Predictive value of serum HIF-1α/HIF-2α and YKL-40 levels for vascular invasion and prognosis of follicular thyroid cancer.

OBJECTIVE: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). METHODS: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. RESULTS: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. CONCLUSION: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.

Differentiated Thyroid Carcinoma Long-Term Prognostic Factors.

Introduction: Thyroid cancer is the most common cancer in women in Ecuador. Objective: The aim of this study was to determine the demographics and clinical and treatment variables of patients with papillary or follicular thyroid cancer, referred to as differentiated thyroid cancer (DTC), treated at a third-level hospital in Quito, Ecuador. Methods: We reviewed retrospectively the medical records of patients with DTC, who underwent surgical treatment, from 1990 to 2019. Data included demographics, pathological information, clinical stage, type of surgery, and radioactive iodine (RAI) adjuvant therapy. Patients were monitored for up to 29 years (median follow-up time 6.9 years). Results: The corrected overall 5-, 10-, 20-, and 30-year survival rates (Kaplan-Meier) were 93%, 85%, 70%, and 63%, respectively. On univariate analysis, age, histological type, tumor grade, histological variants, capsular invasion, vascular invasion, tumor size, clinical stage, distant metastases at diagnosis, surgical margins, extrathyroidal invasion, radioactive iodine adjuvant treatment, and locoregional recurrence were found to be significant prognostic factors. In a multivariate analysis, the following independent variables: age over 55 years, extrathyroidal spread, metastasis at diagnosis, and stage II to IV raised the risk of death (hazard risk) (HR). Conclusions: Age over 55 years, extrathyroidal spread, metastasis at diagnosis, and advanced clinical stage were found to have a harmful prognosis and an increased risk of death in a series of Ecuadorian patients surgically treated for a DTC.

Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study.

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Clinical Outcomes and Implications of Radioactive Iodine Therapy on Cancer-specific Survival in WHO Classification of FTC.

BACKGROUND: The clinical outcomes and implications of radioactive iodine therapy (RAIT) on cancer-specific survival (CSS) in World Health Organization classification of follicular thyroid carcinoma (FTC) are not well established. MATERIAL AND METHODS: The data of eligible patients with minimally invasive FTC (mi-FTC), encapsulated angioinvasive FTC (ea-FTC), or widely invasive FTC (wi-FTC) between 2000 and 2020 were extracted from the Surveillance, Epidemiology, and End Results database. CSS, the primary outcome, was compared among the 3 subtypes of patients with FTC before and after adjusting for differences using propensity score matching (PSM). The patients with FTC in different subtypes were then divided into 2 groups: the RAIT group and the no-RAIT group. Cox proportional hazards regression analyses were applied to discover the relationships of factors associated with CSS in the each PSM cohort. RESULTS: A total of 2433 patients with mi-FTC, 216 patients with ea-FTC, and 554 patients with wi-FTC were enrolled in the original cohorts, respectively. Patients with mi-FTC or ea-FTC had similar CSS (P = .805), which was better than that of patients with wi-FTC (P < .001; P = .021). Cox proportional hazards regression analysis revealed that RAIT was not associated with improved CSS in either the mi-FTC PSM cohort (hazard ratio [HR], 1.21; 95% CI, .46-3.18; P = .705) or the wi-FTC PSM cohort (HR, 0.56; 95% CI, .35-1.08; P = .086). However, subgroup analysis demonstrated that patients with wi-FTC and N1 stage (HR, 0.44; 95% CI, .20-.99; P = .018) or M1 stage (HR, 0.25; 95% CI, .11-.53; P < .001) could gain CSS advantage from RAIT. CONCLUSION: The RAIT can provide a CSS advantage for patients with wi-FTC who with N1-stage or M1-stage disease.

Primary cell cultures for the personalized therapy in aggressive thyroid cancer of follicular origin.

