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Background: Research has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causality of circulating lipoprotein lipids on DTC. Methods: Mendelian randomization (MR) analysis was conducted to evaluate the relationship between the circulating lipoprotein lipids and DTC risk using singlenucleotide polymorphisms (SNPs) from a genome-wide association (GWA) study containing a high-incidence Italian population of 690 cases samples with DTC and 497 controls. Results: Univariate and multivariate mendelian randomization analysis demonstrated that 'total cholesterol', 'HDL cholesterol', 'apolipoprotein B' and 'ratio of apolipoprotein B to apolipoprotein A1' were correlated with DTC. According to sensitivity analysis, our results were reliable. Furthermore, multivariate analysis revealed that there is no causative association between DTC and any of the many cause factors when they interact with one another, suggesting that there was a deep interaction between the four factors, which could affect each other. Finally, the mechanism of the related effects each other as well as the target genes with significant SNP regulatory effects in DTC was explored by conducting functional enrichment analysis and constructing the regulatory networks. Conclusions: We obtained four exposure factors (total cholesterol, HDL cholesterol, apolipoprotein B and ratio of apolipoprotein B to apolipoprotein A1) closely related to DTC, which laid a theoretical foundation for the treatment of DTC. [ABSTRACT FROM AUTHOR]

Background: Radioiodine (131I) therapy (RAIT) is associated with oxidative stress (OS)-induced DNA damage in patients with differentiated thyroid cancer (DTC). The goal of this study was to evaluate the possible ameliorating effects of Panax Ginseng (PG) on RAIT-induced genotoxicity in patients with DTC. Materials and Methods: Forty DTC patients who had received 131I (100 to 175 mCi) were enrolled in this study. The patients were randomly classified (n = 10) into control, placebo, PG1 groups (receiving 500 mg/day of PG for 2 days before RAIT), and PG2 group (receiving 500 mg/day of PG for 2 days before to 1 day after RAIT). Blood samples were collected before and 2 days after RAIT. Lymphocyte micronuclei (MN) frequency was measured using the MN assay. Serum total antioxidant capacity (TAC) and ischemia-modified albumin (IMA) were measured using colorimetric assays. Serum albumin, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using commercial kits. Results: The mean of baseline MN frequency was the same in the four groups. RAIT increased the MN frequencies to at least three times the baseline values in the control (39 ± 5) and placebo groups (38 ± 6) (P < 0.001). PG caused a significant decrease in the MN frequencies in the treated groups compared to the control and placebo groups (P < 0.001). RAIT and PG administration had no significant effects on the serum IMA, TAC, and markers of liver and kidney toxicity. Conclusion: PG could be considered a useful remedy for the protection against RAIT-induced chromosomal damage in DCT patients. KEY WORDS: Differentiated thyroid cancer, genotoxicity, Panax ginseng, radioiodine therapyBackground: Radioiodine (131I) therapy (RAIT) is associated with oxidative stress (OS)-induced DNA damage in patients with differentiated thyroid cancer (DTC). The goal of this study was to evaluate the possible ameliorating effects of Panax Ginseng (PG) on RAIT-induced genotoxicity in patients with DTC. Materials and Methods: Forty DTC patients who had received 131I (100 to 175 mCi) were enrolled in this study. The patients were randomly classified (n = 10) into control, placebo, PG1 groups (receiving 500 mg/day of PG for 2 days before RAIT), and PG2 group (receiving 500 mg/day of PG for 2 days before to 1 day after RAIT). Blood samples were collected before and 2 days after RAIT. Lymphocyte micronuclei (MN) frequency was measured using the MN assay. Serum total antioxidant capacity (TAC) and ischemia-modified albumin (IMA) were measured using colorimetric assays. Serum albumin, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured using commercial kits. Results: The mean of baseline MN frequency was the same in the four groups. RAIT increased the MN frequencies to at least three times the baseline values in the control (39 ± 5) and placebo groups (38 ± 6) (P < 0.001). PG caused a significant decrease in the MN frequencies in the treated groups compared to the control and placebo groups (P < 0.001). RAIT and PG administration had no significant effects on the serum IMA, TAC, and markers of liver and kidney toxicity. Conclusion: PG could be considered a useful remedy for the protection against RAIT-induced chromosomal damage in DCT patients. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 deiodinase (DIO2) enzyme plays a vital role in peripheral T4 to T3 conversion and in the negative feedback regulation of pituitary thyroid-stimulating hormone (TSH) secretion. Thr92Ala polymorphism (rs225014) is a common single-nucleotide polymorphism (SNP) that lowers DIO2 activity and is associated with diverse physiological disorders. Differentiated thyroid cancer (DTC) patients are given L-T4 therapy after total thyroidectomy and 131I treatment to suppress TSH levels. Aim: The aim of the study was to determine the frequency of rs225014 in DTC patients and to investigate its effect on the thyroid function tests (TFTs) and L‑T4 dose required to suppress TSH levels. Materials and Methods: The study included a DTC patient group and a control group. TFTs were estimated by RIA/IRMA kits. Genomic DNA of all the subjects was screened for rs225014 SNP by polymerase chain reaction. Results: The frequency of Thr/Thr (wild type), Thr/Ala (heterozygous mutant), and Ala/Ala (homozygous mutant) genotypes in the DTC patients’ group was 0.21, 0.52, and 0.27, respectively. T3 levels and T3/T4 ratio were significantly low in the Ala/Ala genotype in the DTC group indicating impaired DIO2 activity. L-T4 dose requirement to suppress TSH levels in the DTC patients harboring rs225014 SNP was not statistically different from the wild-type genotype. Conclusion: The SNP rs225014 was observed to be associated with T3 and T3/T4 ratio but not with the L-T4 dose in DTC harboring SNP suggesting the presence of a compensatory pathway to overcome DIO2 impairment. However, it is essential to study the genetic makeup of DTC patients showing reduced response to TSH suppression to enable quicker decision‑making in the implementation of personalized L‑T4 dose to prevent any adverse effects. [ABSTRACT FROM AUTHOR]

