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Purpose The treatment of recurrent thyroid cancer with critical organ invasion is challenging. The combination of radiofrequency ablation (RFA) and external beam radiation therapy (EBRT) has been proposed as an effective option. This study evaluates outcomes for inoperable residual/recurrent differentiated thyroid cancer (rDTC) patients treated with RFA followed by EBRT.Materials and Methods Patients with rDTC treated with RFA followed by EBRT were retrospectively studied. RFA was performed using a free‐hand, ‘moving‐shot’ technique under US or CT guidance. For lesions invading critical structures intolerant to ‘en bloc’ high-temperature RFA, limited-field EBRT using 6‐ or 10‐MV photons was used for adjuvant treatment at a dose of 66 Gy in 33 daily fractions. Toxicities and outcomes were reviewed.Results Between April 2020 and January 2022, 11 patients with 14 rDTC lesions underwent RFA followed by EBRT. Five patients had metastatic lesions at rDTC diagnosis. With a median follow-up period of 33.7 months, all patients maintained locoregional control, while achieving a 2-year survival rate of 90.9%. This combined treatment achieved a volume reduction ratio of 92.1% ± 5.1%. The mean nadir thyroglobulin level in patients without initial distant metastases after treatment was 1.40 ± 0.81 ng/ml. Regarding treatment-related complications, one patient (9%) experienced temporary hoarseness after RFA, grade 2 radiation dermatitis occurred in 3 patients (27.2%), and grade 2 dysphagia was noted in 4 patients (36.4%). No grade 3 or greater toxicities occurred.Conclusions Salvage RFA followed by EBRT is feasible, effective and safe for patients with rDTC.

IntroductionForkhead box E1 (FOXE1) is a transcription factor with a crucial role in thyroid morphogenesis and differentiation. Promoter hypermethylation downregulates FOXE1 expression in different tumor types; nevertheless, its expression and relationship with methylation status in differentiated thyroid cancer (DTC) remain unclear.MethodsA total of 33 pairs of matched samples of PTC tumors and non-tumors were included. Tumor cell cultures were treated with either 5-Aza-2′-deoxycytidine demethylating agent or dimethyl sulfoxide (DMSO). A real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to assess FOXE1 expression. The methylation status was quantified using bisulfite sequencing. A luciferase gene assay was used to determine CpG-island functionality. Gene expression and promoter methylation of FOXE1 and FOXE1-regulated genes were also analyzed with data from The Cancer Genome Atlas (TCGA) thyroid samples.ResultsAfter demethylating treatment, increased FOXE1 mRNA was observed concomitantly with reduced promoter methylation of CpGisland2. A negative correlation between mRNA downregulation and an increased methylation level of CpGisland2 was observed in tumors. Diminished protein expression was also detected in some DTC cell lines and in some tumor samples, suggesting the involvement of post-transcriptional regulatory mechanisms. CPGisland2 was proved to be an enhancer. TCGA data analysis showed low FOXE1 mRNA expression in tumors with a negative correlation with methylation status and a positive correlation with the expression of most of its target genes. Reduced FOXE1 expression, accompanied by a high methylation level, was associated with PTC aggressiveness (tall cell variant, advanced extra thyroid extension, T4 American Joint Committee on Cancer (AJCC) classification), age at diagnosis (over 45 years old), and presence of a BRAFV600E mutation.ConclusionFOXE1 mRNA was downregulated in DTC compared with non-tumors, followed by high CpGisland methylation. A coupling of low mRNA expression and high methylation status was related to characteristics of aggressiveness in DTC tumors.

IntroductionPlasma cell-free DNA (cfDNA) estimation offers a non-invasive method to potentially diagnose, monitor, and prognosticate patients with malignancy. This prospective study aimed to assess plasma cfDNA levels in patients with differentiated thyroid cancer (DTC) to determine its role in predicting disease status in the post-operative setting.Materials and methodsThis was a single-center prospective observational study conducted at a public medical research university and hospital in New Delhi, India. 254 patients with DTC in the post-operative setting were included: 95 in Group 1 (active structural disease) and 159 in Group 2 (disease-free). Blood samples were collected for plasma separation and cfDNA extraction. The cfDNA concentrations were quantified and compared across various disease states.ResultsMedian values of plasma cfDNA (ng/µL) in groups 1 and 2 were found to be 0.272 (IQR: 0.137-0.442) and 0.222 (IQR: 0.123-0.398), respectively with no significant difference (p=0.122). cfDNA levels were significantly higher in patients in the age group ≥55 years (p=0.016). However, the cfDNA levels were not significantly associated with any of the other known prognostic markers of DTC.DiscussionBased on the results of this study, plasma cfDNA levels did not significantly predict disease status in patients with DTC in the post-operative setting.

