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Context Serum thyroglobulin (Tg) measured by immunometric assay (IMA) is prone to underestimation due to Tg autoantibody (TgAb) interference, often prompting reflex Tg measurement by liquid chromatography/tandem mass spectrometry (MS) or radioimmunoassay (RIA). Objective IMA, MS, and RIA methodologies were used to measure serum Tg in TgAb-negative (TgAb−) and TgAb-positive (TgAb+) patients with either distant metastatic differentiated thyroid cancer (DTC) or hyperthyroidism (HY)—patients in whom a detectable serum Tg would be expected. Results When TgAb was absent , all methodologies detected Tg in the sera of all DTC and HY patients and reported appropriate Tg trends and treatment responses for DTC patients with progressive distant metastatic disease, albeit with high between-method variability (> 30% coefficient of variability). When TgAb was present , all methodologies reported lower serum Tg levels for both DTC and HY groups vs their respective TgAb− group. No Tg was detected by IMA or MS in ∼50% TgAb+ DTC patients (6% had no Tg detected by RIA). Surprisingly, 5% of TgAb+ HY patients also had no Tg detected by IMA or MS. The inverse log TgAb/log Tg correlations seen for the TgAb+ HY patient group with all methods suggested the presence of a TgAb-associated serum Tg-lowering effect. Conclusion (i) Between-method Tg variability necessitates method continuity when monitoring the Tg trends of TgAb− DTC patients. (ii) The presence and concentration of TgAb appeared to have a lowering effect on serum Tg measured by all methodologies (IMA, MS, and RIA). (iii) Since the reliability of Tg measured in the presence of TgAb is often uncertain, the TgAb trend (measured by the same method) may be a useful surrogate DTC tumor marker. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions 124‐iodine (124I) is used for positron emission tomography (PET) diagnostics and therapy planning in patients with differentiated thyroid cancer (DTC). Small lesion sizes (<10 mm) and low 124I uptake are challenging conditions for the detection of DTC lymph node lesions.The aim of this study was to systematically investigate the lesion detectability and quantification performance under clinically challenging imaging conditions using non‐time‐of‐flight (TOF) PET/magnetic resonance imaging (MRI) in the clinical context of radionuclide therapy planning of DTC patients.PET/MR measurements were performed on the Siemens Biograph mMR using a small lesion NEMA‐like phantom (six glass spheres, diameters 3.7–9.7 mm). 60 min list‐mode data were acquired for nine activity concentrations (AC) ranging from 25 kBq/mL to 0.25 kBq/mL using a sphere‐to‐background ratio of 20:1. PET list‐mode data were divided into five timeframes (60, 30, 16, 8, and 4 min) and reconstructed using either ordered‐subsets expectation maximization (OSEM) or OSEM+ point spread function (PSF) algorithm. For all reconstructions, the smallest detectable sphere size was investigated in a human observer study. Partial volume effect (PVE) corrected PET images (contour and oversize‐based approach) were analyzed considering a ± 30% deviation range between imaged and true AC as acceptable. Clinical data of eight DTC patients with small lymph node lesions were evaluated to assess agreement between the PVE correction approaches.Longer PET acquisition times, higher ACs, and PSF reconstructions resulted in improved PET image quality and overall improved lesion detectability. The smallest 3.7 mm sphere was only visible under the best imaging conditions. Using a typical clinical 124I whole‐body PET/MRI protocol with an acquisition time of 8 min using OSEM reconstructions, all lesions of ≥ 6.5 mm in diameter could be detected and the quantification provided reliable results approximately above 5.0 kBq/mL. An accurate quantification of ACs in the 4.8 mm sphere was not feasible in this study. In the clinical evaluation of 10 lesions, a good agreement between oversize‐ and contour‐based PVE corrections was observed (<15% deviation).The results showed that a reliable quantification of 124I uptake with PET/MRI is feasible and, therefore, could be used to perform radioiodine pre‐therapy lesion dosimetry and individualized therapy planning in DTC patients. [ABSTRACT FROM AUTHOR]

Background: [18F]FDG PET/CT has been widely used as a diagnostic tool in detection and localization of recurrent non-avid radioiodine lesions in post-operative differentiated thyroid cancer (DTC) patients with elevated serum thyroglobulin but negative radioiodine whole-body scan (TENIS) syndrome. The aim of our study was to evaluate the role of [18F]FDG PET/CT in prediction on outcomes of these DTC patients. Methods: Post-operative DTC patients with TENIS syndrome were collected in the department of nuclear medicine, Hospital 108 from 2019 to 2023. Patients underwent [18F]FDG PET/CT with standard protocol following EANM guideline for tumor imaging version 2.0. The qualitative [18F]FDG PET/CT imaging characteristics were classified into three categories: (i) negative [18F]FDG PET/CT, (ii) minimal [18F]FDG PET/CT volume of lesions, (iii) extensive [18F]FDG PET/CT volume of lesions. Progression-free survival (PFS) and overall survival (OS) were the end point of the study. The prognosis of qualitative [18F]FDG PET/CT in predicting PFS and OS was illustrated by Kaplan–Meier survival analysis. The independent factors predicting PFS and OS were determined by univariate and multivariate analysis using logistic regression. Results: There were 164 consecutive patients, 51.2% female and 48.8% female. The most common histopathological type was papillary accounting for 91.5%. The median time of follow-up was 33.3 months, (range 6.57 – 82.5). There was 70 (36.6%) progressions and 12 (7.35%) deaths. Negative [18F]FDG PET/CT uptake patients had median PFS with median 57.1 months which was higher than that of minimal category (46.2 months), and extensive category (37.6 months) (p < 0,001). 1-year OS and 5-year OS in extensive PET/CT category was 97.8% and 86.2% respectively which were significantly lower than that of negative and minimal categories (p = 0.053). In multivariate analysis, age at the time of diagnosis, pulmonary, bone metastases and extensive [18F]FDG PET/CT volume of lesions were the independent factor predicting PFS. Bone metastasis was only the factor could predict OS in multivariate analysis. Conclusions: The minimal and negative [18F]FDG PET/CT categories had better prognosis than extensive category in PFS and OS. Extensive [18F]FDG PET/CT category was an independent factor for predicting PFS. Bone metastasis was only the independent factor that could predict both PFS and OS. [ABSTRACT FROM AUTHOR]