Patients with differentiated thyroid cancer usually present with early-stage disease and undergo surgery followed by adjuvant radioactive iodine ablation, resulting in excellent clinical outcomes and prognosis. However, a minority of patients relapse with metastatic disease, and eventually develop radioactive iodine refractory disease (RAIR). In the past there were limited and ineffective options for systemic therapy for RAIR, but over the last ten to fifteen years the emergence of tyrosine kinase inhibitors (TKIs) has provided important new avenues of treatment for these patients, that are the focus of this review. Currently, Lenvatinib and Sorafenib, multitargeted TKIs, represent the standard first-line systemic treatment options for RAIR thyroid carcinoma, while Cabozantinib is the standard second-line treatment option. Furthermore, targeted therapies for patients with specific targetable molecular abnormalities include Latrectinib or Entrectinib for patients with NTRK gene fusions and Selpercatinib or Pralsetinib for patients with RET gene fusions. Dabrafenib plus Trametinib currently only have tumor agnostic approval in the USA for patients with BRAF V600E mutations, including thyroid cancer. Redifferentiation therapy is an area of active research, with promising initial results, while immunotherapy studies with checkpoint inhibitors in combination with tyrosine kinase inhibitors are underway. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer usually has a good prognosis; however, recurrence occurs in 5% to 20% of patients after initial treatment, which causes physiopsychological and financial burdens for the patients. In the meantime, it complicates the treatment decision-making for clinicians. Different from initial treatment, the management of recurrent thyroid cancer should take comprehensive consideration of factors such as risks and benefits. Surgery is considered to be the first choice of treatment while radioactive iodine therapy is recommended for radioiodine-avid recurrent disease. Smaller lesions can be managed with active surveillance temporarily, and thermal ablation should only be applied to patients not suitable for additional surgery. In contrast, external beam radiotherapy and systemic therapies are considered only after all therapy options have been exhausted. [ABSTRACT FROM AUTHOR]

Background: Emerging remote-access surgical methods are utilized to treat differentiated thyroid cancer. The study aimed to compare the surgical integrity, safety, efficacy, and postoperative experience of patients among common surgical methods. Methods: The PubMed, Medline, Cochrane Library, Web of Science, and EMBASE databases were searched from their inception until March 2023. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The surface under the cumulative ranking curve (SUCRA) was used to illuminate the probability that each method would be the best for each outcome. Results: Thirty-two studies comprising 7042 patients were included. Robotic bilateral axillo-breast approach (RBABA) and robotic gasless transaxillary approach (RGAA) retrieved fewer lymph nodes (LNs) than open thyroidectomy (OT). RBABA showed a significantly lower permanent recurrent laryngeal nerve (RLN) palsy rate than OT. According to SUCRA values, endoscopic transoral approach (EOA) ranked the highest in retrieved LNs (0.84), the proportion of stimulated serum thyroglobulin less than 1.0 ng/ml (0.77), and the pain score (0.77). Endoscopic bilateral areola approach (EBAA) ranked the highest in the transient RLN palsy rate (0.72). The endoscopic gasless transaxillary approach (EGAA) ranked the highest in the transient hypoparathyroidism rate (0.78). RBABA ranked the highest in the rate of permanent RLN palsy (0.94) and hypoparathyroidism (0.77). OT ranked the highest in operative time (0.92). Conclusions: Each surgical method of total thyroidectomy has benefits and limitations. EOA performed the best in maintaining surgical integrality and reducing the pain score, while taking a long operative time. Generally, RBABA showed the best advantage in protecting parathyroid glands and RLN but with the longest operative time. OT had the best advantage in operative time. Therefore, OT and EOA are ideal methods for patients with a higher risk of central LN metastasis. RBABA and EOA may not be suitable for elderly patients or those with high anesthesia risk. [ABSTRACT FROM AUTHOR]

Objective: Identify and appraise clinical practice guidelines (CPGs) for radioactive iodine (RAI) indications in differentiated thyroid carcinoma (DTC), and the treatment for radioactive iodine refractory (RAI‐R) DTC using the Appraisal of Guidelines for Research and Evaluation II tool. Data Sources: MEDLINE (Pubmed), Ovid (EMBASE), and Scopus. Review Methods: A systematic literature search was conducted to identify CPGs addressing RAI in DTC. CPGs were appraised by 4 independent reviewers in 6 distinct areas of quality. Scaled domain scores were subsequently calculated for each domain. Intraclass correlation coefficients were calculated for each domain to assess interrater reliability. Results: Sixteen guidelines were found addressing RAI indications for DTC. Of these 16, 9 also addressed the treatment of RAI‐R DTC. A further 6 unique guidelines were identified that exclusively address RAI‐R DTC, bringing the total number of guidelines to 22. The American Thyroid Association (ATA) guidelines for adult thyroid cancer were the highest scoring with a mean score of 83.5%. Two guidelines scored >60% in 5 or more domains, qualifying as "high" quality: ATA and British Thyroid Association. The highest scoring domain was domain 4: clarity of presentation (80.4%) while the lowest scoring domain was domain 5: applicability (38.6%). Conclusion: Of the 22 guidelines identified, only two were "high quality." CPGs exclusively addressing the treatment of RAI‐R DTC were weak with most guidelines scoring in the "low" quality range. This report reveals an unmet need for rigorously developed guidelines addressing indications for RAI in DTC, as well as the treatment for RAI‐R DTC. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical features of multifocal differentiated thyroid carcinoma (MDTC)with negative clinicalstage(cN0)and the independent influencing factors of centrallymph node metastasis. Methods The data of 228 patients withc N0 differentiated thyroid cancer(DTC) admitted to the Department of Oncology, the First Affiliated Hospital of Bengbu Medical College from January 2020 to December 2021 were retrospectively analyzed. According to the number of cancerfoci, they were divided into MDTC group(n=78) and single-focal differentiated thyroid cancer(SDTC) group(n=150). The clinical features of MDTC were analyzed bycomparing the differences in gender, age, diameter of cancer foci, number of cancer foci, capsuleinvasion, centrallymph nodemetastasis and Hashimoto'sthyroiditis between the two groups. Logistic regression was selected to analyze the influencing factors of central lymph node metastasis. Results There was significant difference in age, gender and tumor diameter between the SDTC group and the MDTC group (P <0. 05). However, the MDTC group was more likely to invade the thyroid capsule, develop central lymph node metastasis, and have Hashimoto's thyroiditis. There was no significant difference between the two groups (P <0. 05). Compared with patients with two lesions, patients with three or more lesions were more likely to invade the thyroid capsule and have central lymph node metastasis, and the difference was statistically significant( P <0. 05). However, there was no significant differencein Hashimoto's thyroiditis(P >0. 05). Logistic regression analysis showed that the invasion of thyroid capsule and the number of cancer foci were independent influencing factors of cervical central lymph node metastasis(OR=7. 714, 0. 140, P=0. 033, 0. 007). Conclusion Patients with cN0 MDTC have stronginvasiveness, and total thyroidectomy is recommended. [ABSTRACT FROM AUTHOR]

