iodine intake in central Dalmatia region. Total thyroid volumes in schoolchildren of Croatia were within the normal range, however borderline enlarged age-matched thyroid glands were observed in coastal areas.

SIMULTANEOUS METASTASES OF PAPILLARY THYROID CARCINOMA AND NEUROENDOCRINE TUMOR OF THE CECUM TO CERVICAL LYMPH NODES: A CASE REPORT.

We present a case of a patient with simultaneous cervical lymph node metastasis of papillary thyroid cancer (PTC) and cecum neuroendocrine tumor (NET). A 45-year-old male patient with the diagnosis of metastatic NET of the cecum underwent fine needle aspiration (FNA) of a positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) positive nodule in the left thyroid lobe. Due to FNA finding suspect of PTC, the patient underwent total thyroidectomy with central neck dissection. Histopathologic finding revealed PTC of the left thyroid lobe and small solitary lymph node PTC metastasis in the central neck region. Postoperative evaluation with neck ultrasound (US) revealed two enlarged suspected lymph nodes in cervical regions III and IV on the left side of the neck and the patient underwent FNA with measurement of thyroglobulin (Tg) in the aspirates. The FNA finding of the cervical lymph node in the region III revealed PTC metastasis with high Tg value in the aspirate, while FNA finding of the cervical lymph node in the region IV revealed NET metastasis with low Tg value in the aspirate. Postoperative serum Tg value was 17.75 µg/L and the patient underwent 5550 MBq iodine-131 (I-131) therapy. A year after I-131 therapy, follow-up neck US demonstrated complete cure of PTC cervical lymph node metastasis in the region III and stable in size NET cervical lymph node metastasis in the region IV. To our knowledge, this is the first report of simultaneous occurrence of cervical lymph node metastases of PTC and NET of the cecum.

THE PREVALENCE OF SUBCLINICAL HYPOTHYROIDISM IN THE POPULATION OF ELDERLY NURSING HOME RESIDENTS IN ZAGREB.

The aim of the study was to investigate the prevalence of thyroid dysfunction, positive thyroid peroxidase antibodies (TPOAb) and hypercholesterolemia in elderly and younger subjects, and the association of subclinical hypothyroidism with hypercholesterolemia. The study included 204 elderly (136 females and 68 males, age median 71, range 60-92 years), and 83 younger control subjects (63 females and 20 males, age median 45, range 19-55 years). Subjects with prior thyroid dysfunction were excluded. Serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), TPOAb, total cholesterol, height and weight were measured. Mann-Whitney, χ2-test and Student's t-test were used on statistical analysis. The prevalence of subclinical hypothyroidism (TSH >5 mU/L) in elderly was 7.4% vs. 3.6% in younger subjects, with the highest prevalence of 8.8% in elderly women vs. 4.8% in younger women, and 4.4% in elderly men. The prevalence of hypothyroidism and subclinical hyperthyroidism in elderly subjects was 0.5% and 1.5%, respectively. In women with subclinical hypothyroidism, the prevalence of TPOAb was 77% in elderly women and 67% in younger women (overall 19.9% in elderly and 14.3% in younger women). The mean FT3 level was lower in elderly women as compared with elderly men (p<0.01) and younger women (p<0.05). The mean cholesterol level was higher in elderly subjects in comparison with younger ones (p<0.01), and in elderly women vs. elderly men (p<0.01), but without difference between subclinical hypothyroidism and euthyroid subjects (6.0 mmol/L). In conclusion, subclinical hypothyroidism is the most prevalent thyroid dysfunction in elderly, with the highest prevalence in elderly women, and autoimmune thyroiditis is the most common etiology. Hypercholesterolemia was more related to older age, especially elderly females, but not influenced by subclinical hypothyroidism.

Long-Term Outcome of Differentiated Thyroid Cancer Patients-Fifty Years of Croatian Thyroid Disease Referral Centre Experience.

Background: Indolent nature but a high incidence of differentiated thyroid cancer (DTC) remains a challenge for optimizing patient care. Therefore, prognostic factors present valuable information for determining an adequate clinical approach. Methods: This study assessed prognostic features of 1167 papillary (PTC) and 215 follicular (FTC) thyroid cancer patients that had undergone surgery between 1962 and 2012, and were followed-up up to 50 years in a single institution, till April 2020. Age, gender, tumor size, presence of local and distant metastases at presentation, extrathyroidal extension, disease recurrence, and cancer-specific survival were evaluated. Results: In multivariate analysis, factors affecting the worse outcome were age (p = 0.005), tumor size (p = 0.006), and distant metastases (p = 0.001) in PTC, while extrathyroidal extension (p < 0.001), neck recurrence (p = 0.002), and distant metastases (p < 0.001) in FTC patients. Loco-regional recurrence rate was 6% for PTC and 4.7% for FTC patients, while distant metastases were detected in 4.2% PTC and 14.4% of FTC patients. The 10-year cancer-specific survival rates for PTC and FTC were 98.6% and 89.8%, respectively (p < 0.001). Conclusions: Negative prognostic factors, besides distant metastases, were older age and greater tumor size in PTC, and extrathyroidal extension and neck recurrence in FTC patients. The recurrence and mortality rates were very low.

Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration.

Objective: Registers of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. Design: Register-based cross-sectional study. Methods: National register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. Results: Register data on ≥1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. Conclusions: The collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.

IODINE STATUS AND THYROID FUNCTION IN LACTATING WOMEN AND INFANTS - A SURVEY IN THE ZAGREB AREA, CROATIA.

Lactating women (LW) and infants have high dietary iodine requirements and are at risk of iodine deficiency. The aim of the study was to assess iodine status and thyroid function in LW and their breastfed infants in Zagreb, Croatia. The study included 133 LW and breastfed infant pairs. Urinary iodine concentration (UIC) and thyroid function parameters were measured in all subjects. In LW, breast milk iodine concentration (BMIC) was measured and iodine and salt rich food frequency questionnaire data were collected. Results of analysis indicated that 99.2% of the LW used iodized salt in household and 20.4% used iodine-containing vitamin and mineral supplements. Median (IQR) UIC was 75 µg/L (19.0-180.5 µg/L) in LW and 234 µg/L (151.0-367.5 µg/L) in infants, whereas BMIC was 121 µg/kg (87.8-170.8 µg/kg). Multivariate regression analysis revealed BMIC to be a significant predictor of infant UIC (p<0.001). Positive correlation was recorded between LW and infant thyroid function. This was the first study in Croatia demonstrating BMIC to be a reliable biomarker of iodine status during lactation and predicting iodine intake in breastfed infants. The study confirmed that mandatory salt iodization in Croatia ensured sufficient dietary iodine for LW and optimal iodine intake for breastfed infants via breast milk.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Malignancy risk with atypia of undetermined significance finding on thyroid nodule FNA: clinical experience from a tertiary institution.

The Bethesda System for Reporting Thyroid Cytopathology from 2009 introduced a new category in thyroid nodule fine-needle aspiration (FNA) findings named atypia of undetermined significance (AUS), which usually appears in around 5% of FNA findings. Our study aimed to assess the utility of AUS finding in determining the risk of malignancy in thyroid nodules. In our study, 160 patients with AUS finding on initial FNA were regularly followed-up. Total and specific malignancy rates were calculated after receiving histopathologic confirmation or histopathologic/cytologic exclusion of malignancy. Eventually 80 (50%) patients were referred to surgery, with malignancy rate of 37.5% on histopathology. Another 52 (32.5%) patients were confirmed to have benign nodules on repeat FNA. After combining results obtained from histopathologic reports with those obtained from cytologic follow-up, total malignancy rate was 22.72%. However, malignancy was confirmed in only one (5.26%) of 19 patients with AUS finding on repeat FNA with surgical and histopathologic follow-up. In conclusion, FNA is an extremely useful tool for clinicians to discriminate patients to be referred to surgery and those that can be followed-up safely without the need for further invasive procedures.

Corrigendum to: Analytical evaluation of the new Seal Autoanalyzer 3 High Resolution for urinary iodine determination.

[This corrects the article DOI: 10.11613/BM.2019.020711.].

DIFFERENTIATED THYROID CANCER IN PEDIATRIC POPULATION (≤18 YEARS): POSTOPERATIVE TREATMENT WITH RADIOACTIVE IODINE (I-131).

The aim is to present data on the treatment and follow-up in a cohort of patients with pediatric thyroid cancer who underwent total thyroidectomy and received postoperative radioactive iodine (I-131) therapy. The study was conducted in a tertiary high-volume thyroid center, in pediatric patients with differentiated thyroid cancer who were consecutively treated during the 1965-2015 period. A total of 45 patients aged ≤18 years having undergone total thyroidectomy with or without selective neck dissection were included in the study. Decision on postoperative I-131 ablation was based on tumor characteristics, postoperative thyroglobulin level, preablative whole body scintigraphy, and/or neck ultrasound. Median age at diagnosis was 15 years. The presence of cervical lymph node metastases was significantly associated with papillary thyroid cancer, larger tumor size, involvement of two thyroid lobes, and multifocal disease. The presence of distant metastases was significantly associated with larger tumor size. None of the patients died during follow-up period, and the 5-year and 10-year overall survival rates were 100%. The 5-year and 10-year progression-free survival (PFS) rates were 87% and 73%, respectively. Male gender (p=0.046), age ≤15 years (p=0.029) and tumor size >15 mm (p=0.042) were significantly associated with inferior PFS. A significant positive trend of increase in the number of newly diagnosed patients was observed over time (p=0.011). Clinical management of pediatric thyroid cancer is challenging, especially in the light of increasing incidence in this population. Male patients younger than 15 years and with tumors of more than 15 mm in size require additional caution due to lower PFS observed.