Introduction: Forkhead 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. Methods: A 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. Results: After 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. Conclusion: FOXE1 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. [ABSTRACT FROM AUTHOR]

Introduction: Plasma 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 methods: This 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. Results: Median 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. Discussion: Based on the results of this study, plasma cfDNA levels did not significantly predict disease status in patients with DTC in the post-operative setting. [ABSTRACT FROM AUTHOR]

Background: Limited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC). Methods: In 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. Results: In 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. Conclusions: In 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. [ABSTRACT FROM AUTHOR]

Despite the generally good prognosis of differentiated thyroid cancer (DTC), impairments in health-related quality of life (HRQoL) remain a major concern in these patients. This study examined the patterns and predictors of change in mental and physical HRQoL in DTC survivors following radiotherapy ablation. Two hundred patients with DTC who received radiotherapy ablation in southern Taiwan between 2015 and 2018 were interviewed using the Taiwan version of the 36-item Short-form Health Survey (SF-36), the Taiwanese Depression Questionnaire (TDQ), and the Hamilton Rating Scale for Anxiety (HAM-A) at baseline and after 24 and 48 weeks of treatment. The demographic characteristics, thyroid-related factors, recombinant human thyroid-stimulating hormone (rhTSH), and serum calcium level were also collected. Improvements in both mental and physical HRQoL were noted over the first 24 weeks following radiotherapy ablation. Between 24 and 48 weeks, mental HRQoL was increasing, whereas physical HRQoL decreased. Higher levels of anxiety and pain predicted both poor physical and mental HRQoL. Further, higher levels of depression predicted poor mental HRQoL. Additionally, factors such as low income, rhTSH use, elevated TSH levels, low free T4, and higher physical HRQoL were associated with poorer mental HRQoL during the follow-up period. The early detection and intervention of depression, anxiety, and pain should be the objective for programs aiming to improve HRQoL. [ABSTRACT FROM AUTHOR]

Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients' selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., 123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Pregnant women with a diagnosis of differentiated thyroid cancer (DTC) were potentially high-risk but largely ignored study population. We aimed to explore whether gestational thyrotropin levels were associated with progression of DTC. Methods: We conducted a retrospective cohort study at Peking University Third Hospital in Beijing, China from January 2012 to December 2022. We included pregnant women with a pre-pregnancy DTC managed by active surveillance (under-surveillance DTC) or surgical treatment (after-surgery DTC). Dynamic changes of gestational thyrotropin levels across multiple time points were characterized by both statistical (average level, change instability, longitudinal trajectory) and clinical (thyroid dysfunction, thyrotropin suppression, and achievement of thyrotropin suppression target) indicators. Outcomes were clinician-validated progression of DTC, measured separately for patients under surveillance (tumor enlargement or lymph node metastasis) and those after surgery (≥ 3 mm growth in the size of existing metastatic foci, development of new lymph node metastases, ≥ 2 mm growth in the size of existing cancer foci in the contralateral thyroid, or biochemical progression). Results: Among 43 and 118 patients with under-surveillance and after-surgery DTC, we observed no evidence of associations between any of the quantitative or clinical indicators of gestational thyrotropin levels and progression-free survival, after a median of 2.63 (IQR: 0.90-4.73) and 4.22 (2.53-6.02) year follow-up, respectively (all P values > 0.05). Conclusions: Gestational thyrotropin levels appeared to play a minor role in the progression of under-surveillance or after-surgery DTC. Clinicians might focus on the risk of adverse pregnancy outcomes when optimizing thyrotropin levels for pregnant women with a diagnosis of DTC. [ABSTRACT FROM AUTHOR]

Background The optimal cumulative activity (CA) of I-131 therapy for patients with metastatic differentiated thyroid cancer (mDTC) remains contentious. This study aimed to determine the maximum CA of I-131 that could be administered without a significant increase in adverse events (AEs) by analyzing a long-term cohort of patients. Methods Data from patients with mDTC treated with I-131 therapy and followed for at least 2 years from 1967 to 2019 were reviewed. Patients were categorized into 3 groups based on the received CA: group A (≤600 mCi), group B (>600-1000 mCi), and group C (>1000 mCi). The study assessed long-term AEs and survival outcomes. Results The study included 671 adult patients with mDTC (mean age, 48 years; range, 19-81) with a median follow-up of 122 months (interquartile range: 82-180). Group A, group B, and group C comprised 269 (40.0%), 212 (31.6%), and 190 (28.4%) patients, respectively. Ten-year survival rates were 72%, 42.7%, and 29% in groups A, B, and C, respectively. A total of 40/671 (6%) AEs were observed in 38 patients: 3 (1.1%), 12 (5.7%), and 25 (13.2%) in groups A, B, and C, respectively. Five patients developed second primary malignancy: 3 in group A and 1 each in group B and C. However, CA >1000 mCi of I-131 was associated with significant increase in bone marrow suppression, decreased pulmonary function, and xerostomia (P <.001). Conclusion The study suggests that a maximum CA of up to 1000 mCi strikes a favorable balance between keeping AEs low and benefiting a subset of patients with extensive metastases showing intense I-131 concentration. [ABSTRACT FROM AUTHOR]

Introduction: Radioactive 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. Methods: The 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 a level of 5%. Results: Out 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. Discussions: While 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. [ABSTRACT FROM AUTHOR]

It is well established that patients with the most differentiated thyroid cancers have a good prognosis, whereas when the disease develops into radio-iodine refractory thyroid cancer (RAIR) their prognosis is poor and the 10-year survival rate is low. At present, the therapeutic methods for RAIR are limited and have low efficacy. As a consequence, several models have been developed for predicting RAIR. The aim of this review was to describe recent developments regarding the factors that influence and predict the occurrence of RAIR. Many variables including demographic characteristics, tumor clinicopathology, serology changes, disease characteristics, and PET/CT results have been shown to be independent factors that influence the development of RAIR. The cut-off value derived from multivariate prediction models therefore effectively predicts the onset of RAIR. However, the current models for predicting RAIR were obtained through retrospective studies, and the prospective prediction studies are needed in the future to confirm their validity. [ABSTRACT FROM AUTHOR]