Purpose: The fracture risk assessment tool (FRAX) is used to assess the 10-year risk of major site and hip fractures; however, whether this tool can be applied to patients receiving levothyroxine-based thyroid-stimulating hormone (TSH) suppressive therapy for postoperative differentiated thyroid cancer (DTC) patients is yet to be clarified. Methods and design: A total of 64 patients with DTC following thyroidectomy and oral levothyroxine for TSH suppression therapy and 30 gender- and agematched controls were collected. The fracture risk was compared between the affected groups with different TSH levels. FRAX was used to calculate the fracture risk with and without bone mineral density (BMD). The TSH level was converted to an age-weighted score to estimate the fracture risk of postoperatively differentiated thyroid cancer patients. The sensitivity, specificity, and area under the AUC curve of the traditional FRAX and the new algorithm for osteoporosis diagnosis were compared. The dual-energy X-ray bone mineral density measurement T score was used as the gold standard to diagnose osteoporosis. Results: There were 24 patients in the T ≥ −1–2.5 group, 23 in the −2.5 < T < −1 group, and 17 in the T ≤ −2.5 group. The T score of BMD in the disease group was significantly lower than that in the control group (p < 0.05). The risk of MOF and hip fracture without a T score were significantly different under various TSH levels (p < 0.05). The area under the curve (AUC) of FRAX without BMD for predicting major osteoporotic fractures (PMOF) and major hip fractures (PHF) was 0.694 and 0.683, respectively. The cutoff values were 2.15% and 0.25%, respectively. The AUC of FRAX with BMD for PMOF and PHF was 0.976 and 0.989, respectively, and the cutoff values were 4.15% and 1.1%, respectively. The AUC of FRAX without BMD for PMOF and PHF was 0.708 and 0.72, respectively, and the cutoff values were 5.5% and 1.55%, respectively. Conclusions: FRAX is suitable for postoperative DTC patients after TSH suppressive therapy. In the absence of BMD, TSH weighted by age can improve the specificity of FRAX in the diagnosis of osteoporosis in this population. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its outcome is usually favorable. Its basic treatment is well codified, but its monitoring is much less. The value of thyroglobulin (Tg) is one of the main elements for monitoring DTC, while the use of iodine scintigraphy is becoming less recommended. In this case report, we discuss a clinical situation where a patient presented differentiated thyroid metastatic lesions confirmed by biopsy, uptaking radioactive iodine, with undetectable levels of Tg (in the absence of autoantibodies). We discuss the various hypotheses explaining this clinical situation, the potential advantages of performing periodic iodine scintigraphy in some intermediate and high-risk patients and report the documented clinical benefit of radioiodine therapy. [ABSTRACT FROM AUTHOR]

Objective：This study aims to investigate the effects of intraoperative neuromonitoring (IONM) on postoperative voice outcomes of by differentiated thyroid cancer (DTC) . Methods：We assessed patients with DTC underwent thyroid surgery in the First Affiliated Hospital of Sun Yat⁃sen University from September 2018 to March 2019. According to whether IONM was used or not，the patients were divided into IONM group and non ⁃ IONM group. Clinicopathological characteristics and voice outcomes between IONM and non ⁃ IONM patients with DTC were compared using propensity score matching (PSM) . Results：In the whole population and the subgroup of lymph node dissection in the prevention center，there was no statistical difference between the two groups in the total score of the voice handicap index ⁃ 10 (VHI⁃10) and the voice field of the thyroid cancer specific quality of life (THYCA⁃QoL) questionnaire 1 and 6 months after surgery (P>0.05) . In the subgroup of approaching or invading the posterior capsule，the median (quartile) THYCA⁃ QoL voice score in the IONM group at 1 month and 6 months after surgery was 0.00 (0.00，0.00) lower than in the non⁃IONM group 0.00 (0.00，33.33) ， (P=0.034) . The score of THYCA⁃QoL in the IONM group was 5.73 lower than that in the non⁃IONM group 15.66 (P= 0.029) . There was no statistical difference in the VHI ⁃ 10 questionnaire. Conclusion：IONM has no significant effect on subjective phonation disorder in patients with DTC and subgroup patients with preventive central lymphadenectomy. However，it can significantly improve the subjective voice abnormalities of patients in the approaching or invading the posterior capsule subgroup after surgery. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) in young adults has been steadily rising in incidence over the decades. However, data on long-term outcomes in this specific cohort remain limited. In this study, we intended to evaluate young adults with DTC with regard to their clinical characteristics and treatment outcomes and compare the same vis-à-vis pediatric patients with DTC. Methods: Data of pediatric (≤18 years) and young adult (19-39 years) patients with DTC, from 1971 to 2016, were sequentially extracted and analyzed for clinical characteristics, treatment responses, rates of recurrent/persistent disease, and disease-free survival (DFS). Results: A total of 1803 patients with DTC were included (pediatric cohort: n = 176; young adult cohort: n = 1627). Pediatric patients with DTC had more frequent adverse baseline features including extrathyroidal extension (P = .040), nodal and distant metastases, and American Thyroid Association high-risk disease (P < .001 each). At 2 years posttreatment, young adult patients with DTC had significantly lower incomplete responses compared with pediatric patients with DTC (223/1627; 13.7% vs 94/176, 53.4%, respectively; P< .001). Over a median follow-up of 10.7 years, 120/1627 (7.4%) young adult patients with DTC had recurrent/persistent disease vs 23/176 (13.1 %) pediatric patients with DTC (P = .012). The 10-year DFS probability was 93.6% for the young adult patients with DTC vs 88.7% for the pediatric patients with DTC (P = .007). American Thyroid Association high-risk disease and incomplete response at 2 years were independent predictors of significantly worse DFS in the young adult cohort (P < .001 each). Conclusions: Young adult DTCs behave less aggressively compared with their pediatric counterparts with excellent long-term outcomes. Appropriate initial and dynamic risk stratification can help optimize treatment decisions and follow-up strategies. [ABSTRACT FROM AUTHOR]