Analytical evaluation of the new Seal Autoanalyzer 3 High Resolution for urinary iodine determination.

INTRODUCTION: The aim of the study was to evaluate the analytical performance of the new colorimetric, automatic analyser, Seal AutoAnalyzer 3 High Resolution (Seal AA3 HR) (Seal Analytical, Wisconsin, USA) for urinary iodine measurement. MATERIALS AND METHODS: This study included testing of several analytical features of the method involving: imprecision (within-run %CVr, between-run %CVb and total laboratory precision %CVl), measurement uncertainty, carryover, linearity and method comparison, with 70 urine samples including the measuring range (20 - 700 µg/L). RESULTS: Within-run, %CVb and %CVl of two control levels were 2.03% and 3.04%, 0.51% and 2.61%, and 2.09% and 4.01%, respectively. Carryover effect was less than 1%. The linearity was good in the range of urinary iodine values between 60 and 500 µg/L (R2 = 0.99). Good agreement of urinary iodine values was found between manual technique and Seal AA3 HR, using Passing-Bablok regression (y = 7.84 (- 3.00 to 15.29) + 0.95 (0.90 to 1.00) x) and Blant-Altman test. Cusum test for linearity indicates that there is no significant deviation from linearity (P > 0.1). CONCLUSIONS: The obtained results proved excellent precision, reproducibility and linearity, comparable to the already used, manual method. The New Seal AA3 HR automatic analyser is acceptable for urinary iodine measurement with very good analytical characteristics and can be used for urinary iodine epidemiological studies of the Croatian population.

HMGA2 Gene Expression in Fine-needle Aspiration Samples of Thyroid Nodules as a Marker for Preoperative Diagnosis of Thyroid Cancer.

There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction. The results were evaluated against the postoperative histopathologic diagnosis or definitive cytologic diagnosis in cases of nodular goiter and Hashimoto thyroiditis. Among 237 samples from patients with thyroid nodules that were analyzed, 231 were adequate for real-time reverse transcription polymerase chain reaction analysis. With a cutoff value of 8.71 for relative gene expression, HMGA2 was positive in 19 (16.4%) of 116 nodular goiter, 1 (2.6%) of 39 Hashimoto thyroiditis, 9 (28.1%) of 32 follicular adenoma, 0 (0%) of 5 Hurthle cell adenoma, 32 (88.9%) of 36 papillary carcinoma, and 3 (100%) of 3 follicular carcinoma samples. In discriminating between malignant and benign thyroid nodules, HMGA2 has shown specificity of 84.5%, sensitivity of 91.9%, positive predictive value of 53.1%, and negative predictive value of 98.2%. High sensitivity and negative predictive value of HMGA2 for preoperative detection of malignant thyroid nodules shown in this study indicate that it may have a role as an ancillary marker in cytology in the management of patients with thyroid nodules.

Universal Salt Iodization Provides Sufficient Dietary Iodine to Achieve Adequate Iodine Nutrition during the First 1000 Days: A Cross-Sectional Multicenter Study.

Background: Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d. Objective: We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups. Methods: We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk. Results: The salt iodine concentration was low (<15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (>40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia. Conclusions: Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

THYROGLOBULIN AS A TUMOR MARKER IN DIFFERENTIATED THYROID CANCER - CLINICAL CONSIDERATIONS.

- Initial treatment of the majority of patients with differentiated thyroid cancer (DTC) includes total thyroidectomy. Postoperative ablation therapy with radioactive iodine (I-131) is indicated in all high-risk patients, however, there is disagreement regarding its use in low- and intermediate-risk patients. Over the last few decades, thyroglobulin (Tg) has been established as the primary biochemical tumor marker for patients with DTC. Thyroglobulin can be measured during thyroid hormone therapy or after thyroid-stimulating hormone (TSH) stimulation, through thyroid hormone withdrawal or the use of human recombinant TSH. In many studies, the cut-off value for adequate Tg stimulation is a TSH value ≥30 mIU/L. However, there is an emerging body of evidence suggesting that this long-established standard should be re-evaluated, bringing this threshold into question. Recently, a risk stratification system of response to initial therapy (with four categories) has been introduced and Tg measurement is one of the main components. The relationship between the Tg/TSH ratio and the outcome of radioiodine ablation has also been studied, as well as clinical significance of serum thyroglobulin doubling-time. The postoperative serum Tg value is an important prognostic factor that is used to guide clinical management, and it is the most valuable tool in long term follow-up of patients with DTC.

Breast Milk Iodine Concentration Is a More Accurate Biomarker of Iodine Status Than Urinary Iodine Concentration in Exclusively Breastfeeding Women.