Introduction: The optimal strategy for differentiated thyroid cancer (DTC) patients treated with radioiodine (RAI) following thyroidectomy remains controversial. Multi-centre clinical studies are essential to identify strategies to improve patient outcomes while minimising treatment-induced toxicity. Materials and Methods: The INSPIRE clinical trial (ClinicalTrials.gov Identifier: NCT04391244) aims to investigate patient-specific dosimetry for DTC patients and to determine the range of absorbed doses delivered to target and nontarget tissues and their relationship with treatment outcome and toxicity. Results: We report here initial results of the first 30 patients enrolled onto the INSPIRE trial. A large range of absorbed doses are observed for both thyroid remnants and salivary glands, with median values of 4.8 Gy (Range 0.2 -- 242 Gy) and 0.3 Gy (Range 0.1 to 1.7 Gy), respectively. Discussion: The preliminary study results are encouraging and could help to improve our understanding of absorbed doses to thyroid remnants and normal organs following RAI therapy. Such knowledge could potentially enable patient specific treatment planning with improved clinical outcomes and quality-of-life of patients. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp's role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAFV600E (9/143, 6.3%) than those with both BRAFV600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAFV600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAFV600E alone (33.3%, 3/9). Only one patient with both BRAFV600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAFV600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAFV600E alone (p < 0.01). Our findings suggest that molecular testing for TERTp and other mutations like BRAFV600E may inform early diagnosis, prognosis, and treatment strategies before progression to RAIR-DTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-iodine avid differentiated thyroid cancer (DTC) may be a diagnostic problem, especially in patients with an indeterminate response to treatment (i.e., with thyroglobulin (Tg) concentration in the range of 1–10 ng/mL). PET/CT with [18F]FDG may be a useful technique for visualizing non-iodine avid DTC lesions. Presented study assessed the usefulness of using exogenous stimulation with recombinant human TSH (rhTSH) before PET/CT with [18F]FDG in detecting non-iodine avid foci of DTC in patients with elevated sTg and negative 131I WBS and the usefulness of Tg concentration in predicting a positive result of [18F]FDG PET/CT in this type of patients and to determine the optimal Tg cut-off point for obtaining a positive [18F]FDG PET/CT result. In a retrospective analysis including 73 patients with DTC suspected of having non-iodine avid recurrence or metastases there was no effect of rhTSH stimulation on the sensitivity and specificity of PET/CT, but a positive impact on the number of lesions visible in the examination was observed. Moreover, rhTSH stimulation allowed for visualization of non-iodine avid lesions with lower Tg concentration. Introduction: Non-iodine avid metastases of differentiated thyroid cancer (DTC) can be found using PET/CT with a fluorine-18-labeled glucose analog ([18F]FDG). There are ongoing discussions on the appropriateness of using exogenous thyrotropin (TSH) stimulation before this examination. Material and Methods: In a retrospective study, 73 PET/CT scans with [18F]FDG performed after exogenous stimulation with recombinant human TSH (rhTSH) and without such stimulation were analyzed. All analyzed patients were suspected of having non-iodine-avid foci of DTC. Results: The stimulation with rhTSH before the PET/CT did not affect the percentage of positive results: 37.5% (18/48) with rhTSH and 40% (10/25) without rhTSH (p = 0.83). The analysis of the ROC curves established the cut-off thyroglobulin point for a positive PET/CT result separately for both subgroups. There was no statistically significant difference between obtaining a positive PET/CT result and the baseline thyroglobulin concentration (both stimulated and unstimulated). The exogenous stimulation of TSH prior to the PET/CT had no effect on the [18F]FDG uptake in the PET/CT lesions. Conclusions: PET/CT with [18F]FDG remains a useful method for the diagnosis of non-iodine-avid DTC lesions; in the presented group, a positive effect of rhTSH stimulation on the number of DTC foci visible in the PET/CT was found, but without affecting its effectiveness. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BM) are the most common intracranial neoplasms in adults and are a significant cause of morbidity and mortality. The brain is an unusual site for distant metastases of thyroid cancer; indeed, the most common sites are lungs and bones. In this narrative review, we discuss about the clinical characteristics, diagnosis, and treatment options for patients with BM from differentiated thyroid cancer (DTC). Summary: BM can be discovered before initial therapy due to symptoms, but in most patients, BM is diagnosed during follow-up because of imaging performed before starting tyrosine kinase inhibitors (TKI) or due to the onset of neurological symptoms. Older male patients with follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and distant metastases may have an increased risk of developing BM. The gold standard for detection of BM is magnetic resonance imaging with contrast agent administration, which is superior to contrast-enhanced computed tomography. The treatment strategies for patients with BM from DTC remain controversial. Patients with poor performance status are candidates for palliative and supportive care. Neurosurgery is usually reserved for cases where symptoms persist despite medical treatment, especially in patients with favorable prognostic factors and larger lesions. It should also be considered for patients with a single BM in a surgically accessible location, particularly if the primary disease is controlled without other systemic metastases. Additionally, stereotactic radiosurgery (SRS) may be the preferred option for treating small lesions, especially those in inaccessible areas of the brain or when surgery is not advisable. Whole brain radiotherapy is less frequently used in treating these patients due to its potential side effects and the debated effectiveness. Therefore, it is typically reserved for cases involving multiple BM that are too large for SRS. TKIs are effective in patients with progressive radioiodine-refractory thyroid cancer and multiple metastases. Conclusions: Although routine screening for BM is not recommended, older male patients with FTC or PDTC and distant metastases may be at higher risk and should be carefully evaluated for BM. According to current data, patients who are suitable for neurosurgery seem to have the highest survival benefit, while SRS may be appropriate for selected patient. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid carcinoma (DTC) in children is uncommon; clinical presentation over recent decades is incompletely characterized. Methods: This retrospective cohort study analyzed demographic and disease characteristics of consecutive juveniles with DTC treated from 1970 to 2015 at Poland's largest pediatric DTC referral center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, who had available records. Sex, age, histopathological characteristics, and DTC stage were documented. We aimed to identify changes in these variables over time and independent risk factors for lymph node or distant metastases. Trends in these variables were assessed using the Cochran–Armitage test and Spearman correlation. Multivariable logistic regression was performed to identify risk factors associated with lymph node or distant metastases. Results: 475 of 479 patients (99.2%) were included in the analysis; roughly half were age ≥15 years, 10%, <10 years. Papillary thyroid carcinoma (PTC) represented 88% of cases and follicular thyroid carcinoma (FTC) 11%. Tumors ≤2 cm constituted 56% of cases with relevant data; those >4 cm accounted for 12%. Multifocality was observed in 37% and extrathyroidal invasion in 22%. Lymph node metastases were noted in 59% and distant metastases in 16%. Over the observation period, significant trends among new cases included: increased proportion of adolescents >15 years; increased frequency of tumors ≤2 cm, decreased multifocality rates, and increased proportion of PTC versus FTC. Extrathyroidal invasion rates remained appreciable throughout, ranging from 17 to 28% during the 5-year study subperiods after 1990. Lymph node metastases significantly increased in frequency in the central neck, remaining consistently common in lateral sites; presence of distant metastases significantly decreased. In multivariable analysis, multifocality, extrathyroidal invasion, and tumor size were independently associated with lateral lymph node metastases and multifocality, larger tumor size, and N1b metastases with distant spread. Conclusions: Our observations of a rising proportion of diagnoses in adolescence, reductions in primary tumor size, and decreased frequency of multifocality and distant metastases may reflect increased detection of patients with less aggressive DTC at earlier disease stages. Nonetheless, we found persistently substantial rates of locoregionally advanced disease features (multifocality, extrathyroidal invasion, and lymph node metastases), which multivariable analyses suggested have significant associations with lateral lymph node and/or distant metastases. [ABSTRACT FROM AUTHOR]