Purpose: To study whether male sex is a risk factor for prognosis in patients with differentiated thyroid cancer after 131I treatment using the propensity score matching (PSM) method. Methods: From April 2016 to October 2021, 1948 postoperative differentiated thyroid cancer patients aged 43 (interquartile range: 34, 54) years who received 131I treatment were retrospectively enrolled and divided into male (n = 645) and female groups (n = 1303). The PSM method was adopted to process all data to reduce the influence of data bias and confounding variables. The Mann-Whitney U test and χ² test were used for data analysis. Multivariate logistic regression was used to analyze the risk factors affecting prognosis, and the receiver operating characteristic curve was used to analyze the relationship between stimulated thyroglobulin (sTg) level, 131I dose, and poor prognosis. Results: Before PSM, the proportion of male patients with poor prognosis was significantly higher than that of female patients. After PSM, there was no difference in the proportion of poor prognosis between male and female groups. Multivariate logistic regression analysis showed that male sex; high T stage, N1b stage, and M1 stage; high sTg level; and high 131I dose were risk factors for poor prognosis before PSM. After PSM, high T stage, M1 stage, high sTg level, and 131I dose were still risk factors but male sex was no longer a risk factor for poor prognosis. Conclusions: After the reduction of selection bias by PSM, male sex was no longer a risk factor for prognosis after 131I treatment of differentiated thyroid cancer. In addition, high T stage (T3 + T4 stage), M1 stage, sTg >10.15 ng/mL, and 131I dose ≥260 mCi were risk factors for poor prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Patients with locally advanced or metastatic differentiated thyroid cancer (DTC) have a variable prognosis, and the development of more effective treatment strategies is an important research topic. Overall survival (OS) is the gold standard for research endpoints in randomized controlled trials (RCTs), but observing an OS benefit requires the inclusion of a large number of patients and a long follow-up period. In this study, we aimed to investigate whether progression-free survival (PFS) could be used as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials. Materials and methods: We conducted a search in the PubMed and EMBASE databases to include all RCTs of locally advanced or metastatic DTC and extracted survival data. A weighted linear regression analysis was performed to explore the correlation between PFS benefit and OS benefit by taking the logarithm of the hazard ratios (HRs) of PFS and OS for each trial with a base of 10 and weighted by the number of patients in each RCT. Results: Seven RCTs, including 1410 patients, were included. At the trial level, PFS benefit was weakly correlated with OS benefit (R2 = 0.210, 95% CI: 0.000–0.811) and did not meet the statistical criteria for the surrogate endpoint. Conclusion: This study does not support PFS as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials. Trial registration: PROSPERO Identifier: CRD42022334898 [ABSTRACT FROM AUTHOR]

Despite a growing body of evidence for the effectiveness of prehabilitation, the uptake of prehabilitation in Europe remains low. Contributing factors range from limited awareness and understanding of prehabilitation to a lack of supporting infrastructure and reimbursement challenges. In this position paper, the authors propose a new comprehensive definition of prehabilitation and identify differentiated thyroid cancer as a type of cancer particularly well-suited for prehabilitation. To support clinicians with the implementation of prehabilitation programs in their clinics, the authors discuss the following practical solutions: a) find the most appropriate prehabilitation program for each patient; b) raise awareness among peers; c) develop evidence to demonstrate the effectiveness of prehabilitation; d) expand the interdisciplinary team; e) expand your network and make use of existing assets; f) utilize learnings from the COVID-19 pandemic.

BackgroundRadioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinico-pathological and molecular prognostic factors in survival remains controversial, resulting in difficulty in selecting patients for new targeted therapies. We assessed mortality rate and DTC-specific survival in Middle Eastern RAIR-DTC to identify prognostic factors associated with survival.MethodsThis single center, retrospective study enrolled 268 patients with RAIR-DTC. Mortality rate and DTC-specific survival were analyzed to identify prognostic factors related to survival. Univariate and multivariate analysis were performed using Cox proportional hazards model.ResultsOf the 268 cases of RAIR-DTC, 40.3% (108/268) had absent 131I uptake (either on diagnostic or post-therapy whole body scan), 15.3% (41/268) had progressive disease (PD) despite 131I, 7.5% (20/268) had persistent disease despite cumulative activity of I131 of >600 mCi and 36.9% (n=99/268) developed distant metastasis. On multivariate analysis, age (more than 45 years), presence of metastatic disease and tumors harboring telomerase reverse transcriptase (TERT) promoter mutations were independent prognostic factors for poor DTC-specific survival. Subjects were divided into 3 groups according to the number of risk factors; low risk (no risk factors); intermediate (≤ 2 risk factors); and high risk (all the 3 risk factors). Ten-year DTC-specific survival rates in low, intermediate and high-risk groups were 100.0%, 92.9% and 53.6%, respectively.ConclusionsThe contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and TERT mutations could be used as early predictors of RAIR-DTC cases. The identification of prognostic factors for poor survival in RAIR-DTC may improve the selection of patients for more personalized surveillance and therapeutic modalities.

Objectives: This study aims to assess the impact of care consumption patterns and individual characteristics on the cost of treating differentiated thyroid carcinoma (DTC), in France, with a specific emphasis on socioeconomic position.Methods: The methodology involved a net cost approach utilising cases from the EVATHYR cohort and controls from the French National Health Insurance database. Care consumption patterns were created using Optimal Matching and clustering techniques. The individual characteristics influence on patterns was assessed using multinomial logistic regression. The individual characteristics and patterns influence on care costs was assessed using generalised estimating equations.Results: The findings revealed an average cost of €13,753 per patient during the initial 3 years. Regression models suggested the main predictors of high DTC specific care consumption tended to include having a high risk of cancer recurrence (OR = 4.97), being a woman (OR = 2.00), and experiencing socio-economic deprivation (OR = 1.26), though not reaching statistical significance. Finally, high DTC-specific care consumers also incurred higher general care costs (RR = 1.35).Conclusion: The study underscores the increased costs of managing DTC, shaped by consumption habits and socioeconomic position, emphasising the need for more nuanced DTC management strategies.

