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Abstract Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. This study aimed to demonstrate the ultrasonographic (US) features of TERT promoter-mutated follicular thyroid cancer (FTC) and evaluate their predictive performance. A total of 63 patients with surgically confirmed FTC between August 1995 and April 2021 were included. All data were available for analysis of preoperative US findings and TERT promoter mutation results. Genomic DNA was extracted from the archived surgical specimens to identify TERT promoter mutations. Logistic regression analysis was performed to compare US findings between TERT promoter-mutated and wild-type FTCs. Of the 63 patients with FTC, 10 (15.9%) had TERT promoter mutations. TERT promoter-mutated FTCs demonstrated significantly different US suspicion categories compared to wild-type FTCs (Ps = 0.0054 for K-TIRADS and 0.0208 for ACR-TIRADS), with a trend toward an increasing prevalence of the high suspicion category (40.0% for both K-TIRADS and ACR-TIRADS; Ps for trend = 0.0030 for K-TIRADS and 0.0032 for ACR-TIRADS). Microlobulated margins and punctate echogenic foci were independent risk factors associated with TERT promoter mutation in FTC (odds ratio = 9.693, 95% confidence interval = 1.666–56.401, p = 0.0115 for margins; odds ratio = 8.033, 95% confidence interval = 1.424–45.309, p = 0.0182 for punctate echogenic foci). There were no significant differences in the composition and echogenicity of the TERT promoter-mutated and wild-type FTCs. TERT promoter-mutated FTCs were categorized more frequently as high suspicion by the K-TIRADS and ACR-TIRADS. Based on US findings, the independent risk factors for TERT promoter mutations in FTC are microlobulated margins and punctate echogenic foci.

Parathyroid glands are small endocrine glands that regulate calcium metabolism by producing parathyroid hormone (PTH). These are located at the back of the thyroid gland. Typically, four glands comprise the parathyroid glands, although their numbers may vary among individuals. Parathyroid diseases are related to parathyroid gland dysfunction and can be caused by problems with the parathyroid gland itself or abnormal serum calcium levels arising from renal disease. In recent years, as comprehensive health checkups have become more common, abnormal serum calcium levels are often found incidentally in blood tests, after which several additional tests, including a PTH test, ultrasonography (US), technetium-99m sestamibi parathyroid scan, single-photon-emission CT (SPECT)/CT, four-dimensional CT (4D-CT), and PET/CT, are performed for further evaluation. However, the parathyroid gland remains an organ less familiar to radiologists. Therefore, the normal anatomy, pathophysiology, imaging, and clinical findings of the parathyroid gland and its associated diseases are discussed here.

Abstract Current guidelines recommend total thyroidectomy with central lymph node dissection (CND) for patients with medullary thyroid carcinoma (MTC). This study aimed to identify low-risk MTC patients who may be candidates for lobectomy. We retrospectively reviewed MTC patients who underwent primary surgery at a tertiary referral center from 1998 to 2019. Eighty-five MTC patients were enrolled, excluding patients with primary tumor size > 2.0 cm. Among them, one (1.2%) patient had bilateral tumors. During a median follow-up of 84 months, 12 of the 85 patients experienced structural recurrence. 13 patients had occult lymph node metastasis, and structural recurrence occurred in 2 patients. Factors that significantly affected disease-free survival were clinical N stage (cN0 vs. cN1, log-rank P 250 pg/mL, P = 0.017). After categorizing patients into four groups, patients with preoperative calcitonin levels > 250 pg/mL and cN1 or pN1 had a significantly worse prognosis. Patients with a primary tumor size of 2 cm or less, cN0, and preoperative calcitonin of 250 pg/mL or less can be classified as low-risk MTC patients. We used preoperative clinical information to identify low-risk MTC patients. Lobectomy with prophylactic CND may be a potential therapeutic approach.

Purpose This study compared the malignancy risk of intermediate suspicion thyroid nodules according to the presence of suspicious ultrasonographic (US) findings. Methods From January 2014 to December 2014, 299 consecutive intermediate suspicion thyroid nodules in 281 patients (mean age, 50.6±12.5 years) with final diagnoses were included in this study. Two radiologists retrospectively reviewed the US findings and subcategorized the intermediate suspicion category into nodules without suspicious findings and nodules with suspicious findings, including punctate echogenic foci, nonparallel orientation, or irregular margins. The malignancy rates were compared between the two subcategory groups. Results Of the 299 intermediate suspicion thyroid nodules, 230 (76.9%) were subcategorized as nodules without suspicious findings and 69 (23.1%) as nodules with suspicious findings. The total malignancy rate was 33.4% (100/299) and the malignancy rate of nodules with suspicious findings was significantly higher than that of nodules without suspicious findings (47.8% vs. 29.1%, P=0.004). In nodules with suspicious findings, the most common suspicious finding was punctate echogenic foci (48/82, 58.5%) followed by nonparallel orientation (22/82, 26.8%) and irregular margins (12/82, 14.6%). Thirteen nodules had two suspicious findings simultaneously. A linearly increasing trend in the malignancy rate was observed according to the number of suspicious US findings (P for trend=0.001). Conclusion Intermediate suspicion thyroid nodules with suspicious findings showed a higher malignancy rate than those without suspicious findings. Further management guidelines for nodules with suspicious findings should differ from guidelines for nodules without suspicious findings, even in the same US category.