BackgroundLimited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC).MethodsIn this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more.ResultsIn our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest.ConclusionsIn long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II.

BackgroundDifferentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy with a recurrence rate of about 20%, necessitating better predictive methods for patient management. This study aims to create a relational classification model to predict DTC recurrence by integrating clinical, pathological, and follow-up data.MethodsThe balanced dataset comprises 550 DTC samples collected over 15 years, featuring 13 clinicopathological variables. To address the class imbalance in recurrence status, the Synthetic Minority Over-sampling Technique for Nominal and Continuous (SMOTE-NC) was utilized. A hybrid model combining classification algorithms with association rule mining was developed. Two relational classification approaches, regularized class association rules (RCAR) and classification based on association rules (CBAR), were implemented. Binomial logistic regression analyzed independent predictors of recurrence. Model performance was assessed through accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score.ResultsThe RCAR model demonstrated superior performance over the CBAR model, achieving accuracy, sensitivity, and F1 score of 96.7%, 93.1%, and 96.7%, respectively. Association rules highlighted that papillary pathology with an incomplete response strongly predicted recurrence. The combination of incomplete response and lymphadenopathy was also a significant predictor. Conversely, the absence of adenopathy and complete response to treatment were linked to freedom from recurrence. Incomplete structural response was identified as a critical predictor of recurrence risk, even with other low-recurrence conditions.ConclusionThis study introduces a robust and interpretable predictive model that enhances personalized medicine in thyroid cancer care. The model effectively identifies high-risk individuals, allowing for tailored follow-up strategies that could improve patient outcomes and optimize resource allocation in DTC management.

Objective: To explore the changes of serum ps-Tg, MMP-13, and TgAb in patients with differentiated thyroid carcinoma before and after surgery, and their correlation with postoperative recurrence and metastasis. Methods: 100 differentiated thyroid cancer patients admitted from 2018.1 to 2021.1 in our hospital were treated with radical surgery for 3-year follow-up to record the changes in serum level. The incidence of postoperative recurrence and metastasis was recorded and divided into recurrence group (n = 25) and non-recurrence group (n = 75) Comparing serum levels, Spearman correlation analysis and predicted value was used for logistic regression analysis. Result: The levels of ps-Tg, MMP-13 and TgAb were lower than before surgery (P < 0.05) However, there was no difference in 1 year compared with 3 years after surgery (P > 0.05) ; The expression level and percentage decrease of serum ps-Tg, MMP-13 and Tg Ab between 1-year patients of recurrence and non-recurrence patients, The group with recurrent metastasis was higher than the non-recurrent metastasis group (P < 0.05) ; Spearman Correlation analysis showed that ps-Tg, MMP-13 and TgAb were positively correlated with the recurrence and metastasis of differentiated thyroid carcinoma after surgery (P < 0.05) ; logistics From the regression model analysis, The ps-Tg, MMP-13 and TgAb were all classified as independent influencing factors (P < 0.05) Conclusion: The serum levels of ps-Tg, MMP-13, and TgAb gradually decrease in patients with differentiated thyroid cancer after surgery for 1 year, and show a stable state from 1 to 3 years after surgery. The serum levels of ps-Tg, MMP-13, and TgAb are closely related to the postoperative recurrence and metastasis. [ABSTRACT FROM AUTHOR]

The radioiodine therapy is a one of the basic elements at combined treatment of differentiated thyroid cancer and is an alternative method for patients with distant metastases and a potentially high risk of tumor recurrence. It has been used in clinical practice for more than 80 years. The first report on the phenomenon of accumulation of 130I/131I in a metastatic focus of differentiated thyroid cancer was published by A. Keston et al. in 1942, and in 1946, the production of 131I was established, and the drug became available. In our country, radioiodine therapy has been widely used for the treatment of differentiated thyroid cancer since 1982.This article presents methodological recommendations for radioiodine therapy of patients with differentiated thyroid cancer, provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches treatment of this disease.