Background: Active surveillance has been proposed as an appropriate management strategy for low-risk differentiated thyroid cancer (DTC), due to the typically favorable prognosis of this condition. This systematic review examines the benefits and harms of active surveillance vs. immediate surgery for DTC, to inform the updated American Thyroid Association guidelines. Methods: A search on Ovid MEDLINE, Embase, and Cochrane Central was conducted in July 2021 for studies on active surveillance vs. immediate surgery. Studies of surgery vs. no surgery for DTC were assessed separately to evaluate relevance to active surveillance. Quality assessment was performed, and evidence was synthesized narratively. Results: Seven studies (five cohort studies [N = 5432] and two cross-sectional studies [N = 538]) of active surveillance vs. immediate surgery, and seven uncontrolled treatment series of active surveillance (N = 1219) were included. One cross-sectional study was rated fair quality, and the remainder were rated poor quality. In patients with low risk (primarily papillary), small (primarily ≤1 cm) DTC, active surveillance, and immediate surgery were associated with similar, low risk of all-cause or cancer-specific mortality, distant metastasis, and recurrence after surgery. Uncontrolled treatment series reported no cases of mortality in low-risk DTC managed with active surveillance. Among patients managed with active surveillance, rates of tumor growth were low; rates of subsequent surgery varied and primarily occurred due to patient preference rather than tumor progression. Four cohort studies (N = 88,654) found that surgery associated with improved all-cause or thyroid cancer mortality compared with nonsurgical management, but findings were potentially influenced by patient age and tumor risk category and highly susceptible to confounding by indication; eligibility for, and receipt of, active surveillance; and timing of surgery was unclear. Conclusions: In patients with small low-risk (primarily papillary) DTC, active surveillance and immediate surgery may be associated with similar mortality, risk of recurrence, and other outcomes, but methodological limitations preclude strong conclusions. Studies of no surgery vs. surgery are difficult to interpret due to clinical heterogeneity and potential confounding factors and are unsuitable for assessing the utility of active surveillance. Research is needed to clarify the benefits and harms of active surveillance and determine outcomes in nonpapillary DTC, larger (>1 cm) cancers, and older patients.

Objective: The inflammatory microenvironment has been implicated in differentiated thyroid cancer (DTC). Inflammatory stimuli induce the release of components of neutrophils into extracellular space, leading to formation of neutrophil extracellular trap (NET), which can stimulate growth and progression of cancer. Generation of activated factor XII and thrombin is also involved in cancer progression. This study attempted to determine whether the level of circulating markers of NET, activated factor XII, and endogenous thrombin potential may be useful for detecting the recurrence of DTC. Methods: A total of 122 patients with DTC were recruited during the postoperative follow-up period. Measurement of the levels of circulating markers of NET (neutrophil elastase, histone–DNA complex, cell-free dsDNA), activated factor XII, and endogenous thrombin potential was performed. Results: A significantly elevated level of neutrophil elastase was detected in patients with recurrence (n = 12) compared to those without recurrence (n = 110), while significant elevation of the levels of other markers was not observed. The value for area under the curve (0.717, P = 0.018) of neutrophil elastase for detecting recurrence of DTC was superior to that (0.661, P = 0.051) of serum thyroglobulin. An elevated level of neutrophil elastase was significantly associated with recurrence of DTC independent of serum thyroglobulin. Conclusions: Because an elevated level of neutrophil elastase was detected in patients with recurrence of DTC and showed a significant association with recurrence of DTC, it can be proposed as a novel biomarker for use in detecting recurrence of DTC along with other tests.

Background: Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. Objective: The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). Patients and methods: One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. Results: After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/ InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Conclusions: Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

The aim of the study was to report on the experience in a single tertiary cancer center about the treatment and outcome of patients with Graves’ disease (GD) and metastatic thyroid cancer as compared with patients without GD in our country.

INTRODUCTION: Differentiated thyroid cancer (DTC) in adolescents rare but with a favorable outcome, despite higher rates of cervical lymph node and pulmonary metastasis compared to adults. The aim of this study was to critically evaluate treatment of adolescents with DTC at a single center. METHODS: Patients receiving postoperative radioiodine treatment (RAIT) for DTC between 2005 and 2020 at our institution were screened to identify adolescents according to the World Health Organization definition (10-19 years of age). Demographics, clinico-pathological characteristics, treatment and outcome were analyzed. RESULTS: Among 1,897 DTC patients, 23 (1.3%) were adolescents with a median (range) age of 16 (10-18) years. The female to male ratio was 3.6: 1. Sixty percent had classic papillary thyroid cancer, with follicular variant in 40%, which was higher than previously reported (15-25%) for this age group. pT-status was pT1 in 9 (39.2%), pT2 in 8 (34.8%), pT3 in 3 (13%) and pT4 in 3 (13%) patients. In 19 (82.6%) patients, central lymphadenectomy was performed and metastasis was seen in 57%. All patients received RAIT with initial activities of 1.2 (n=1, 4.3%), 2 (n=12, 52.2%) or 3.7 GBq (n=10, 43.5%). Eighteen (78.2%) patients were free of biochemical and radiologic disease at a median follow-up of 60.7 months. Second-line surgery for lymph node relapse was necessary in 3 (13%) cases. There was one disease-associated death. DISCUSSION AND CONCLUSION: Despite high rates of metastasis, most patients were cured, and second-line surgery was rarely required. Further prospective studies are needed to determine whether less aggressive surgical management or omitting adjuvant RAIT are feasible in patients with limited stages at diagnosis.

Background: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. Methods: With the aim of providing suggestions that can be useful in ev eryday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiat ed thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. Conclusions: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. Whil e the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

Timeliness of accurate dynamic observation and a clear understanding of the treatment response guarantees health of patients with differentiated thyroid cancer. Multidimensional approach to evaluation of thyroid-stimulating hormone, tumor markers, ultrasound picture, as well as results of molecular imaging with radioactive iodine is clearly defined in international clinical guidelines. At the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center for more than 15 years tactics of control exam 6 months after radioactive iodine ablation has been implemented. The aim of the current article is to consider the sequence of diagnostic search for different responses to treatment of differentiated thyroid cancer.