Background: Treatment options for patients with differentiated thyroid cancer (DTC) who experience disease progression on lenvatinib treatment are limited. Although dose escalation of treatment with tyrosine kinase inhibitors at disease progression has been reported across cancer types, clinical significance in patients with DTC has not been investigated. Methods: We retrospectively reviewed patients with DTC who experienced disease progression on lenvatinib treatment from September 2011 to June 2022. We compared subjects who received dose-escalation treatment with standard treatment of termination at the time of initial disease progression. The escalated dose was decided by referencing to the previous effective and tolerated dose. Results: Thirty-three patients were identified, 15 with dose escalation and 18 with lenvatinib termination. In both groups, the starting dose of lenvatinib was 24 mg/day, and the median dose at initial disease progression was 10 mg/day. In the former, the median dose escalation was 6 mg/day (range: 4–12). Objective response rate, clinical benefit rate by escalation, and median treatment duration of the dose-escalation phase were 13.3%, 73.3%, and 9.9 months (95% confidence interval [CI] 5.71–27.6), respectively. Median overall survival from initial disease progression was significantly longer in the dose-escalation group (median OS: 20.4 months [95% CI 7.0–NA] vs. 3.9 months [95% CI 1.7–7.9], log-rank p-value; 0.0004, hazard ratio; 0.22 [95% CI 0.09–0.55]). There were no grade 5 adverse events, and one patient discontinued due to a grade 3 lung abscess. Conclusion: The dose-escalation strategy appears to be a safe and effective treatment option after disease progression in patients treated with lenvatinib for DTC. [ABSTRACT FROM AUTHOR]

The role of lactate dehydrogenase A (LDHA) expression in differentiated thyroid cancer (DTC), especially in radioiodine-refractory DTC, remains unclear. The aim of this study was to analyse the relationships and the prognostic value of LDHA, glycolysis, and radioactive iodine (RAI) avidity in DTC. DTC patients who underwent 18F-FDG PET/CT and subsequent total thyroidectomy or metastasectomy were enroled. The expression levels of LDHA, glucose transporters (Glut) and Ki67 proteins in tumour tissue were measured using immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of 18F-FDG PET/CT were measured. A radioiodine whole body scan was used to determine lesion radioiodine avidity. 69 patients with DTC were enroled in this study, including 37 women (53.6%) and 32 men (46.4%), with a median age of 52 years (11 to 77 years). Regarding the pathological category, papillary thyroid cancer was documented in 50 patients (72.5%), while follicular and poorly differentiated thyroid cancer were found in 12 patients (17.4%) and seven patients (10.1%), respectively. Distant metastases were observed in 27 (39.1%) patients; 34 (49.3%) were classified as stage I, 16 (23.2%) as stage II, and 3 (4.3%) and 16 (23.2%) patients in stages III and IV, respectively. LDHA expression levels were correlated with Glut3 expression levels (r = 0.395, P = 0.003) and SUVmax (r = 0.408, P = 0.002). The median LDHA expression and lesion SUVmax of the RAI avidity group were lower than those of the non-RAI avidity group (200 vs. 285, P = 0.036; 3.06 vs. 8.38, P = 0.038, respectively). Elevated SUVmax (P = 0.004), MTV (P = 0.014), TLG (P = 0.001) and LDHA expression (P = 0.048) led to shorter time to progression (TTP); Cox regression analysis revealed that TLG (HR: 4.773, P = 0.047) was an independent prognostic factor of TTP. Elevated LDHA is correlated with increased glucose metabolism, decreased radioiodine avidity, and accelerated disease progression. Moreover, 18F-FDG PET/CT acting as "in vivo pathology" is an excellent predictor of DTC prognosis. [ABSTRACT FROM AUTHOR]