Thyroid cancer (TC) is the most prevalent endocrine malignancy. More than 90 % of TC is represented by differentiated TC (DTC) arising from the follicular thyroid cells. DTC includes papillary TC (PTC), follicular TC (FTC), and Hürthle cell TC. Anaplastic TC (ATC) accounts for 1% of TC, and it represents 15-40 % of TC death. Current treatment strategies are not completely effective against aggressive DTC or ATC, and mortality is one of the most important challenges. Recently, progresses have been obtained in the understanding of the molecular/genetic basis of TC progression, and new drugs have been introduced [i.e. tyrosine kinase inhibitors (TKIs)], able to block the oncogenic or signaling kinases, associated with cellular growth. Thyroid cell lines, obtained from tumoral cells and chosen for high proliferation in vitro, have been used as preclinical models. Actually, these cells lose the characteristic features of the primary tumor, because they adapt to in vitro growth conditions. For these reasons, the use of these cell lines has important limitations, and more recently human primary cell cultures have been established as monolayer cultures, and investigated for their biological behavior. Moreover, in the past, primary TC cells could be collected only through surgical biopsies, while recently human primary cell cultures can be established also from samples of fine-needle aspiration citology from aggressive dedifferentiated DTC or ATC. Testing in vitro different TKIs in each patient can help to develop new personalized treatments, without using ineffective drugs. In conclusion, personalized medicine and precise oncology, which consider both patients and their disease features, represent the future of the treatment approach, and further progress is needed in this direction.

Avidity and Outcomes of Radioiodine Therapy for Distant Metastasis of Distinct Types of Differentiated Thyroid Cancer.

CONTEXT: The recommendations for radioactive-iodine treatment (RAIT) in metastatic differentiated thyroid cancer (DTC) are mostly based in the experience with papillary histotype and do not consider the differences within the distinct types of DTC, in terms of RAIT uptake and response. OBJECTIVE: This work aims to investigate the association between histology and RAIT avidity and response, and to evaluate whether histotype was an independent prognostic factor in progression-free survival (PFS) and disease-specific survival (DSS) after RAIT for distant metastatic disease. METHODS: A retrospective analysis was conducted of all DTC patients who underwent RAIT for distant metastatic disease, from 2001 to 2018, at a thyroid cancer referral center. We included 126 patients: 42 (33.3%) classical variant papillary thyroid cancer (cvPTC), 45 (35.7%) follicular variant PTC (fvPTC), 17 (13.5%) follicular thyroid cancer (FTC) and 22 (17.5%) Hürthle cell carcinoma. Main outcome measures included RAIT avidity and response. RESULTS: RAIT avidity was independently associated with histology (P < .001) and stimulated thyroglobulin (Tg) at first RAIT for distant lesions (P = .007). Avidity was lowest in HCC (13.6%), intermediate in cvPTC (21.4%), and highest in fvPTC (75.6%) and FTC (76.5%). Regarding RAIT response, HCC and FTC were not different; both showed significantly more often progression after RAIT than fvPTC and cvPTC. Histology influenced PFS (P = .014), but tumor type was not a significant prognostic factor in DSS. Instead, age at diagnosis, resection status, and stimulated Tg at the first RAIT were significantly associated with DSS. CONCLUSION: DTC histotype influenced RAIT avidity and PFS. It is crucial to better detect the metastatic patients that may benefit the most from RAIT.

[18F]-FDG-PET/CT Correlates With the Response of Radiorefractory Thyroid Cancer to Lenvatinib and Patient Survival.

CONTEXT: 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography ([18F]-FDG-PET/CT)-positive metastatic lesions in radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) have a poor prognosis and lenvatinib represents the best therapy. OBJECTIVE: We investigated the role of [18F]-FDG-PET/CT in the evaluation of metabolic response and prediction of the outcome of RAI-R DTC patients treated with lenvatinib. METHODS: Patients (n = 33) with progressive metastatic RAI-R DTC who were treated with lenvatinib were investigated at baseline and during follow-up with biochemical (thyroglobulin and thyroglobulin antibodies), morphological (whole-body CT scan) and metabolic ([18F]-FDG-PET/CT) evaluation. RESULTS: Nineteen (57.6%) patients showed the greatest metabolic response at the first [18F]-FDG-PET/CT scan, performed after 4 weeks of lenvatinib, while 5/33 (15.1%) patients had this response later. Moreover, 66.7% of patients had both a metabolic response at the first [18F]-FDG-PET/CT scan and a morphological response at the first CT scan. We observed a correlation between the metabolic response at [18F]-FDG-PET/CT scan performed after 4 weeks of treatment and the biochemical response at the same time in 60.6% of patients. The median overall survival (OS) was significantly longer in patients with either a metabolic response at last [18F]-FDG-PET/CT (40.00 vs 8.98 months) or a morphological response at last CT scan (37.22 vs 9.53 months) than in those without response. Moreover, the OS was longer in patients with a metabolic response at [18F]-FDG-PET/CT performed after 4 weeks of treatment (36.53 vs 11.28 months). CONCLUSIONS: Our data show that [18F]-FDG-PET/CT can early predict the response to lenvatinib and correlates with the OS of RAI-R DTC patients treated with this drug.