Introduction. The multikinase inhibitors have demonstrated high clinical efficacy in treatment of the radioiodine refractory differentiated thyroid cancer. At the same time, the inclusion criteria in the studies has reflected a minimum set of characteristics important for beginning of use of these drugs and an approach that takes into account the tumor progression rate (the volume doubling time) in the absence of clinical manifestations of the disease that have made it possible to individualize the start of therapy. Aim. To describe and evaluate the barriers and drivers of use the “watch and wait” approach by Russian oncologists in treatment of the radioiodine refractory thyroid cancer. Materials and methods. We conducted 35 structured interviews with oncologists observing patients after radioiodine therapy in order to evaluate the “watch and wait” approach. unfortunately, data on use and prevalence of this approach in Russia are limited. The present study involved the use of deductive content analysis as well as analysis of implementation model of clinical guidelines and included investigation of issue of implementation of the “watch and wait” approach to current practice of therapy for radioiodine refractory differentiated thyroid cancer. One of the main tasks was to determine the influence of external factors on the treatment of this category of patients. Conclusion. Barriers and drivers of using “watch and wait” approach in the treatment of differentiated radioiodine refractory thyroid cancer are identified at several levels. for wide use of this approach, it is necessary to involve oncologists taking into account their attitude regarding changes in routine practices, patient expectations and to obtain additional data regarding its long-term effectiveness.

Objectives: The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI). Methods: Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict noniodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter. Results: The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from =10mm to =4mm, the AUCs remained relatively stable, for smallest nodules (=4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment. Conclusion: This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Methods: Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. Results: The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. Conclusions: This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed. [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow‐up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri‐menopausal women, 111 in post‐menopausal women, and 70 in men) and 706 cancer‐free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre‐menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, ptrend =.06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, ptrend =.06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, ptrend =.07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post‐menopausal women and men but may suggest an involvement of altered sex steroid production in pre‐menopausal women. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis (LNM) has an important role for the prognosis of differentiated thyroid cancer (DTC). The aim of the study was to investigate the effect of clinicopathologic parameters on cervical LNM in DTC. Methods: The patients who underwent thyroidectomy along with neck dissection were analyzed retrospectively. Results: Of the 150 patients diagnosed with DTC who underwent neck dissection, 1 had follicular thyroid carcinoma and 149 had papillary thyroid carcinoma (PTC). The median tumor size was 14.0 mm. The tumor diameter with the highest specificity and sensitivity for the detection of LNM was ≥11.5 mm. Extrathyroidal extension (ETE) was observed in 35.3% of the patients. The rate of multifocality in tumors with extrathyroidal spread was significantly higher than in tumors without ETE. LNM was observed in 60.0% of the patients. ETE was present in 28.9% of the tumors that had LNM. Lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margin were observed in 13.3%, 2.7%, and 14% of the patients respectively. A significant positive correlation was found between LNM and tumor diameter, ETE, positive tumor margin and LVI (Pp = .006, P = .031, P = .002, and P = .014, respectively). Conclusion: In this study, ETE, LVI, positive tumor margin, and tumor diameter greater than 11.5 mm were significantly correlated with the presence of LNM. These findings may be useful in bringing to mind the possibility of lymph node metastases that have not been able to be detected before surgery and in monitoring these patients more closely. [ABSTRACT FROM AUTHOR]

Objective The objective of this prospective study was to assess longitudinal variations in health-related quality of life (HR-QOL) in patients diagnosed with differentiated thyroid cancer (DTC) before and after thyroidectomy. Methods A cohort of 185 DTC patients who underwent thyroidectomy between January 2013 and December 2017 and who completed all necessary questionnaires was evaluated. Their HR-QOL was gauged using the University of Washington Quality of Life questionnaire (UW-QOL) and the City of Hope Quality of Life-Thyroid Version questionnaire (QOL-TV) both prior to surgery and at 3 months, 6 months, 1 year, 2 years, 3 years, and 5 years postoperatively. Results Out of 185 patients, 150 (81.1%) were female, with an average age of 48.7 ± 12.9 years. For both UW-QOL and QOL-TV, the total composite QOL scores notably declined from preoperative levels to 3 months postoperatively, then gradually improved over 5 years, ultimately exceeding preoperative scores. Factors such as total thyroidectomy, radioactive iodine (RAI) ablation, and postoperative hypoparathyroidism were associated with lower physical composite QOL scores. Patients who underwent remote-access thyroidectomy expressed significantly higher satisfaction with appearance compared with those who had conventional thyroidectomy. Mood and anxiety were major clinical concerns both before and after surgery, showing considerable improvement postoperatively. Conclusion For DTC patients, HR-QOL experienced a significant drop 3 months postsurgery, subsequently showing gradual improvement, surpassing preoperative QOL by 5 years. Factors contributing to improved physical QOL included the utilization of remote-access thyroidectomy, less extensive thyroidectomy, and the absence of RAI ablation and hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Background: Radioactive iodine refractory differentiated thyroid cancer (RAIRDTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinicopathological 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. Methods: This single center, retrospective study enrolled 268 patients with RAIRDTC. 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. Results: Of 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 Conclusions: The 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. [ABSTRACT FROM AUTHOR]