Purpose: There is a tendency to use data generated for adults in the management of pediatric Differentiated Thyroid Carcinoma, neglecting the clinical peculiarities of this condition in childhood. This study aimed to assess and compare the clinical-epidemiological characteristics and their significance in the evolution of thyroid carcinoma diagnosed in childhood across different age groups. Methods: Seventy-seven patients diagnosed with Differentiated Thyroid Carcinoma (DTC) up to 21 years old were selected and divided into different age groups: up to 10 years, 11 to 18 years, and 19 to 21 years old. Clinical-epidemiological data and their influence in the disease progression were analyzed and compared across age groups. Results: Patients diagnosed below 10 years of age were associated with tumors showing extrathyroidal extension, metastasis in regional lymph nodes, higher levels of stimulated thyroglobulin in the diagnostic iodine-131 whole-body scan (WBS), and under TSH suppression in the last assessment. Additionally, pulmonary metastasis were associated in both diagnostic and post-radioiodine dose WBSs in these younger patients. Analysis of findings in the post-radioiodine therapy WBS revealed significant differences between all age groups (p = 0.0029). The time of diagnosis was identified as a factor associated with an excellent response in subgroups up to 18 years and up to 21 years. No factors associated with dynamic responses over the 1st, 3rd and 5th years of follow-up and the persistence/recurrence of the disease were identified in the subgroup up to 18 years. In the subgroup up to 21 years, having an incomplete structural response in the 3rd year of follow-up increased the chances of recurrent or persistent response by 5.5 times, and by 32.6 times if found in the 5th year of follow-up. Conclusions: Younger patients exhibited more aggressive tumor characteristics and underwent more rigorous treatment. However, treatment response and disease status in the last assessment, whether free or recurrent/persistence, were similar when comparing the age groups of 11 to 18 and 19 to 21 years. Nonetheless, responses obtained in the 3rd and 5th years post-treatment emerged as factors associated with the persistence/recurrence of the disease in the last assessment in the age group up to 21 years but not in patients diagnosed up to 18 years, a relevant distinction considering the tumor behavior in defining the pediatric age range in thyroid cancer. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was evaluate biochemical incomplete response (BIR) in Middle Eastern differentiated thyroid cancer (DTC), identify factors that could predict BIR before radioactive iodine (RAI) ablation and to investigate the long-term clinical outcome of DTC patient exhibiting BIR to initial therapy. Methods: We retrospectively evaluated 1286 DTCs from Middle Eastern ethnicity who underwent total thyroidectomy and RAI therapy. Demograpic and clinico-pathological factors predicting BIR were evaluated. The outcome of these patients was analyzed using primary outcome of structural disease and disease-free survival (DFS). Results: With a median follow-up of 10 years, 266 (20.7%) patients had BIR. High pre-ablation stimulated thyroglobulin (presTg), presence of lymph node metastasis, male gender and delayed initial RAI therapy (≥3 months) after thyroidectomy were significant independent predictors of BIR. Upon evaluating long-term clinical outcomes in 266 patients with BIR, we found 36.8% of patients developed structural disease. Male sex (OR = 1.56; 95% CI = 1.05–2.30; p = 0.0272) and increasing Tg after initial therapy (OR = 4.25; 95% CI = 1.93–10.82; p = 0.0001) were independent risk factors for structural disease in patients with BIR. DFS was significantly worse if both these risk factors existed concomitantly (p < 0.0001). Conclusion: To achieve the fair efficacy of RAI therapy, early prediction of BIR before RAI ablation is desirable. Our finding of the clinico-pathological factors (high presTg level, LNM, delayed RAI therapy and male gender) could serve as easy and robust early predictors of BIR. In addition, DTC patients exhibiting BIR had a high risk of structural disease and hence personalized management approach would be preferable for BIR patients to ensure best clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: Cervical lymph nodes (LN) represent the most common site of recurrence in differentiated thyroid cancer (DTC), frequently requiring repeated interventions that contribute to increase morbidity to a usually indolent disease. Data on active surveillance (AS) of nodal metastasis are limited. Therefore, we performed a systematic review and meta-analysis to evaluate AS in nodal metastasis of DTC patients. Methods: MEDLINE, EMBASE, and Cochrane databases were searched up to July 2023 for studies including DTC patients with metastatic LN who were followed up with AS. The primary outcome was disease progression, according to the study's definition. Additional outcomes were LN enlargement ≥3 mm, occurrence of new cervical metastasis, and conversion from AS to surgical treatment. Results: The search identified 375 studies and seven were included, comprising 486 patients with metastatic nodal DTC. Most were female (69.5%) and had papillary thyroid cancer (99.8%). The mean AS follow-up ranged from 28–86 months. Following each study's definition of progression, the pooled incidence was 28% [95% confidence interval (CI), 20–37%]. The pooled incidence of LN growth ≥ 3 mm was 21% [95% CI, 17–25%] and the emergence of new LN sites was 19% [95% CI, 14–25%]. Combining growth of 3 mm and the emergence of new LN criteria, we found an incidence of 26% [95% CI, 20–33%]. The incidence of neck dissection during AS was 18% [95% CI, 12–26%]. Conclusions: AS seems to be a suitable strategy for selected DTC patients with small nodal disease, avoiding or postponing surgical reintervention. Prospero registration: CRD42023438293. [ABSTRACT FROM AUTHOR]

Yan Wang,1,2 Junshun Chang,1 Ben Hu,3 Suyun Yang1 1Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Academy of Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 3The Fifth Clinical Medical School of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Ben Hu; Suyun Yang, Email a917744537@163.com; wangyan86@sxmu.edu.cnPurpose: This research sought to evaluate the clinical value of systemic immune-inflammation index and systemic inflammation response index in predicting the response to radioactive iodine (RAI) therapy in individuals diagnosed with differentiated thyroid cancer.Patients and Methods: This retrospective study included 406 patients with differentiated thyroid cancer who received initial RAI therapy and follow-up from December 2019 to December 2023. Patients were divided into two groups based on imaging and serum indicators to evaluate the response to radioactive iodine treatment: the ER group (excellent response) and the non-ER group (suboptimal response). Systemic immune-inflammation index and systemic inflammation response index were calculated based on peripheral blood cell counts before treatment. Multivariable logistic regression analysis was used to assess the independent associations of these indices with the therapeutic response to radioiodine treatment. Receiver operating characteristic (ROC) curves were graphed and the area under the curve (AUC) was calculated to evaluate their predictive ability.Results: Compared to the ER group, patients in the non-ER group had significantly elevated systemic immune-inflammation index and systemic inflammation response index levels (p < 0.001). After adjusting for confounding factors, there was a significant association between these indices and the response to radioactive iodine treatment in patients with differentiated thyroid cancer. The optimal cutoff values for predicting the response to RAI treatment were 668.91 for systemic immune-inflammation index (AUC=0.692, sensitivity 58.2%, specificity 73.1%, 95% CI: 0.639– 0.745, p < 0.001) and 0.47 for systemic inflammation response index (AUC=0.664, sensitivity 85.6%, specificity 42.7%, 95% CI: 0.612– 0.717, p < 0.001).Conclusion: Systemic immune-inflammation index and systemic inflammation response index could be valuable for predicting the response to RAI treatment in individuals diagnosed with differentiated thyroid cancer. Further research is needed to explore their practical utility, and these novel inflammation markers could serve as adjunct tools in clinical practice.Keywords: systemic immune-inflammation index, systemic inflammation response index, differentiated thyroid cancer, radioactive iodine therapy