Pregnancy Does not Affect the Prognoses of Differentiated Thyroid Cancer Patients With Lung Metastases.

CONTEXT: Pregnancy-related hormones may stimulate thyroid cancer growth, but whether pregnancy affects the prognoses of patients with lung metastases from differentiated thyroid cancer (DTC-LM) after surgery and radioiodine therapy is unclear. OBJECTIVE: To assess the impact of pregnancy on DTC-LM through the comparison of prognoses between female patients with DTC-LM who did and did not become pregnant after surgery and radioiodine therapy. METHODS: We retrospectively analyzed the records of 124 female patients aged 16 to 35 years who underwent surgery and radioiodine therapy for DTC-LM. These patients were divided into pregnancy group (n = 37) and nonpregnancy group (n = 87) according to whether they became pregnant after surgery and radioiodine therapy, regardless of whether they had a pregnant history before treatment. RESULTS: The 5- and 10-year progression-free survival rates were 94.52% and 63.22% in pregnancy group versus 89.82% and 58.13% in nonpregnancy group. The 5- and 10-year cumulative overall survival rates of pregnancy group were 97.30% and 85.77% versus 93.50% and 81.95% in nonpregnancy group (all P > 0.05). The median time of follow-up in the pregnancy and nonpregnancy groups was 82 months (25-136 months) and 68 months (13-133 months), respectively. Non-radioiodine-avid LM and primary tumors needing repeated resection were independent predictors of poor progression-free survival for patients in pregnancy group. CONCLUSION: Pregnancy does not affect the prognoses of patients with DTC-LM after surgery and radioiodine therapy. Non-radioiodine-avid LM and repeated primary tumor surgeries are independent risk factors for poor prognoses of pregnant patients.

Clinical Implication of World Health Organization Classification in Patients with Follicular Thyroid Carcinoma in South Korea: A Multicenter Cohort Study.

BACKGROUND: The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC). METHODS: This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell's C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS. CONCLUSION: WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

The Oncocytic Variant of Poorly Differentiated Thyroid Carcinoma Shows a Specific Immune-Related Gene Expression Profile.

BACKGROUND: Poorly differentiated thyroid cancer (PDTC) is a rare, follicular cell-derived neoplasm with an unfavorable prognosis. The oncocytic variant of PDTC may be associated with even more adverse outcome than classical PDTC cases, but its specific molecular features are largely unknown. Our aim was to explore the immune-related gene expression profile of oncocytic and classical PDTC, in correlation with clinical and pathological characteristics (including programmed death ligand 1 [PD-L1] expression) and outcome, and in comparison with a control group of well-differentiated follicular carcinomas (WDFCs), including conventional follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). METHODS: A retrospective series of 48 PDTCs and 24 WDFCs was analyzed by means of NanoString technology employing the nCounter PanCancer Immune Profiling panel. Gene expression data were validated using quantitative real-time polymerase chain reaction. RESULTS: Oncocytic PDTCs showed a specific immune-related gene expression profile, with higher expression of LAIR2, CD274, DEFB1, IRAK1, CAMP, LCN2, LY96, and APOE, and lower expression of NOD1, as compared to conventional PDTCs. This molecular signature was associated with increased intratumoral lymphocytic infiltration, PD-L1 expression, and adverse outcome. Three of these genes, CD274, DEFB1, and IRAK1, as well as PD-L1 expression, were also the hallmarks of HCCs as compared to FTCs. By contrast, the panel of genes differentially regulated in PDTCs as compared to WDFCs was unrelated to the oncocytic phenotype. CONCLUSIONS: Our results revealed a distinctive immune-related gene expression profile of oncocytic PDTC and confirmed a more aggressive outcome in this cancer subtype. These findings may provide guidance when exploring novel immunotherapeutic options for oncocytic PDTC patients.

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database.

OBJECTIVES: In this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer. MATERIALS AND METHODS: Cox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate. RESULTS: A total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4-2.3, p < 0.001; HR = 1.9, 95% CI: 1.6-2.3, p < 0.001; HR = 1.4, 95% CI: 1.0-1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2-1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3-1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9-1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects. CONCLUSION: Patients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.

Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma.