Purpose: To determine whether thyroid-stimulating hormone level ≥ 30 mU/L is necessary for radioiodine (131I) remnant ablation (RRA) in patients with differentiated thyroid cancer (DTC), as well as its influencing factors and pre dictors. Methods: A total of 487 DTC patients were retrospectively enrolled in t his study. They were divided into two groups (TSH < 30 and ≥ 30 mU/L) and further divided into eight subgroups (0–

Objective(s): The traditional practice of empiric radioiodine (I-131) prescription is scientifically obsolete and inappropriate for inoperable metastatic differentiated thyroid cancer. However, theranostically guided prescription is still years away for many institutions. A personalized predictive method of radioiodine prescription that bridges the gap between empiric and theranostic methods is presented. It is an adaptation of the “maximum tolerated activity” method, where serial blood sampling is replaced by population kinetics carefully chosen by the user. It aims to maximize crossfire benefits within safety constraints to overcome tumour absorbed dose heterogeneity for a safe and effective first radioiodine fraction i.e., the First Strike.Methods: The EANM method of blood dosimetry was incorporated with population kinetics, marrow and lung safety constraints, body habitus and clinical assessment of metastatic extent. Population data of whole body and blood kinetics in patients with and without metastases, prepared by recombinant human thyroid stimulating hormone or thyroid hormone withdrawal, and the maximum safe marrow dose rate were deduced from published data. For diffuse lung metastases, the lung safety limit was linearly scaled by height and separated into lung and remainder-of-body components.Results: The slowest whole body Time Integrated Activity Coefficient (TIAC) amongst patients with any metastases was 33.5±17.0 h and the highest percentage of whole body TIAC attributed to blood was 16.6±7.9%, prepared by thyroid hormone withdrawal. A variety of other average radioiodine kinetics is tabulated. Maximum safe marrow dose rate was deduced to be 0.265 Gy/h per fraction, where blood TIAC is normalised to administered activity. An easy-to-use calculator was developed which only requires height, weight and gender to populate recommendations for personalized First Strike prescription. The user decides by clinical gestalt whether the prescription is to be constrained by marrow or lung, then selects an activity depending on how extensive the metastases are likely to be. A Standard Female with oligometastasis and good urine output without diffuse lung metastasis is expected to safely tolerate 8.03 GBq of radioiodine as the First Strike.Conclusion: This predictive method will help institutions rationalise the First Strike prescription based on radiobiologically sound principles, personalised to individual circumstances.

IntroductionTheoretical models of health behavior are important guides for disease prevention and detection, treatment and rehabilitation, and promotion and maintenance of physical and mental health, but there are no intervention studies related to differentiated thyroid cancer (DTC) that use theoretical models of health as a guide. In this study, we used a microblogging platform as an intervention vehicle and mobile patient-doctor interactive health education as a means of intervention, with the aim of improving the health behaviors of DTC patients as well as the corresponding clinical outcomes.MethodsThis research project is a quantitative methodological study, and the trial will be a single-blind, single-center randomized controlled trial conducted at the Fourth Hospital of Harbin Medical University in Harbin, Heilongjiang Province. The study subjects are patients over 18 years of age with differentiated thyroid cancer who were given radioactive iodine-131 therapy as well as endocrine therapy after radical surgery for thyroid cancer. The intervention group will receive MTM-mhealth, and the realization of health education will rely on the smart terminal WeChat platform. Routine discharge education will be given to the control group at discharge. The primary outcome will be change in thyroid-stimulating hormone (TSH) from baseline and at 3 and 6 months of follow-up, and secondary outcomes will include change in self-management behavior, social cognitive and psychological, and metabolic control.DiscussionThis study will explore a feasible mHealth intervention program applied to a population of DTC patients using the Multi-theory model of health behavior change (MTM) as a guide, with the aim of evaluating the MTM-based intervention program for clinical outcome improvement in DTC patients, as well as determining the effectiveness of the MTM-based intervention program in improving self-management skills in DTC patients. The results of this study will indicate the feasibility as well as the effectiveness of the application of health theoretical modeling combined with mHealth applications in disease prognostic health management models, and provide policy recommendations and technological translations for the development of mobility-based health management applications in the field of health management.

BackgroundResearch has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causality of circulating lipoprotein lipids on DTC.MethodsMendelian randomization (MR) analysis was conducted to evaluate the relationship between the circulating lipoprotein lipids and DTC risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association (GWA) study containing a high-incidence Italian population of 690 cases samples with DTC and 497 controls.ResultsUnivariate and multivariate mendelian randomization analysis demonstrated that ‘total cholesterol’, ‘HDL cholesterol’, ‘apolipoprotein B’ and ‘ratio of apolipoprotein B to apolipoprotein A1’ were correlated with DTC. According to sensitivity analysis, our results were reliable. Furthermore, multivariate analysis revealed that there is no causative association between DTC and any of the many cause factors when they interact with one another, suggesting that there was a deep interaction between the four factors, which could affect each other. Finally, the mechanism of the related effects each other as well as the target genes with significant SNP regulatory effects in DTC was explored by conducting functional enrichment analysis and constructing the regulatory networks.ConclusionsWe obtained four exposure factors (total cholesterol, HDL cholesterol, apolipoprotein B and ratio of apolipoprotein B to apolipoprotein A1) closely related to DTC, which laid a theoretical foundation for the treatment of DTC.

Differentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy worldwide and requires effective prognostic markers and therapeutic targets to optimize patient outcomes. This study investigated the potential of human serum albumin (HSA) cysteine-34 (Cys34) redox state as a prognostic indicator and therapeutic avenue for DTC. A retrospective cohort study of 99 patients with DTC undergoing radioactive iodine therapy found that higher concentrations of HSA with the reduced form of Cys34 (i.e., human mercaptalbumin [HMA]) were associated with improved progression-free survival in metastatic DTC. In vitro experiments using a DTC cell line revealed that HMA induced cytotoxic effects by triggering ferroptosis, characterized by lipid peroxidation, intracellular ROS accumulation, and decreased cell viability. Ferroptosis inhibitors rescued cell viability, confirming their role in cytotoxicity. These results implicate the HSA-Cys34 redox state is a promising avenue for precision medicine in DTC, shedding light on the prognostic relevance and therapeutic potential of HMA-induced ferroptosis. They emphasize the opportunity for personalized treatment strategies to advance the management of patients with DTC. [Display omitted] • High plasma mercaptalbumin predicts improved prognosis in differentiated thyroid carcinoma. • Mercaptalbumin promotes lipid peroxidation in differentiated thyroid cancer cells. • Mercaptalbumin induces ferroptosis in differentiated thyroid cancer cells. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and the treatment effect of iodine 131 (131Ⅰ) thyroidectomy after operation for differentiated thyroid cancer (DTC) and the predictive value of the effect of 131I thyroidectomy after DTC operation. Methods: 150 DTC patients who underwent thyroidectomy and underwent 131Ⅰ thyroidectomy after operation in Xuzhou Hospital Affiliated to Jiangsu University from March 2019 to December 2021 were selected as the study subjects, and the patients were divided into successful thyroidectomy group (107 cases) and unsuccessful thyroidectomy group (43 cases) according to the effect of 131Ⅰ thyroidectomy, neutrophil count, platelet count, lymphocyte count were obtained by blood routine examination and NLR and PLR were calculated, and the NLR and PLR were compared between the two groups. The influencing factors of 131Ⅰ thyroidectomy efficacy was analyzed by single factor and multiple factor logistic regression model, and the predictive value of NLR and PLR on the efficacy of 131Ⅰ thyroidectomy was analyzed by receiver operating characteristic curve (ROC). Results: The NLR and PLR in the successful thyroidectomy group were lower than those in the unsuccessful thyroidectomy group (P＜0.05), single factor analysis showed that the levels of thyroid stimulating hormone (TSH) was higher than that in the unsuccessful thyroidectomy group, thyroglobulin (Tg) in the successful thyroidectomy group was lower than those in the unsuccessful thyroidectomy group, and the maximum diameter of the lesion in the successful thyroidectomy was smaller than that in the unsuccessful thyroidectomy group (P＜0.05) .Multivariate logistics regression analysis showed that, high NLR, PLR and Tg were independent risk factors for failure of 131Ⅰ thyroidectomy (P＜0.05) .The area under ROC curve (AUC) of NLR, PLR and combined detection predicting the efficacy of 131Ⅰ thyroidectomy was 0.760, 0.732, 0.829respectively, and the AUC of NLR and PLR combined detection was higher than that of the two alone. Conclusion: High NLR and PLR are independent risk factors for unsuccessful 131Ⅰ thyroidectomy after DTC operation, and early detection of NLR and PLR levels has good predictive value for the efficacy of 131Ⅰ thyroidectomy after DTC operation. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) includes papillary (PTC), follicular and Hürthle-cell carcinomas. They develop from thyroid follicular epithelium. Thyroid cancer (TC) is found in approximately 5% of thyroid nodules and the most common type is PTC – over 90%. The number of DTC survivors has increased worldwide due to the rising incidence of the disease. Quality of life (QoL) in DTC survivors is a very relevant topic because the disease is mainly diagnosed during the peak earning years (30-50 years of age) and has high 10-year survival rate. Few studies on this topic have been published in recent years, applying different QoL questionnaires (general and specific). The majority of researches demonstrated that DTC had negative impact on QoL despite the good disease prognosis. Moreover, some studies reported similar or worse QoL in patients with DTC compared to patients treated for other malignancies, with poorer prognosis and more aggressive treatment. It can be speculated that DTC patients have needs that are underestimated by medical professionals. More studies in the field are needed in order to develop precise postoperative care plans for DTC patients. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37–1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy. [ABSTRACT FROM AUTHOR]

Objective: The 2015 American Thyroid Association guidelines recommend against radioiodine (RAI) ablation for patients with low‐risk papillary microcarcinoma. However, its role in other low‐risk differentiated thyroid cancer (DTC) patients remains controversial. Here, we compare long‐term outcomes with RAI versus no‐RAI in a large cohort comprising all low‐risk DTCs. Methods: Patients with low‐risk, histologically‐proven DTC post‐thyroidectomy, treated with RAI or kept on follow‐up without RAI, between 1990 and 2019 were included. The main outcomes included recurrence rate and recurrence‐free survival (RFS), and were validated by propensity‐score matching analysis. Results: Of the 2074 low‐risk DTC patients (median age: 35 years), 1686 patients underwent RAI‐ablation (RAI group), while 388 patients underwent no‐RAI follow‐up (NOI group). Over a median follow‐up of 8 years (range: 3–29), the recurrence rates were similar between the RAI and NOI groups (2.0% vs. 3.3%, p =.161). The 5‐ and 10‐year RFS probabilities were 99.2% and 97.4%, respectively in RAI group versus 98.4% and 96.2%, respectively, in NOI group (p =.055). Subgroup regression analyses showed that patients with age <55 years (p =.044), male sex (p =.015), papillary histology (p =.043), pT3a tumours (p =.049) and postoperative thyroglobulin ≥5 ng/mL (p =.002) had significantly better RFS with RAI compared to NOI follow‐up. Propensity‐score matching generated 776 matched pairs with no significantly different outcomes between the two groups. Conclusions: In low‐risk DTC patients post‐thyroidectomy, RAI ablation does not confer significant survival advantage over no‐RAI follow‐up. Further studies are required to demonstrate any long‐term benefit with RAI, specifically in patients with tumour size >4 cm and elevated postoperative thyroglobulin. [ABSTRACT FROM AUTHOR]

Over the past 3 decades, advances in the molecular genetics of thyroid cancer (TC) have been translated into diagnostic tests, prognostic markers, and therapeutic agents. The main drivers in differentiated TC pathogenesis are single-point mutations and gene fusions in components of the Mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. Other important genetic alterations in the more advanced types of TC include TERT promoter, TP53, EIF1AX, and epigenetic alterations. Using this knowledge, several molecular tests have been developed for cytologically indeterminate thyroid nodules. Currently, 3 commercially available tests are in use including a DNA/RNA-based test (ThyroSeq v.3), an RNA-based test (Afirma Gene Sequencing Classifier), and a hybrid DNA/ miRNA test, ThyGeNEXT/ThyraMIR. These tests are mostly used to rule out malignancy in Bethesda III and IV thyroid nodules because they all have high sensitivities and negative predictive values. Their common use, predominantly in the United States, has resulted in a significant reduction in unnecessary thyroid surgeries for benign nodules. Some of these tests also provide information on the underlying molecular drivers of TC; this may support decision making in initial TC management planning, although this practice has not yet been widely adopted. More importantly, molecular testing is essential in patients with advanced disease before using specific mono-kinase inhibitors (eg, selpercatinib for RET-altered TC) because these drugs are ineffective in the absence of a specific molecular target. This mini-review discusses the utilization of molecular data in the clinical management of patients with thyroid nodules and TC in these different clinical situations. [ABSTRACT FROM AUTHOR]