Despite the generally good prognosis of differentiated thyroid cancer (DTC), impairments in health-related quality of life (HRQoL) remain a major concern in these patients. This study examined the patterns and predictors of change in mental and physical HRQoL in DTC survivors following radiotherapy ablation. Two hundred patients with DTC who received radiotherapy ablation in southern Taiwan between 2015 and 2018 were interviewed using the Taiwan version of the 36-item Short-form Health Survey (SF-36), the Taiwanese Depression Questionnaire (TDQ), and the Hamilton Rating Scale for Anxiety (HAM-A) at baseline and after 24 and 48 weeks of treatment. The demographic characteristics, thyroid-related factors, recombinant human thyroid-stimulating hormone (rhTSH), and serum calcium level were also collected. Improvements in both mental and physical HRQoL were noted over the first 24 weeks following radiotherapy ablation. Between 24 and 48 weeks, mental HRQoL was increasing, whereas physical HRQoL decreased. Higher levels of anxiety and pain predicted both poor physical and mental HRQoL. Further, higher levels of depression predicted poor mental HRQoL. Additionally, factors such as low income, rhTSH use, elevated TSH levels, low free T4, and higher physical HRQoL were associated with poorer mental HRQoL during the follow-up period. The early detection and intervention of depression, anxiety, and pain should be the objective for programs aiming to improve HRQoL.

Background: Primary malignancies of the thyroid gland are less frequent in the first two decades of life and accounts for only 0.5-3% of all malignant neoplasms in children and adolescents.Methods: A retrospective analysis was undertaken on children less than 18 years of age who were diagnosed with thyroid malignancy from 1st June 2018 to 31st May 2022. The electronic health records were reviewed to determine patient demographics, pathological characteristics, interventions (surgery and radioactive iodine therapy [RAI]) and follow up.Results: Eighteen patients were less than 18 years of age at the time of diagnosis. Mean age at diagnosis was 14.7 years (6-18 years). Majority were females and in post pubertal age group. Among our cohort 83.4% had stage 1 disease, whereas 16.6% had stage II disease. Lung involvement was noted in 16.6%. Risk stratification revealed that 44.6% of the children were in the high-risk group and 38.8% in the intermediate- risk group. Fifteen patients (83.3%) underwent I-131 therapy. Follow up period ranged from 2-51.7 months with a median follow up period of 22.15 months. Complete remission was noted in 15 patients (83.3%). Out of the children with metastatic lung disease, 1 had progressive disease, 2 had stable disease. Overall survival was 100%.Conclusion: Majority of our children in our retrospective data presented with nodal and distant metastasis. With the current advances in the treatment of thyroid malignancies, a good survival was noted even in children with pulmonary metastasis.

Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III–V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin–angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

Abstract Background Despite the high cure rate of differentiated thyroid cancer (DTC), patients endure side effects from treatment and psychological distress, impacting their quality of life. The potential of mobile health (mHealth) interventions to address these issues remains unexplored. The purpose of this study is to develop an mHealth intervention based on the Multi-Theoretical Model of Health Behavior Change (MTM) and evaluate its impact on reducing anxiety, depression, fear of cancer progression, and enhancing quality of life in DTC patients. Methods A single-blind, single-center, prospective, randomized controlled trial was conducted. One hundred and eleven consecutive DTC patients from Harbin Medical University’s Fourth Hospital were enrolled from March 2023 to March 2024. Participants were randomized into a control group and an intervention group that received a 3-month mHealth intervention based on MTM theory. Outcomes were assessed using web-based questionnaires at baseline and conclusion. Results One hundred four patients with DTC completed the study, with 7 lost to follow-up (6.3%). The intervention group experienced a significant drop in PHQ-4 scores post-MTM-mHealth intervention (P

Abstract Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAF V600E (9/143, 6.3%) than those with both BRAF V600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAF V600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAF V600E alone (33.3%, 3/9). Only one patient with both BRAF V600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAF V600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAF V600E alone (p

Background: Noise, an unwanted variability in judgment, is ubiquitous in medicine, including in the prescription of radioactive iodine (RAI). Building upon our recently developed predictive risk model, we created an online clinical support tool to facilitate the translation of our model into clinical practice. The aim of this study is to assess the utility of an online clinical support tool to reduce noise in the treatment for patients with differentiated thyroid cancer (DTC). Methods: The tool was accessible via weblink or a QR code. Activity recommendations were applied to the calculator’s four risk categories: 0 GBq for very low risk, 1 GBq for low risk, 4 GBq for intermediate risk, and 6 GBq for high risk. The tool was applied prospectively to 103 patients who received RAI at Royal North Shore Hospital between 2021 and 2022 and retrospectively to 393 patients treated with RAI between 2017 and 2021. Results: A significant difference was observed in administered activity between the 2021–2022 and 2017–2021 cohorts in patients stratified as intermediate risk (median activity 3.95 GBq, interquartile range 2.03–4.04 vs 4 GBq, 4–4) and high risk (4.07 GBq, 3.95–5.7 vs 6 GBq, 6–6) with P-values of 0.01 and

INTRODUCTION: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence. METHODS: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. RESULTS: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]. DISCUSSION AND CONCLUSION: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.

Differentiated thyroid cancer is one of the most common malignant diseases of the endocrine system. Usually, it responds well to the standard treatment (surgery + radioiodine therapy), especially at early stages. During both treatment and dynamic observation, distant metastases are detected in 10–15 % of patients. In these cases, the patients continue treatment with radioactive iodine. If tumor cells have insufficient ability to capture and retain 131I or completely lose this ability, the effect of radioiodine therapy becomes limited and the disease progresses during therapy which leads to 5–10 % decrease in 10-year survival. The main problem in treatment of differentiated thyroid cancer is communication between radiologists in centers performing radioiodine therapy and clinical oncologists performing surgeries and observation at patient’s place of residence. For both specialists, the main goal is to identify clinical situations where early and effective treatment intervention can be beneficial without the risk of overdiagnosis and excessive treatment.The article considers common questions arising during multidisciplinary interactions with radiologists of radioiodine centers and presents concise guidelines on the observation and treatment procedures for patients with differentiated thyroid cancer.