The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04-2.56, p = 0.03, I2 68%, τ2 0.19 and HR 1.90, CI 1.33-2.70, p< 0.001, I2 0%, τ2 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.

BRAF and TERT promoter mutations: clinical application in thyroid cancer.

Given the long-term survival of most patients with thyroid cancer, it is very important to distinguish patients who need aggressive treatment from those who do not. Conventional clinicopathological prognostic parameters could not completely predict the final outcome of each patient. Recently, molecular marker-based risk stratification of thyroid cancer has been proposed to better estimate the cancer risk. Although BRAF mutation has drawn much attention based on its high prevalence, its association with recurrence or mortality is not clear. Recently, telomerase reverse transcriptase (TERT) promoter mutation has been identified in thyroid cancer. It increases telomerase activity, which allows cancer cells to immortalize. It was found in 10 to 20% of differentiated thyroid carcinoma and 40% of dedifferentiated thyroid carcinoma. It is highly prevalent in old age, large tumor, aggressive histology, advanced stages, and distant metastasis. It is associated with increased recurrence and mortality. Concomitant BRAF and TERT promoter mutations worsen the survival rate. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.

Efficacy and Limitations of Lenvatinib Therapy for Radioiodine-Refractory Differentiated Thyroid Cancer: Real-World Experiences.

Background: The ultimate clinical goal of advanced cancer treatment is improvement of survival. Tyrosine kinase inhibitors (TKIs) were recently approved for radioiodine-refractory differentiated thyroid carcinoma (RR-DTC) that is resistant to conventional therapies since they have significant potential to improve survival in patients who previously had no more treatment strategies available. However, eligible patients are limited in clinical practice, making it difficult to accurately determine the efficacy of TKIs. Patients and Methods: We retrospectively analyzed the efficacy of lenvatinib at a single institution, enrolling 42 RR-DTC patients. Results: The best overall response was partial remission in 26 (62%) patients, stable disease in 10 (24%) patients, and progressive disease (PD) in 6 (14%) patients. The results indicated three-year overall survival (OS) and progression-free survival rates of 51.0% and 32.4%, respectively. Twenty-three (55%) patients had backgrounds that did not match the inclusion criteria of the Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial. Furthermore, PD-experienced patients individually decided whether to continue lenvatinib, and 17 (41%) made the decision themselves; these patients had a three-year OS of 43.0% and postprogression survival (PPS) of 13.3 [95% confidence interval 6.1-not reached] months. Conclusions: Our real-world investigation revealed that patients have wide-ranging background characteristics, and the decision regarding continuation of therapy after PD is based on the patient's general condition. Our management protocol resulted in good PPS. Furthermore, our results indicated equivalent efficacy of lenvatinib as in the SELECT trial. In conclusion, lenvatinib proved effective for RR-DTC patients in a real-world setting.

Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up.

Objective: The objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up. Methods: A retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019. Results: In total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively). Conclusions: WDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.

Expression of long non-coding RNA H19 predicts distant metastasis in minimally invasive follicular thyroid carcinoma.

Downregulation of lncRNA H19 (H19) expression is associated with an unfavorable prognosis in some cancers. However, little was known as to whether there was an association between H19 and minimally invasive follicular thyroid carcinoma (MI-FTC). In our study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to determine H19 expression in 186 patients with MI-FTC who underwent initial surgery. Of the 186 patients with MI-FTC, 21 patients show distant metastasis （M+）at the initial operation established the diagnosis of MI-FTC. Of the 165 patients who did not show distant metastasis at diagnosis during the follow-up period (≥10 years), 28 patients undergone M+ and 137 patients has no distant metastasis（M-）after the initial operation. Low H19 expression was associated with large tumor size, vascular invasion, and distant metastasis. Univariate analysis showed that gender (male), age (45 years or older), primary tumor size (4 cm or more), vascular invasion and H19 level (<1.12) were significant prognostic factors related to postoperative distant metastases. Multivariate analysis showed that age, primary tumor size (4 cm or more) and vascular invasion was a significant prognostic factor for survival. Patients with low H19 expression showed a poorer outcome in MI-FTC patients. Receiver-operating characteristic (ROC) curve analysis demonstrated H19 could distinguish M+ from M- patientswith a value of area under the curve (AUC). Our findings suggest that H19 is a potential prognostic factor for evaluating prognosis and the metastatic potential of MI-FTC at an initial operation stage.