Abstract Although anaplastic thyroid carcinoma (ATC) is a fatal form of thyroid cancer with an overall survival of only a few months, there are some factors associated with longer survival. However, it remains unknown whether asymptomatic ATC differs from symptomatic ATC in terms of characteristics and overall prognosis. Therefore, we aimed to examine the clinicopathological characteristics and prognosis of asymptomatic ATC compared with those of symptomatic ATC. We retrospectively reviewed the medical records of 113 patients with ATC who were registered at our institution between November 1994 and July 2020. A total of 86 patients (59 women and 27 men; mean age, 66.9 ± 11.1 years) were enrolled for analysis. The clinicopathological characteristics of the ATC cohort were evaluated, and prognostic factors associated with disease-specific mortality were assessed. Of the 86 patients with ATC, 78 were symptomatic and eight were asymptomatic. Compared with the symptomatic group, the asymptomatic group had a younger age at diagnosis (59.3 ± 10.3 vs. 67.7 ± 11.0 years, p = 0.045), smaller tumor size (2.8 ± 1.2 vs. 5.8 ± 2.0 cm, p

Purpose This study investigated the ultrasound (US) features of malignancy in patients with Hürthle cell neoplasms (HCNs) of the thyroid gland. Methods The present study included 139 HCNs that had undergone surgical excision at a single institution from 1996 to 2020 and had preoperative US images. The sonographic characteristics of HCNs were correlated with their pathological results. The US findings associated with malignancy were explored using logistic regression analysis, and the diagnostic performance and cutoff were assessed using receiver operating characteristic analysis. Results The most common US findings of HCNs were a solid content (76.3%), oval to round shape (100%), hypoechogenicity (70.5%), a smooth margin (95.0%), the halo sign (90.6%), and no calcifications (93.5%). HCNs were commonly smaller in pathologic measurements than in US measurements (smaller, same, and greater than US measurements in 60.4%, 21.6%, and 18.0% of HCNs, respectively; P3.35 cm might be used as a criterion to suggest malignancy. The size of HCNs often showed discrepancies between US and pathologic measurements.

Purpose The prevalence of the tall cell variant of papillary thyroid carcinoma (TCVPTC), which has a poor prognosis, has increased as its definition has been modified. We sought to investigate whether TCVPTC is different from the classic type on ultrasonography (US). Methods This study included 46 consecutive TCVPTC patients and 92 classic papillary thyroid carcinoma (PTC) patients who were confirmed surgically at the authors’ institution. The US findings and pathologic reports of these patients were retrospectively reviewed. US features based on the Korean Thyroid Imaging Reporting and Data System, preoperative US suspicion for lymph node metastasis, and the presence of capsular location were evaluated. Results Univariable and multivariable analyses identified that TCVPTC showed more frequent irregular tumor margin (odds ratio [OR], 6.62; 95% confidence interval [CI], 1.46 to 30.09; P=0.014) and capsular location (OR, 4.63; 95% CI, 1.49 to 14.41; P=0.008) than classic PTC. Capsular location was an independent predictor of TCVPTC for tumors less than or equal to 1.5 cm in size (OR, 4.23; 95% CI, 1.12 to 15.92; P=0.033). Irregular margin was an independent predictor of TCVPTC for tumors larger than 1.5 cm (OR, 10.46; 95% CI, 1.16 to 94.48; P=0.037). Extrathyroidal extension was not significantly different between the two groups. Conclusion The two key features of TCVPTC on US are frequent capsular location for tumors less than or equal to 1.5 cm in size and the higher likelihood of an irregular margin for tumors larger than 1.5 cm.