Background: Despite their excellent prognosis, children and young adults (CAYA) with differentiated thyroid cancer (DTC) tend to have more frequent occurrence of distant metastasis (DM) compared to adult DTC. Data about DM in CAYA from Middle Eastern ethnicity is limited. Methods: Medical records of 170 patients with DTC ≤18 years were retrospectively reviewed. Clinico-pathological factors associated with lung metastasis in CAYA, their clinical presentation and outcome were analyzed. Rick factors related to distant metastasis-free survival (DMFS) for the whole cohort were evaluated. Results: DM was observed in 27 patients and all were lung metastasis. Lung metastasis was significantly associated with younger age (=15 years), extrathyroidal extension (ETE), multifocal tumors, bilaterality, presence of lymph node (LN) disease and high post-operative stimulated thyroglobulin (sTg). Highest negative predictive values were seen with low post-operative sTg (97.9%), absence of LN disease (93.8%), absence of ETE (92.2%) and age older than 15 years (92.9%). Post-therapy whole body scan (WBS) identified most of the lung metastasis (21 of 27; 77.8%). Upon evaluating patients response according to ATA guidelines, excellent response was seen in only one patient, while biochemical persistence and structural persistence were seen in 11.1% (3/27) and 77.8% (21/27), respectively. Elevated post-operative sTg (>10ng/ml) was the only risk factor found to be significantly associated with both biochemical persistence (with or without structural persistence (p = 0.0143)) and structural persistence (p = 0.0433). Cox regression analysis identified age and postoperative sTg as independent risk factors related to DMFS. Based on these two risk factors for DMFS, patients were divided into 3 groups: low risk (no risk factors), intermediate risk (1 risk factor) and high risk (both risk factors). 20-year DMFS rates in the low-, intermediate- and high-risk groups were 100.0%, 81.3% and 23.7% respectively (p < 0.0001). Conclusion: Higher suspicion for metastatic pediatric DTC should be considered in patients who are young, have LN disease, extrathyroidal extension and elevated post-operative sTg. Persistent disease, despite therapy, is very common and it appears to be related to post-operative sTg level. Hence, risk adaptive management is desirable in CAYA with DTC. [ABSTRACT FROM AUTHOR]

Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathologicalstaging systems. Patients and methods: We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis. Results: Of 296 patients tested, 137 (46.3%) had BRAFV600E-positive tumors and 72 (24.3%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) (P 0.12). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (P <0.0001). TERT promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. Conclusion: TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on TgAb-positive differentiated thyroid cancer (DTC) patients. Methods: In this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT. Results: The ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg x pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all p-values <0.05). The receiver operating characteristic (ROC) curves showed that the cutoff value was 724.25 IU/ml, 424.00 IU/ml, and 59.73 for preop-TgAb, pa-TgAb, and sTg x pa-TgAb, respectively. The multivariate logistic regression analysis results indicated that pa-TgAb, sTg x pa-TgAb, initial RAIT dose, and N stage were independent risk factors for NER (all p-values <0.05). For the Kaplan- Meier analysis of disease-free survival (DFS), the median DFS of the patients with sTg x pa-TgAb < 59.73 and initial RAIT dose < 100 mCi was significantly longer than that of the patients with sTg x pa-TgAb > 59.73 (50.27 months vs. 48.59 months, p = 0.041) and initial RAIT dose >100 mCi (50.50 months vs. 38.00 months, p = 0.030). Conclusion: We found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients. [ABSTRACT FROM AUTHOR]

Objective: Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and metaanalysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0–19 years. Methods: The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC. Results: After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33–0.59) and 0.07 (95% CI: 0.02–0.12) per 100,000 personyears, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities. Conclusion: Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk factors of second primary malignant tumor (SPMT) in patients with differentiated thyroid cancer (DTC) and establish a competing risk nomogram to predict the probability of SPMT occurrence. Methods: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with DTC between 2000 and 2019. The Fine and Gray subdistribution hazard model was employed to identify SPMT risk factors in the training set and develop a competing risk nomogram. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: A total of 112,257 eligible patients were included in the study and randomized into a training set (n = 112,256) and a validation set (n = 33,678). The cumulative incidence rate of SPMT was 15% (n = 9528). Age, sex, race, tumor multifocality, and TNM stage were independent risk factors of SPMT. The calibration plots showed good agreement between the predicted and observed SPMT risks. The 10-year AUCs of the calibration plots were 70.2 (68.7–71.6) in the training set and 70.2 (68.7–71.5) in the validation set. Moreover, DCA showed that our proposed model resulted in higher net benefits within a defined range of risk thresholds. The cumulative incidence rate of SPMT differed among risk groups, classified according to nomogram risk scores. Conclusion: The competing risk nomogram developed in this study exhibits high performance in predicting the occurrence of SPMT in patients with DTC. These findings may help clinicians identify patients at distinct levels of risk of SPMT and develop corresponding clinical management strategies. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility of individualized management of postoperative patients with differentiated thyroid cancer by a mode based on internet and programming technology. Methods: The enrolled patients were randomly divided into the study group and the control group. The study group used a mobile application to collect patient information, evaluate the risk of thyroid cancer recurrence and levothyroxine medication risk, develop individual thyrotropin control targets, and push levothyroxine adjustment recommendations to patients. In the control group, the traditional outpatient follow-up mode was used. Results: Two hundred patients were randomly divided into the study group and the control group at a 1:1 ratio. There was no significant difference in the physical and chemical indices between the two groups at baseline. During the 1-year follow-up, there was no significant difference in the thyrotropin attainment rate, heart rate or bone mineral density between the study group and the control group. During the 2-year follow-up, the thyrotropin attainment rate of the study group was better than that of the control group. The total score of Symptom Checklist 90 of the study group was lower than the control group, and satisfaction with the treatment was significantly higher than that of the control group. Conclusion: The management based on the internet and programming technology is not inferior to the traditional outpatient follow-up mode, and is beneficial to improve patients' quality of life, promote the implementation of the national graded diagnosis and treatment system and the grassroots management of chronic diseases. [ABSTRACT FROM AUTHOR]