Cytologic features of aggressive variants of follicular-derived thyroid carcinoma.

Certain carcinomas of the thyroid gland behave aggressively resulting in increased patient morbidity and poor patient prognosis. The diagnosis of these aggressive thyroid cancer subtypes is sometimes challenging and subject to increased interobserver variability. This review deals with the cytological features of such tumors including aggressive variants of papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. These malignancies fall into 2 groups based on their cytomorphology: those that exhibit distinct microscopic features (eg, nuclear findings typical of classical papillary thyroid carcinoma or marked anaplasia) and those that present with more subtle cytologic features (eg, nuclear pseudostratification, "soap bubble" nuclei, supranuclear or subnuclear cytoplasmic vacuoles, rosette-like structures, hobnail cells). We review the literature regarding these aggressive thyroid cancers and highlight important phenotypic characteristics that can be useful for their diagnosis based on fine needle aspiration.

Risk of death due to disease for thyroid fine-needle aspirations of well-differentiated thyroid carcinomas.

The risk of malignancy for some diagnoses in thyroid fine-needle aspirations is higher than the actual risk of clinical progression. Other measures of prognosis may be helpful in managing patients with indeterminate thyroid fine-needle aspiration diagnoses. We estimated the risk of death due to disease (RDDD) for well-differentiated thyroid carcinoma using a series of over 15 000 aspirates with over 2000 excisions and data from the SEER database. RDDD was low (1.3% or less for all categories). The RDDD of some indeterminate thyroid aspirates was higher than for malignant aspirates. The RDDD may provide additional information for patients and clinicians seeking to manage patients with indeterminate thyroid fine-needle aspirates.

Evaluating the 2015 American Thyroid Association Risk Stratification System in High-Risk Papillary and Follicular Thyroid Cancer Patients.

Background: The 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Earlier studies evaluating this system evaluated the 2009 edition, comprised a low number of patients with ATA high-risk, had low numbers of patients with follicular thyroid cancer (FTC), or did not distinguish between papillary and FTC. Therefore, we evaluated the prognostic value of the 2015 ATA Risk Stratification System in a large population of high-risk thyroid cancer patients, which included a substantial proportion of FTC patients. Methods: We retrospectively studied adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and December 2015. All patients fulfilled the 2015 ATA high-risk criteria. Overall survival and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method. Logistic regression and Cox proportional hazards models were used to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as survival. Results: We included 236 patients with high-risk DTC (32% FTC) with a mean age of 56 years. Median follow-up was 6 years. At final follow-up, 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All high-risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up. During follow-up, 14% of the 79 patients who achieved excellent response developed a recurrence. Finally, 10-year DSS was much higher in the initial excellent response than in the initial structural disease group (100% vs. 61%, respectively). Conclusions: In a population of high-risk DTC patients harboring a large subset of FTC patients, the 2015 ATA Risk Stratification System is not only an excellent predictor of persisting disease but also of survival. As much as 14% of the high-risk patients who had an excellent response upon dynamic risk stratification experienced a recurrence during follow-up. Clinicians should thus be aware of the relatively high recurrence risk in these patients, even after an excellent response to therapy.

Surgical Management and Factors Affecting the Prognosis for Patients with Thyroid Cancer Spinal Metastases: A Retrospective Analysis of 52 Consecutive Patients from a Single Center.

BACKGROUND: Thyroid cancer, one of the most common endocrine malignancies in developed areas and China, is associated with favorable prognosis. However, the presence of spinal metastases will remarkably reduce the life expectancy for patients with thyroid cancer. In addition, limited information is available about such disease. METHODS: Various potential clinical factors were submitted to univariate and multivariate analyses to identify the independent variables that predicted the prognosis for patients. In addition, the survival rate was estimated according to the Kaplan-Meier method, and statistic differences were calculated by the log-rank test. Moreover, factors with a P value of ≤0.1 were performed multivariate analysis using a multivariate Cox proportional hazards model, and factors with a P value of <0.05 were considered as statistically significant. RESULTS: Seven potential independent prognostic factors had been identified through univariate analysis, which were then subjected to multivariate analysis. Our results suggested that age of ≤50 years, single segment involved, and follicular thyroid cancer were the independent favorable prognostic factors. CONCLUSIONS: Findings in this study indicate that age of ≤50 years, single segment involved, and follicular thyroid cancer are favorable prognostic factors for patients with thyroid cancer spinal metastases.