Purpose This study compared the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS) for thyroid malignancy with three international guidelines. Methods From June to September 2015, 5,708 thyroid nodules (≥1.0 cm) in 5,081 consecutive patients who underwent thyroid ultrasound (US) at 26 institutions were evaluated. The US features of the thyroid nodules were retrospectively reviewed and classified according to all four guidelines. In the modified K-TIRADS, the biopsy size threshold was changed to 2.0 cm for K-TIRADS 3 and 1.0 or 1.5 cm for K-TIRADS 4 (K-TIRADS1.0cm and K-TIRADS1.5cm, respectively). We compared the diagnostic performance and unnecessary fine-needle aspiration biopsy (FNAB) rates for thyroid malignancy between the modified K-TIRADS and three international guidelines. Results Of the 5,708 thyroid nodules, 4,597 (80.5%) were benign and 1,111 (19.5%) were malignant. The overall sensitivity was highest for the modified K-TIRADS1.0cm (91.0%), followed by the European (EU)-TIRADS (84.6%), American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME) (80.5%), American College of Radiology (ACR)-TIRADS (76.1%), and modified K-TIRADS1.5cm (76.1%). For large nodules (>2.0 cm), the sensitivity increased to 98.0% in both the modified K-TIRADS1.0cm and K-TIRADS1.5cm. For small nodules (≤2.0 cm), the unnecessary FNAB rate was lowest with the modified K-TIRADS1.5cm (17.6%), followed by the ACR-TIRADS (18.6%), AACE/ACE/AME (19.3%), EU-TIRADS (28.1%), and modified K-TIRADS1.0cm (31.2%). Conclusion The modified K-TIRADS1.5cm can reduce the unnecessary FNAB rate for small nodules (1.0-2.0 cm), while maintaining high sensitivity for detecting malignancies >2.0 cm.

Purpose This study was conducted to evaluate the diagnostic performance of machine learning in differentiating follicular adenoma from carcinoma using preoperative ultrasonography (US). Methods In this retrospective study, preoperative US images of 348 nodules from 340 patients were collected from two tertiary referral hospitals. Two experienced radiologists independently reviewed each image and categorized the nodules according to the 2015 American Thyroid Association guideline. Categorization of a nodule as highly suspicious was considered a positive diagnosis for malignancy. The nodules were manually segmented, and 96 radiomic features were extracted from each region of interest. Ten significant features were selected and used as final input variables in our in-house developed classifier models based on an artificial neural network (ANN) and support vector machine (SVM). The diagnostic performance of radiologists and both classifier models was calculated and compared. Results In total, 252 nodules from 245 patients were confirmed as follicular adenoma and 96 nodules from 95 patients were diagnosed as follicular carcinoma. As measures of diagnostic performance, the average sensitivity, specificity, and accuracy of the two experienced radiologists in discriminating follicular adenoma from carcinoma on preoperative US images were 24.0%, 84.0%, and 64.8%, respectively. The sensitivity, specificity, and accuracy of the ANN and SVM-based models were 32.3%, 90.1%, and 74.1% and 41.7%, 79.4%, and 69.0%, respectively. The kappa value of the two radiologists was 0.076, corresponding to slight agreement. Conclusion Machine learning-based classifier models may aid in discriminating follicular adenoma from carcinoma using preoperative US.

Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

Purpose: The goal of this study was to investigate the level of agreement between tumor sizes measured on ultrasonography (US) and in pathological specimens of papillary thyroid carcinomas (PTCs) and to identify the US characteristics contributing to discrepancies in these measurements. Methods: We retrospectively reviewed the US findings and pathological reports of 490 tumors in 431 patients who underwent surgery for PTC. Agreement was defined as a difference of

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70–80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

Purpose: The aim of this study was to compare ultrasonographic features in patients with lymphocytic thyroiditis (LT) and papillary thyroid carcinoma (PTC) having suspicious thyroid nodule(s) in a background of heterogeneous parenchyma and to determine the clinical and radiological predictors of malignancy. Methods: We reviewed the cases of 100 patients who underwent ultrasonography between April 2011 and October 2012, and showed suspicious thyroid nodule(s) in a background of heterogeneous parenchyma. Eight patients who did not undergo ultrasonography-guided fineneedle aspiration cytology (FNAC) and 34 cases of follow-up ultrasonography after initial FNAC were excluded. We compared the benign and malignant nodules in terms of their clinical and radiological factors. Results: For the 58 nodules including 31 LTs (53.4%) and 27 PTCs (46.6%), the mean tumor sizes of the two groups were 0.96 cm for LT and 0.97 cm for PTC. A univariate analysis revealed that PTCs were more frequent in patients younger than 45 years and having microcalcifications than was LT. An independent predictor of PTC after adjustment was an age of

Purpose: We aimed to evaluate the efficacy and safety of vigorous saline injection for viscous cystic thyroid nodules. Methods: Eighteen patients who underwent ultrasound-guided aspiration for viscous cystic thyroid nodules using a saline injection were included in our study. After failing to aspirate the cyst by the usual method, we vigorously injected saline into the cyst in multiple directions to break up and liquefy the viscous cystic contents to enable aspiration. The initial and the residual volume of the nodule were calculated, and the volume reduction rate and the time taken to perform the aspiration were recorded. Results: The mean volume of the cystic nodules before aspiration was 11.0 mL (range, 1.2 to 26.0 mL), while the postaspiration volume was 4.2 mL (range, 0.2 to 14.5 mL). The mean aspirated volume was 63.7% of the initial volume. The mean procedure time was 12.4 minutes (range, 5 to 26 minutes). There were no significant complications related to the procedure. Conclusion: A vigorous saline injection followed by aspiration can be a useful method to aspirate viscous cystic thyroid nodules as a prestep for further intervention or simple management..