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used and has demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Introduction: This study aimed to evaluate the clinical value of iodine-131 combined with levothyroxine sodium in the treatment of patients with differentiated thyroid cancer (DTC) after surgery. Methods: Prospective randomized controlled studies were conducted. A total of 374 DTC patients who underwent total or near-total thyroidectomy in the Department of Thyroid Surgery, Tianjin Union Medical Center and Tianjin Medical University General Hospital, from January 2019 to February 2022 were selected and divided into control group (187 cases) and observation group (187 cases) according to random number table method. The control group was treated with levothyroxine sodium after surgery, and the observation group was treated with iodine-131 on the basis of the control group. Gender, age, course of disease, tumor diameter, pathological type, TNM classification, treatment effect, thyroglobulin (Tg) levels before and after treatment, SF-36 health status questionnaires (SF-36), occurrence of adverse reactions after treatment, and recurrence rate of 1-year follow-up were compared and analyzed between the two groups. Results: There was no significant difference in baseline data between the two groups. After treatment, the effective rate of the observation group increased by 11.23% compared to the control group, with a statistically significant difference (91.98% vs. 80.75%, p < 0.05). There was no significant difference in Tg level and scores of SF-36 evaluation including physical functioning, physical problems, vitality, pain, mental health, emotional problems, social functioning, and general health perception between the two groups before surgery (p > 0.05), Tg levels and scores of SF-36 evaluation in all dimensions were significantly improved in both groups after treatment (p < 0.05), and the levels of Tg and scores of SF-36 in all dimensions in observation group were significantly better than those in control group after treatment (p < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). The recurrence rate in the observation group was 5.89% lower than that in the control group 1 year after treatment, with a statistically significant difference (2.67% vs. 8.56%, p < 0.05). Conclusions: The combination of iodine-131 and levothyroxine sodium in the postoperative treatment of DTC can improve the therapeutic effect and reduce the postoperative recurrence rate without increasing adverse reactions, which is worthy of clinical reference and promotion. [ABSTRACT FROM AUTHOR]

Background: Although patients with differentiated thyroid cancer (DTC) have a good prognosis, their long-term clinical course can influence their mental health and their health-related quality of life (HRQoL). However, few studies have evaluated the psychological factors that influence subsequent HRQoL in this population, particularly during the initial treatment stage. Methods: In this 1-month cohort study, we evaluated depressive and anxiety symptoms and HRQoL of patients with DTC and examined possible predictors of further HRQoL impairment. Results: In total, 181 patients completed questionnaires where they self-rated their psychological status (the Chinese Health Questionnaire [CHQ], Taiwanese Depression Questionnaire [TDQ]) and HRQoL (the 36-item Short Form Health Survey [SF-36]) at baseline and 1 month after radioactive iodine (RAI) therapy. Compared with the general Taiwanese population, patients with DTC reported a worse HRQoL in all dimensions of the SF-36. Multivariate regression models indicated that anxiety and depressive symptoms were inversely correlated with some dimensions (physical functioning, bodily pain, and general health perceptions for the CHQ; role limitations due to physical problems and social functioning for the TDQ). However, psychiatric follow-up and treatment history were significantly associated with physical functioning and role limitations owing to the physical problem dimensions of HRQoL. Conclusions: In conclusion, although anxiety and depressive symptoms may negatively affect certain HRQoL domains, psychiatric follow-up can improve the physical dimensions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. OBJECTIVE: To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. METHODS: A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. RESULTS: Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. CONCLUSIONS: VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients. [ABSTRACT FROM AUTHOR]

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 <.01), and the optimal cutoff value was 50.5 years. Propensity score matching was completed effectively on a total of 121 patients, using age as the matching factor, comprising 32 cases in the combination group and 80 cases in the noncombination group. The baseline demographic features of the two groups were equivalent after matching (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 <.05). Conclusion: While extrathyroidal ADs may enhance the detection of DTC among elderly women, they have no impact on the clinical characteristics of thyroid cancer or the efficacy of 131I therapy. ADs may necessitate higher per‐unit dosages of levothyroxine in patients with DTC, regardless of the clinical status. Consequently, it is not essential for nuclear medicine physicians to consider the presence of ADs when designing treatment plans for patients with DTC. [ABSTRACT FROM AUTHOR]

Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/ recurrence. Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]. Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC. [ABSTRACT FROM AUTHOR]

Purpose: Ruling out that healthy organs receive doses higher than those allowed in treatments with Iodo-131 (131I) for ablation of thyroid remnant is crucial for the radiological protection of the patient who also received the recombinant human thyroid-stimulating hormone (rhTSH). So, the investigation aimed to determine the changes in energy imparted by 131I in multiple organs due to the rhTSH in thyroid remnants and metastases of patients treated with high 131I activities (≥ 5,550 MBq). Materials and methods: Nine patients were divided into three groups (three per group); Group I included thyroid hormone withdrawal (THW) patients, while patients in groups II and III were stimulated with rhTSH. The activity and absorbed dose in regions of interest (ROIs) was quantified using the conjugated views method using gamma camera images. Results and discussion: Dosimetric variations of 131I produced by using rhTSH in the remnant thyroid (groups II and III) were observed, absorbed doses were minor for groups treated with rhTSH. Conclusion: The application of the high activities > 5,500 MBq administered together with the application of rhTSH is safe in dosimetric terms, also for 9250 MBq do not exceed established limits of absorbed dose in the bone marrow. Furthermore, these high activities provide more than three times the radiation dose to remaining thyroid tissue and approximately 1.5 times to metastases. [ABSTRACT FROM AUTHOR]

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: Atotal of266DTCpatientswhoreceivedRAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected usingmachine learning randomforestmethod, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimalmodelwas validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that basedonempiricaladministration (Rate 1 (first rate):52.09%(137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, themodel significantly shortens thetime (days) toachieve targetTSHlevel (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Patients who receive systematic care typically have a better prognosis. RAI treatment plays a key role in eradicating any remaining thyroid lesions in DTC patients, hence decreasing the risk of distant metastases and cancer recurrence. As research continues to advance, RAI treatment is becoming more and more individualized. Because of the excellent prognosis for DTC patients, there is a relatively broad window for RAI treatment, making it easy to overlook when to receive RAI treatment. However, research on this issue can help patients with varying recurrence risk stratification make better decisions about when to begin RAI treatment following surgery, and physicians can schedule patients based on the severity of their disease. This will improve patient prognosis and lessen needless anxiety in addition to helping solve the problems of unjust healthcare resource distribution. In this review, we will mainly discuss the target population of RAI treatment as well as studies that examine the impact of RAI treatment timing on patient outcomes. In an effort to discourage DTC patients and physicians from selecting RAI therapy at random, we also review the possible negative effects of this treatment. [ABSTRACT FROM AUTHOR]