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb =47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored. Methods: Genome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings. Results: Four bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333-51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333-51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033-10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096-7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148-0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125-0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020-0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037-0.769, p = 0.021). Conclusion: These findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC. [ABSTRACT FROM AUTHOR]

Thyroglobulin (Tg) is an iodinated glycoprotein, which is normally stored in the follicular colloid of the thyroid, being a substrate for thyroid hormone production. Since it is produced by well-differentiated thyroid cells, it is considered a reliable tumor marker for patients with differentiated thyroid carcinoma (DTC) during their follow-up after total thyroidectomy and radioiodine ablation. It is used to monitor residual disease and to detect recurrent disease. After total thyroid ablation, unstimulated highly sensitive Tg measurements are sufficiently accurate to avoid exogenous or endogenous thyrotropin (TSH) stimulation and provide accurate diagnostic and prognostic information in the great majority of DTC patients. Adopting sophisticated statistical analysis, i.e., decision tree models, the use of Tg before radioiodine theranostic administration was demonstrated to be useful in refining conventional, pathology-based risk stratification and providing personalized adjuvant or therapeutic radioiodine administrations. The follow-up of DTC patients aims to promptly identify patients with residual or recurrent disease following primary treatment. Our review paper covers the diagnostic, theranostic and prognostic value of thyroglobulin in DTC patients. [ABSTRACT FROM AUTHOR]

Background: Although lenvatinib is the preferred treatment for unresectable radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), this agent exerts considerable toxicities, which can lead to frequent dose interruptions and modifications. The adoption of planned drug holidays has been recently suggested as one means of minimizing or avoiding these severe adverse events. Our retrospective study demonstrated that planned drug holidays appear to be a promising strategy for continuing of lenvatinib. However, the benefits of planned drug holidays in a prospective study have yet to be clarified. Here, we investigated the impact of planned drug holidays on clinical outcomes in patients treated with lenvatinib in the COLLECT study. Methods: In COLLECT, a prospective observational study, patients with RR-DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities was permitted. Furthermore, planned drug holidays were allowed to avoid severe or intolerable toxicities. The present post hoc analysis focused on evaluating the impact of planned drug holidays on clinical outcomes, including overall survival (OS), time to treatment failure (TTF), time to failure strategy (TFS), and progression-free survival (PFS), in patients in the COLLECT study who were treated with lenvatinib. Results: In total, 262 patients were included. Of the 253 patients evaluable for efficacy, 73 undertook a planned drug holiday at the discretion of the attending physician. OS, TTF, TFS, and PFS were significantly longer in patients who used a planned drug holiday than in those who did not. The planned drug holiday group demonstrated notable clinical outcomes, with a 1-year OS of 95.8% and a 1-year PFS of 94.5%. Moreover, planned drug holidays demonstrated a clinically meaningful advantage in clinical outcomes. The planned drug holiday group had a significantly longer duration of administration at a dose of ≥10 mg. Conclusions: Planned drug holidays for lenvatinib were associated with significantly improved clinical outcomes compared to daily oral administration. Further investigation of the optimal treatment schedule for lenvatinib is warranted. Clinical Trial Registration: UMIN000022243. [ABSTRACT FROM AUTHOR]

Introduction: The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC. Methods: Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method. Results: The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 (p = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination. Conclusions: The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs. [ABSTRACT FROM AUTHOR]