Background: Iodine status in populations is usually assessed by the median urinary iodine concentration (UIC). However, iodine is also excreted in breast milk during lactation; thus, breast milk iodine concentration (BMIC) may be a promising biomarker of iodine nutrition in lactating women. Whether the mammary gland can vary fractional uptake of circulating iodine in response to changes in dietary intake is unclear.Objective: We evaluated UIC and BMIC as biomarkers for iodine status in lactating women with a wide range of iodine intakes.Methods: We recruited 866 pairs of lactating mothers and exclusively breastfed infants from 3 iodine-sufficient study sites: Linfen, China (n = 386); Tuguegarao, Philippines (n = 371); and Zagreb, Croatia (n = 109). We also recruited iodine-deficient lactating women from Amizmiz, Morocco (n = 117). We collected urine and breast milk samples and measured UIC and BMIC.Results: In the 3 iodine-sufficient sites, a pooled regression analysis of the estimated iodine excretion revealed higher fractional iodine excretion in breast milk than in urine at borderline low iodine intakes. In contrast, in the iodine-deficient site in Morocco, a constant proportion (∼33%) of total iodine was excreted into breast milk.Conclusions: In iodine-sufficient populations, when iodine intake in lactating women is low, there is increased partitioning of iodine into breast milk. For this reason, maternal UIC alone may not reflect iodine status, and BMIC should also be measured to assess iodine status in lactating women. Our data suggest a BMIC reference range (2.5th and 97.5th percentiles) of 60-465 µg/kg in exclusively breastfeeding women. This trial was registered at clinicaltrials.gov as NCT02196337.

Dried Blood Spot Thyroglobulin as a Biomarker of Iodine Status in Pregnant Women.

Context: Thyroglobulin (Tg) could be a sensitive biomarker of iodine nutrition in pregnant women (PW). A dried blood spot (DBS) assay would simplify collection and transport in field studies. Objectives: Our aims were to (1) establish and test a reference range for DBS-Tg in PW; (2) determine whether co-measurement of Tg antibodies (Abs) is necessary to define population iodine status. Design, Setting, and Participants: Standardized cross-sectional studies of 3870 PW from 11 countries. For the DBS-Tg reference range, we included TgAb-negative PW (n = 599) from 3 countries with sufficient iodine intake. Main Outcome Measures: We measured the urinary iodine concentration and DBS thyroid-stimulating hormone, total thyroxin, Tg, and TgAb. Results: In the reference population, the median DBS-Tg was 9.2 µg/L (95% confidence interval, 8.7 to 9.8 µg/L) and was not significantly different among trimesters. The reference range was 0.3 to 43.5 µg/L. Over a range of iodine intake, the Tg concentrations were U-shaped. Within countries, the median DBS-Tg and the presence of elevated DBS-Tg did not differ significantly between all PW and PW who were TgAb-negative. Conclusions: A median DBS-Tg of ∼10 µg/L with <3% of values ≥44 µg/L indicated population iodine sufficiency. Concurrent measurement of TgAb did not appear necessary to assess the population iodine status.

Prediction of radioactive iodine remnant ablation failure in patients with differentiated thyroid cancer: A cohort study of 740 patients.

BACKGROUND: The purpose of this study was to detect parameters that could serve as predictors of radioactive iodine (I-131) ablation failure in patients with low-risk and intermediate-risk differentiated thyroid carcinoma (DTC). METHODS: Our cohort study included 740 patients with DTC who received postoperative I-131 remnant ablation. Anthropometric, biochemical, and pathohistological parameters were analyzed and correlated with ablation outcome using multivariable logistic regression models. RESULTS: Treatment failure rates were higher in patients <53 years, with N1a classification, and lymph node capsular invasion. In patients with N1a disease, thyroglobulin (Tg) > 2.4 ng/mL predicted treatment failure with 93.8% sensitivity and 52.5% specificity, and in patients with N1b disease, Tg > 14.9 ng/mL with 77.8% sensitivity and 92.9% specificity. I-131 activity was not associated with treatment outcome. CONCLUSION: Patients < 53 years old, with higher Tg levels, N1a classification, and lymph node capsular invasion have a higher risk of ablation failure. Stimulated Tg is an excellent predictor of treatment failure in patients with N1 disease. © 2016 Wiley Periodicals, Inc. Head Neck 39: 109-115, 2017.

A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer.

BACKGROUND: We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC) and report the first prospective extended RAS analysis in a phase 3 trial. METHODS: Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg-1 Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint. RESULTS: Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR=0.73; 95% CI=0.57-0.93; P=0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR=0.70; 95% CI=0.53-0.93; P=0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR=0.99; 95% CI=0.49-2.00). No new safety signals were observed. CONCLUSIONS: Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wild-type RAS mCRC, validating previous retrospective analyses.