We aimed to evaluate the diagnostic performance of thyroid ultrasonography (US) in each category of the Bethesda system and analyze false positive/negative findings using US. This retrospective study included 622 thyroid nodules in 592 patients. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of US in each category of the Bethesda system were evaluated. False positive/negative cases of US were analyzed. Out of the 622 total thyroid FNAs, 179 (28.8%) were malignant. The malignancy rates for the 6 categories were as follows: I (nondiagnostic): 9.7%, II (benign): 2.5%, III (atypia/follicular lesion of undetermined significance): 37.5%, IV (suspicious for follicular neoplasm): 5.7%, V (suspicious for malignancy): 100%, and VI (malignancy): 100%. The accuracies of US for the 6 categories were 92.5%, 95.6%, 70.8%, 94.3%, 95%, and 92.4% in category order. US showed the lowest sensitivity (50%) in Category IV. Category III demonstrated relatively low sensitivity (66.7%) and specificity (73.3%) due to a high incidence of follicular variant of papillary thyroid carcinoma and a low number of category III nodules. The most optimal performance of US was revealed in Category I with 88.9% sensitivity and 92.9% specificity. In 22 US false positive cases, the most frequent finding was associated with marked hypoechogenicity and the least finding was noncircumscribed margin. The most common US features of 19 false negative cases were circumscribed iso or hypoechoic nodules. These results highlight the excellent diagnostic performance of US in category I of the Bethesda system and the lowest sensitivity of US in category IV. Awareness of US interpreters regarding these pitfalls can minimize false positive/negative diagnoses and prevent unnecessary interventions.

OBJECTIVE: In this multicenter study, we investigated the management algorithm for thyroid nodules with benign cytology using US features from data collected from 7 institutions. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Data on 700 focal thyroid nodules in 673 consecutive patients were collected from 7 university-affiliated hospitals. This study included nodules that were diagnosed as benign at initial cytologic evaluation and that underwent pathologic or follow-up study. The risk of malignancy was compared according to the US assessments of each institution as well as looking at all the nodules together as a whole. RESULTS: Of the 700 nodules, 688 (98.3%) were benign and 12 (1.7%) were malignant. If initial cytologic results were benign, the likelihood of the nodule actually being malignant was from 1 to 3%, varying by institution. The likelihood of a cytologically benign nodule with positive US being malignant (4.7%, 8/169) was higher than that of one without positive US (0.8%, 4/531) (P = .002). CONCLUSION: Based on our multicenter study, repeat FNA should be performed in thyroid nodules with initial benign cytology showing suspicious US features in order to decrease the number of false negative cases.

We previously reported that high thyroid-stimulating hormone (TSH) levels are associated with papillary thyroid microcarcinoma (PTMC) progression during active surveillance. However, validation with multicenter, long-term data, and identification of appropriate age or TSH levels are needed. This multicenter retrospective study enrolled PTMC patients under active surveillance with TSH measurements and ultrasonography. The primary outcome was PTMC progression (volume increase ≥50%, size increase ≥3 mm, or new lymph node (LN) metastasis). PTMC progression according to time-weighted average of TSH (TW-TSH) groups was compared using survival analyses in overall patients and each age subgroups (<40, 40-49, 50-59, and ≥60 years). The identification of TW-TSH cutoff point for PTMC progression and trend analysis of PTMC pro gression rate according to LT4 treatment were also performed. During 1061 person-years of follow-up, 93 of 234 patients (39.7%) showed PTMC progression (90, 17, and 5 patients for volume increase ≥50%, size increase ≥3 mm, and new LN metastasis, respectively). The highest TW-TSH group was the risk factor most strongly associated with PTMC pr ogression (hazard ratio 2.13 (1.24-3.65); P = 0.006), but the impact was significant only in patients aged <4 0 or 40-49 years (hazard ratio 30.79 (2.90-326.49; P = 0.004), 2.55 (1.00-6.47; P = 0.049)). For patients aged <50 years, TW-TSH cutoff for PTMC progression was 1.74 mU/L, and PTMC progression rates successively increased in the order of effective, no, and ineffective LT4 treatment group (P for trend = 0.034). In young PTMC patients (<50 years), sustained lownormal TSH levels during active surveillance might be helpful to prevent progression. [ABSTRACT FROM AUTHOR]

Background: Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. Methods: From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (KTIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. Results: Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) IFVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iEFVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups ( p = 0.507). Conclusions: Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines. [ABSTRACT FROM AUTHOR]

PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer. [ABSTRACT FROM AUTHOR]