Purpose: Many countries have implemented unprecedented health measures since the World Health Organisation declared the novel coronavirus disease 2019 (COVID-19) a global pandemic. These measures have resulted in delays in the diagnosis of differentiated thyroid cancer (DTC). However, there is limited data on the impact of restrictions imposed during the pandemic on DTC management. Thus, the aim of this study is to analyse the clinicopathological and follow-up data of DTC patients diagnosed before and during the COVID-19 outbreak. Methods: This retrospective study included 191 DTC patients that were diagnosed between December 2018 and June 2021. The patients were divided into two groups: patients diagnosed before (December 2018 to February 2020) and during (March 2020 to June 2021) the COVID-19 pandemic. The clinicopathological and follow-up data between the two groups were compared. Results: Similar preoperative cytology results were obtained from the two groups. No difference with regard to tumour size, lymphovascular invasion and extrathyroidal invasion was observed between the two groups. While the American Thyroid Association risk stratification was similar between the two groups, radioactive iodine (RAI) therapy was applied less during the COVID-19 period. Although RAI therapy was administered at a lower rate during the COVID-19 period, the recurrence rates among patients after two years of follow-up were similar to those during the pre-COVID-19 period. Conclusion: Although the COVID-19 pandemic restrictions during the pandemic period caused difficulties in the management of DTC patients, this did not negatively affect their prognosis. These findings can confirm the applicability of active surveillance in DTC patients and may help change the real-life treatment practices in selected low-risk DTC patients. [ABSTRACT FROM AUTHOR]

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy. Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases. Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders. Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Lenvatinib was approved for the treatment of patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) in the United States (US) in 2015. The main objective of the current study was to assess real-world clinical effectiveness in RAI-R DTC patients treated with first line lenvatinib monotherapy in the US. Methods: A retrospective chart review was conducted in RAI-R DTC patients who initiated lenvatinib monotherapy as first line treatment between February 2015 and September 2020. Anonymized data were abstracted by prescribing physicians from individual patient's electronic health records. Clinical outcomes included provider-reported real-world best overall response (rwBOR), real-world progression-free survival (rwPFS), and overall survival (OS). Time-to-event endpoints were assessed using Kaplan–Meier methods. Results: Our study included 308 RAI-R DTC patients treated with first line lenvatinib. At lenvatinib initiation, patients' median age was 60 years, 51.6% were female, and 26.0% of patients had an ECOG performance score of ≥2. Over the follow-up period, 32.5% of patients discontinued first line lenvatinib permanently, with others remaining on treatment. The median duration of lenvatinib therapy was 17.5 months overall. Provider-reported rwBOR (complete or partial response) to lenvatinib was 72.4%. Median rwPFS was 49.0 months. Estimated rwPFS rates at 24 and 48 months were 68.5% and 55.0%, respectively. Estimated OS rates at 24 and 72 months were 78.4% and 57.0%, respectively; median OS was not reached. Conclusion: The current study reinforces the clinical effectiveness of first line lenvatinib as standard of care in patients with RAI-R DTC in real-world clinical practice in the US. [ABSTRACT FROM AUTHOR]

Context Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC. Objective This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns. Methods A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups— BRAFV600E mutated, RAS mutated, fusions, and others—were classified according to main driver genes status. Results BRAF , TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT , TP53 , or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P =.001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E -mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS -mutated (4.5%, P <.001) and fusion-positive (20.7%, P <.001) tumors. In I-RAIA subgroups, BRAFV600E -mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions. Conclusion Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone. [ABSTRACT FROM AUTHOR]

Simple Summary: Risk stratification for differentiated thyroid cancer is a well-established tool for prognostication and selection of the appropriate initial therapy for "differentiated thyroid cancers". The current risk stratification systems include a system used in current guidelines, based on surgical pathology features identified postoperatively and a more dynamic model that includes all perioperative clinical, radiologic, and pathologic data as well as the response to initial therapy information. Theranostic risk stratification is essentially based on genomic and molecular features of the patient's individual tumor, investigated perioperatively and associated or correlated with radioactive iodine theranostics. This approach allows a more rational selection of the extent of the initial surgical treatment and subsequent radioactive iodine treatment. Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach. [ABSTRACT FROM AUTHOR]

Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4–19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2–75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4–5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018 [ABSTRACT FROM AUTHOR]