Aim: Differentiated thyroid cancer (DTC) is a common type of cancer that originates in the thyroid gland. This study aimed to predict the recurrence of differentiated thyroid carcinoma, in patient with well-DTC, using explainable machine learning (XAI) models. Material and Method: The study utilized a dataset from the UCI Machine Learning Repository, which included 383 patients and 13 candidate predictors. After a variable selection process using distance correlation, only four predictors (Response, Risk, T, and N) were retained for model building. Two XAI models, Fast Interpretable Greedy-Tree Sums (FIGS) and Explainable Boosting Machines (EBM), were employed. Results: The EBM model slightly outperformed the FIGS model in terms of accuracy. The study found that the most influential predictors of Well-DTC recurrence were the response to DTC treatment, risk status according to the American Thyroid Association classification, tumor size (T), and lymph node metastasis (N). Conclusion: In conclusion, this study successfully identified key risk factors for DTC recurrence using XAI models, providing interpretable insights for clinical decision-making and potential for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a rising incidence worldwide. Accurate prognostic models are essential for effective patient management. This study evaluates the prognostic value of various lymph node staging systems in DTC using a competing risks model. We used SEER database records (1998–2016) of 16,527 DTC patients, analyzing N stage, positive lymph node numbers (PLNNs), metastatic lymph node ratio (MLNR), log odds of positive lymph nodes (LODDS), and log odds of the negative lymph node (NLN)/T stage ratio (LONT). Univariate and multivariate analyses in a competing risks model were performed, along with subgroup analyses based on demographic and clinical characteristics. In this study of 16,527 patients with DTC, different lymph node staging systems showed different prognostic correlations in univariate and multivariate analyses. In particular, PLNNs showed significant prognostic correlations in several subgroups. Additionally, PLNNs were more suitable as a lymph node staging system for DTC than LODDS and MLNR in N1 stage subgroups, with an optimal cut-off of 13. Receiver operating characteristic curves, calibration curves and nomograms improved the clinical utility of the prognostic model based on PLNNs. Using competing risks model and subgroup analyses, we found that PLNNs had the best prognostic discriminatory efficacy for patients with DTC, especially those with N1 stage disease, and had an optimal cut-off value of 13. [ABSTRACT FROM AUTHOR]

Introduction: Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131). Areas covered: Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023. Expert opinion: In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs. [ABSTRACT FROM AUTHOR]

The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib, and 118 patients received a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55–1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo, though the difference in OS was not statistically significant. [ABSTRACT FROM AUTHOR]

Purpose: This two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT). Materials and Methods: All caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients' disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients' ultimate disease outcomes. Results: A total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p<0.001). The ROC curve showed that ps-Tg =20 ng/mL was the most accurate for predicting IR at the last follow-up. According to multivariate analysis, only ps-Tg, T stage and the therapeutic response to initial RAIT were significantly associated with IR. Conclusion: In caDTC patients, the ps-Tg level, T stage, and response to initial RAIT are critical final outcome indicators. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. Methods: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011–November 2023). Results: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). Conclusion: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the impact of tumor size on T3b differentiated thyroid cancer prognosis. No significant difference was found in the prognosis of small T3b tumors compared to the T1 tumors. Disease-specific survival, disease-free survival, and overall survival were significantly lower only in large T3b tumors compared to T2 and T3a. If T3b tumors are 2 cm or smaller, downstaging may be considered. The modified T category, reclassifying T3b (≤2 cm) as T1, showed better staging performance than the existing category. Adopting this modified T category could improve the prognostic accuracy of the AJCC/TNM staging. The prognostic significance of tumor size in T3b differentiated thyroid cancer (DTC) remains debated and underexplored. This study aimed to examine the varying impact of T3b based on tumor size, analyzing disease-specific survival, disease-free survival, and overall survival. A retrospective review of 6282 DTC patients who underwent thyroid surgery at Seoul St. Mary's Hospital from September 2000 to December 2017 was conducted. T3b was classified into three subcategories, T3b-1 (≤2 cm), T3b-2 (2–4 cm), and T3b-3 (>4 cm), using the same size criteria for T1, T2, and T3a. T3b-1 showed no significant difference in disease specific survival compared to T1, and both disease-free and disease-specific survival curves were sequentially ranked as T1, T3b-1, T2, T3a, T3b-2, and T3b-3. The modified T category, reclassifying T3b-1 as T1, demonstrated superior staging performance compared to the classic T category (c-index: 0.8961 vs. 0.8959 and AUC: 0.8573 vs. 0.8518). Tumors measuring 2 cm or less within the T3b category may require downstaging, and a modified T category could improve the precision of prognostic staging compared to the current T category. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used and has demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials on tyrosine kinase inhibitors (TKI) treatment have shown an improvement in overall and progression‐free survival in patients with advanced differentiated thyroid cancer. However, it is necessary to evaluate these studies to assess methodological biases and inconsistencies that may impact the effects. Objective: To map and assess the methodological quality of randomized clinical trials (RCTs) regarding randomization, allocation concealment, blinding, and selective reporting bias. Methods: RCTs assessing the efficacy and safety of TKI for the treatment of advanced differentiated thyroid cancer were included. The search was performed in the MEDLINE database. The included RCTs were assessed for the adequacy of the methodological steps, as recommended by the Cochrane Risk of Bias tool. Results: Nine studies were analyzed, of which 77.7% were classified as low risk of bias regarding selective reporting and 33.3% as high risk of reporting bias. The mean time between protocol registration and study publication was approximately 5.11 years. Moreover, 66.7% were classified as low risk of bias for randomization and allocation concealment, and 33.3% did not specify the randomization process and allocation concealment in a way that would allow the identification of occurrences of bias. Concerning blinding of participants and outcome assessors, 77.8% of the RCTs reported adequate blinding and were classified as having a low risk of bias, 11.1% had a high risk of bias, and 11.1% had insufficient information and were classified as having unclear risk of bias. Regarding the blinding of the outcome assessors, 33.3% did the blinding correctly, 11.1% did not blind, and 55.6% did not provide enough information. Conclusion: Overall, the assessed RCTs were predominantly at low risk of bias. The critical evaluation of these studies is essential to have confidence in the treatment estimated effect that will support clinical decision‐making and provide information to preclude future clinical study flaws. [ABSTRACT FROM AUTHOR]

Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues). [ABSTRACT FROM AUTHOR]