Background: The poor overall prognosis of radioiodine refractory thyroid cancer is an inevitable challenge in managing this disease. A series of trials have demonstrated the antitumor activity of tyrosine kinase inhibitors (TKIs) in radioiodine refractory differentiated thyroid cancer (RAIR‐DTC). However, the available evidence cannot determine the optimal choice of TKI in RAIR‐DTC. Methods: This study searched PubMed, EMBASE, Cochrane databases, and the ClinicalTrials website. The Cochrane bias risk tool was used to assess the risk of bias, and to evaluate randomized clinical trials (RCT) of RAIR‐DTC patients treated with the TKI system. Outcomes, including progression‐free survival (PFS), overall survival (OS), and adverse events (AEs) were reported. Results: Seven studies involving 1310 patients with RAIR‐DTC was conducted to compare the PFS and OS of various TKI monotherapies with placebo. The results showed that all TKI monotherapies had a statistically significant benefit in terms of PFS compared with placebo, with lenvatinib demonstrating the greatest benefit (hazard ratio [HR] 0.19, 95% credible interval [CrI] 0.14–0.25). In terms of OS, only apatinib (HR 0.42, 95% CrI 0.18–0.97) and anlotinib (HR 0.36, 95% CrI 0.18–0.73) showed statistically significant benefits compared with placebo. TKIs also had a higher incidence of AEs of grade 3 or higher compared with placebo. The findings suggest that lenvatinib may be the preferred TKI for the treatment of RAIR‐DTC, although its high incidence of AEs should be considered. The results also indicate that TKI treatment may be similarly effective in RAIR‐DTC patients with BRAF or RAS mutations and in those with papillary or follicular subtypes of the disease, regardless of prior TKI treatment. Conclusions: The results of this meta‐analysis suggest that targeted therapy with TKIs may be beneficial for patients with radioiodine‐refractory advanced or metastatic differentiated thyroid cancer. Among the TKIs analyzed, lenvatinib appeared to be the most effective at improving PFS, although it also had the highest incidence of AEs. Further research through direct randomized controlled trials is needed to determine the optimal choice of TKI for treating patients with RAIR‐DTC. This study is beneficial for formulating patients' treatment plans and guides clinicians' decision‐making. [ABSTRACT FROM AUTHOR]

Background: Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. Methodology: Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. Results: Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2–3 cm without ENE, 0.2–3 cm with ENE and > 3 cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. Conclusions: Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this study is to assess the impact of extrathyroidal autoimmune diseases (ADs) on the clinical characteristics and efficacy of iodine‐131 (131I) therapy in patients with differentiated thyroid cancer (DTC). Methods Patients with DTC who were received 131I therapy simultaneously were classified into the combination group (n = 35) and noncombination group (n = 146) depending on the presence of ADs. The clinical characteristics, such as gender, age, tumor lesions, lymph node metastasis, distant metastasis, 131I therapy efficacy, and use of levothyroxine, were compared between the two groups. Statistical analysis was conducted using SPSS 26.0 and R 4.0.3. Results There was a statistically significant difference in age between the combination and noncombination groups (t = −2.872, p .05), and there was no significant difference in the therapeutic efficacy of 131I between the two groups (p > .05). In the subgroup analysis involving patients aged great than 50.5 years, the levothyroxine/weight (µg/kg) was increased in the combination group, and the difference was statistically significant (p

IntroductionRadioactive iodine (RAI) has been utilized for nearly 80 years in treating both hyperthyroidism and thyroid cancer, and it continues to play a central role in the management of differentiated thyroid cancer (DTC) today. Recently, the use of RAI therapy for indolent, low-risk DTC has generated considerable debate. This case-control study evaluated the therapeutic response in DTC patients, comparing outcomes between those who received RAI therapy and those who did not.MethodsThe study included individuals diagnosed with either indolent or aggressive histological types of DTC who either underwent RAI therapy or did not. For each patient, information regarding demographics (age, sex, background), clinical data, laboratory parameters, pathological exam, history of RAI therapy, thyroid ultrasound findings, and loco-regional or distant metastasis was extracted. All group comparisons were made using a two-sided test at an α level of 5%.ResultsOut of 104 patients diagnosed with DTC, 76 met the inclusion criteria and were subsequently divided into two primary groups based on their history of RAI ablation. The majority of patients underwent RAI therapy (76.3%). Most patients had a good biochemical (68.4%, p = 0.246) and structural control (72.4%, p = 0.366), without a significant difference between the two groups. RAI therapy significantly protected against incomplete biochemical control in the overall population (p = 0.019) and in patients with histological indolent DTC (p = 0.030). Predictive factors for incomplete biochemical control included male sex (p = 0.008) and incomplete structural control (p = 0.002) across all patients, regardless of the histological type.DiscussionsWhile RAI therapy has traditionally been used to manage DTC, our study found no significant difference in biochemical and structural responses between patients who received RAI therapy and those who did not. However, RAI therapy emerged as a protective factor against incomplete biochemical control, even in histological indolent DTC cases. These findings suggest that while RAI therapy may not be universally necessary, it could be beneficial in reducing the risk of biochemical recurrence in select patient subgroups, such as those with incomplete structural control or male patients. Thus, a personalized approach to RAI therapy, tailored to individual risk factors, may improve patient outcomes without overtreatment.

BackgroundDifferentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC.MethodsWe conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes.ResultsAfter the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)].ConclusionsDTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.

Aims: Age is a major risk factor for differentiated thyroid cancer (DTC); however, the mechanisms underlying aging-regulated progression of DTC remains unclear. Methods: Based on multi-omics data (transcriptional files, somatic mutation files, methylation files) derived from the TCGA database, we comprehensively investigated the genomic and biological features associated with aging in patients with DTC. Results: We confirmed that age was an independent risk factor for overall survival and progression-free survival of patients with DTC, and confirmed that 55 years of age (adopted in the 8th AJCC staging system) is an appropriate cutoff for patients with DTC rather than 45 years (adopted in the 7th AJCC staging system). Using 55 years as the cutoff, we demonstrated DNA methylation-driven transcriptional regulation during aging, and identified the landscape of somatic mutations in young and old patients with DTC along with two aging-related mutations: TTN and EIF1AX. Subsequently, we investigated the infiltration of immune cells in DTC, and found that old patients exhibited decreased CD8+ T cells infiltration with lower cytotoxicity. Finally, we constructed a prognosis prediction model based on three age-related genes (PTK2B, E2F1, and GHR) that showed satisfactory performance in predicting patients prognosis. Conclusions: We comprehensively investigated the complex interplay between age and biological features of DTC, which may provide new insights into the role of aging in DTC.

Objective: The treatment landscape for thyroid cancers has changed rapidly with the availability of kinase inhibitors against VEGFR, BRAF, MEK, NTRK, and RET. We provide an up-to-date review of the role of kinase inhibitors in thyroid cancer and discuss upcoming trials. Design & Methods: A comprehensive review of the available literature describing kinase inhibitors in thyroid cancer was performed. Results and Conclusions: Kinase inhibitors have become the standard of care for patients with metastatic radioactive iodine-refractory thyroid cancer. Short-term treatment can re-sensitize differentiated thyroid cancer to radioactive iodine, thereby potentially improving outcomes and sparing toxicities associated with the long-term use of kinase inhibitors. The approval of cabozantinib as salvage therapy for progressive radioactive iodine-refractory differentiated thyroid cancer following failure with sorafenib or lenvatinib adds to the available armamentarium of active agents. Vandetanib and cabozantinib have become mainstay treatments for metastatic medullary thyroid cancer regardless of RET mutation status. Selpercatinib and pralsetinib, potent and selective receptor kinase inhibitors with activity against RET, have revolutionized the treatment paradigm for medullary thyroid cancers and other cancers with driver mutations in RET. Dabrafenib plus trametinib for BRAF mutated anaplastic thyroid cancer provides an effective treatment option for this aggressive cancer with a dismal prognosis. In order to design the next generation of agents for thyroid cancer, fut ure efforts will need to focus on developing a better understanding of the mechanisms of resistance to kinase inhibition including bypass signaling and escape mutations.

Proteinuria has been described as a major on-target adverse event of lenvatinib, although its long-term impact on renal function and clinical outcomes remains unclear. We conducted a retrospective observational study to assess renal function and prognosis in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) receiving lenvatinib. Overall, 70 patients with RR-DTC treated with lenvatinib were enrolled. When proteinuria was observed, the dose and schedule of lenvatinib were adjusted to achieve a urine protein-to-creatinine ratio (UPCR) of less than 3.5 g/gCre according to the study protocols of recent pivotal trials. In total, 50 (71%) and 25 (36%) patients presented with any-grade and grade 3 proteinuria, respectively. Multivariate analysis revealed that age [>65; odds ratio (OR) 8.24, 95% confidence interval (CI) 1.74–39.00, p < 0.01], history of diabetes mellitus (OR 7.79, 95% CI 1.31–46.20, p = 0.02), and hypertension (OR 4.07, 95% CI 1.22–13.60, p = 0.02) were significantly associated with the development of grade 3 proteinuria. Overall, the median estimating glomerular filtration rate (eGFR) gradually decreased every 3 months during treatment. However, no significant deterioration in eGFR was observed in patients with grade 3 proteinuria compared with patients with grades 0–2 proteinuria until 48 months. Patients who developed proteinuria had better survival outcomes than those without proteinuria. In conclusion, the proteinuria grade was not significantly associated with decreased eGFR under UPCR monitoring in our study. Therefore, lenvatinib can carefully be continued targeting UPCR of less than 3.5 g/gCre.

Objective(s): In systemic radionuclide therapy such as radioiodine (I-131) for differentiated thyroid cancer, post-therapy dosimetry is essential to verify pre-therapy predictions, which in turn informs the next treatment. However, post-therapy multi-time point dosimetry is resource intensive and unfeasible in many institutions. We devised a schema of rapid predictive dosimetry by circumventing post-First Strike multi-time point dosimetry with carefully assigned gestalt values of predicted kinetics to personalise the Second Strike prescription.Methods: Verification is performed after the First Strike. Patient-specific time-activity curve is plotted from serial measurements of whole body exposure rates to obtain its decay constant; its inverse is the whole body Time Integrated Activity Coefficient (TIAC). The percentage of whole body TIAC attributed to blood is carefully assigned by gestalt based on population kinetics tabulated in Part 1, adjusted by any metastasis on I-131 whole body scintigraphy. Marrow absorbed dose is calculated by EANM formularism. Lung safety threshold at 48h post-therapy is linearly scaled by height, where the patient’s risk of lung radiotoxicity is revealed from the whole body time-activity curve value at 48h. Predictive prescription for the second I-131 fraction (Second Strike) is by careful gestalt assessment based on predicted kinetics, remaining marrow and lung tolerance, marrow dose rate constraint per fraction (0.265 Gy/h), local regulatory and facility requirements in relation to radiation protection. Tumour dosimetry is obviated under the assumption of severe tumour absorbed dose heterogeneity. The final prescription for the Second Strike is usually the lowest I-131 activity amongst all clinical, dosimetric and regulatory constraints.Results: This schema is incorporated into a Predictive Calculator spreadsheet for rapid predictive dosimetry, and is freely available. Calculations may be completed within minutes to generate personalised predictive prescriptions, making it feasible for routine clinical implementation.Conclusion: Our innovative schema of rapid verification and predictive dosimetry bridges the technological gap between empiric vs theranostic prescription to help institutions modernise. Its expeditious design makes this schema feasible to be integrated into the routine clinical workflow. Its predictive estimates provide invaluable dosimetric insight to inform the next I-131 fraction, allowing every prescription to be scientifically rationalised and personalised according to individual circumstances.

Background: Ultrasound-guided fine needle aspiration thyroglobulin (FNA-Tg) is recommended for the diagnosis of lymph node metastasis (LNM) in differentiated thyroid cancer (DTC), but its optimal cutoff value remains controversial, and the effect of potential influencing factors on FNA-Tg levels is unclear. Method: In this study, a retrospective analysis was conducted on 281 patients diagnosed with DTC, encompassing 333 lymph nodes. We analyze the optimal cutoff value and diagnostic efficacy of FNA-Tg, while also evaluating the potential influence of various factors on FNA-Tg. Results: For FNA-Tg, the optimal cutoff value was 16.1 ng/mL (area under the curve (AUC)= 0.942). The optimal cutoff value for FNA-Tg/sTg was 1.42 (AUC = 0.933). The AUC for FNA combined with FNA-Tg yielded the highest value compared to other combined diagnostic methods (AUC = 0.955). It has been found that serum thyroglobulin (sTg) is positively correlated with FNA-Tg (Rs = 0.318), while serum thyroglobulin antibodies (sTgAb) is negatively correlated with FNA-Tg (Rs = -0.147). In cases where the TNM stage indicated N1b, the presence of large or high volume lymph node metastasis(HVLNM), lymph node lateralization/suspicion (L/S) ratio ≤ 2, ultrasound findings indicating lymph node liquefaction, calcification, and increased blood flow, patients with coexisting Hashimoto’s thyroiditis (HT), a tumor size ≥10 mm, and postoperative pathology confirming invasion of the thyroid capsule, higher levels of FNA-Tg were observed. However, the subgroup classification of DTC and the presence or absence of thyroid tissue did not demonstrate any significant impact on the levels of FNA-Tg. Conclusion: The findings of this study indicate that the utilization of FNA in conjunction with FNA-Tg is a crucial approach for detecting LNM in DTC. TNM stage indicated N1b, the presence of HVLNM, the presence of HT, lymph node L/ S ratio, liquefaction, calcification, tumor diameter, sTg and sTgAb are factors that can impact FNA-Tg levels.In the context of clinical application, it is imperative to individualize the use of FNA-Tg. [ABSTRACT FROM AUTHOR]