Comparing therapeutic outcomes: radioactive iodine therapy versus non-radioactive iodine therapy in differentiated thyroid cancer.

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 α 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.

Influencing Factors of Urinary Iodine Concentration Before and After Radioiodine Therapy for Differentiated Thyroid Cancer: An Initial Exploration of the Relationship With Therapeutic Efficacy.

OBJECTIVE: To investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors. METHODS: A total of 213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin (Tg), and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy was evaluated 6 months post-therapy. Statistical tests were used for data comparison, and logistic regression analysis for response factors. RESULTS: Post-therapy UIC and pre-post UIC difference were significantly correlated with Tg levels but not with reaching excellent response (ER) indicated by suppression of Tg levels below 0.2 ug/L. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for the low-intermediate and high-risk groups classified by primary tumor size, invasion, metastasis, and pathological type. CONCLUSION: Post-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

ObjectiveTo investigate the impact of urinary iodine concentration (UIC) and post-stimulatory thyroglobulin (ps-Tg) levels on the therapeutic efficacy of differentiated thyroid cancer (DTC) patients after initial radioiodine therapy, and to analyze the validity of these indicators as prognostic factors.Methods213 DTC patients received initial radioiodine therapy from June 2022 to September 2023. Demographic data and UIC were collected before and after therapy. Thyrotropin, thyroglobulin, and thyroglobulin antibody levels were assessed. Iodine uptake rate was measured, and therapeutic efficacy evaluated 6 months post-therapy. Statistical tests were used for data comparison and logistic regression analysis for response factors.ResultsPost-therapy UIC and pre-post UIC difference were significantly correlated with thyroglobulin levels but not with reaching excellent response (ER) where suppression of Tg levels below 0.2ug/l. Ps-Tg levels related to therapeutic efficacy, while UIC did not correlate with outcomes. ROC curve analysis found optimal ps-Tg cut-off points for low-intermediate and high-risk groupsclassified by primary tumor size, invasion, metastasis, and pathological type.ConclusionPost-treatment UIC and pre-post UIC difference correlate with ps-Tg levels. Ps-Tg levels are an associated factor for DTC, but UIC changes, despite correlation with ps-Tg, are not significantly related to outcomes and cannot be used as a prognostic factor.

TSH Stimulation before PET/CT as Our Frenemy in Detecting Thyroid Cancer Metastases-Final Results of a Retrospective Analysis.

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.

[68Ga]Ga-LNC1007 versus 2-[18F]FDG in the evaluation of patients with metastatic differentiated thyroid cancer: a head-to-head comparative study.

PURPOSE: This head-to-head comparison study aimed to compare the performance of [68Ga]Ga-FAPI-RGD (LNC1007) and 2-[18F]FDG PET/CT in the evaluation of patients with metastatic differentiated thyroid cancer (mDTC). METHODS: Ten unexplained hyperthyroglobulinemia (UHTg) patients and 20 patients with definite metastatic lesions of thyroid cancer (DmDTC) were enrolled in the study. All patients underwent both [68Ga]Ga-LNC1007 and 2-[18F]FDG PET/CT within 1 week. The final diagnosis was based on histopathological results and a comprehensive evaluation of laboratory tests and multimodal imaging characteristics. RESULTS: In patients with UHTg, [68Ga]Ga-LNC1007 PET/CT detected more metastatic lymph nodes (LNs) (17 vs. 15, P = 0.317) and lung lesions (2 vs. 0) than 2-[18F]FDG. In patients with DmDTC, [68Ga]Ga-LNC1007 PET/CT also detected more true positive lesions than 2-[18F]FDG (Total: 133 vs. 103, LN: 20 vs. 15, lung: 18 vs. 10, bone: 87 vs.73). [68Ga]Ga-LNC1007 PET/CT demonstrated significantly higher SUVmax (Total: 6.30 vs. 3.84, LN: 8.28 vs. 4.82, Lung: 3.31 vs. 1.49, Bone: 5.73 vs. 3.87, all P < 0.05) and TBR (Total: 6.92 vs. 4.93, LN: 6.48 vs. 4.16, Lung: 5.16 vs. 2.57, Bone: 7.22 vs. 5.41, all P < 0.05) in true positive lesions compared to 2-[18F]FDG. Specifically, the sensitivity of [68Ga]Ga-LNC1007 PET/CT was higher than that of 2-[18F]FDG in detecting lung and bone metastases (94.7% vs. 52.6% and 100% vs. 83.9%, all P < 0.05). [68Ga]Ga-LNC1007 PET/CT exhibited better specificity and accuracy in diagnosing LNs (96.9% vs. 66.7% and 96.3% vs. 68.5%, all P < 0.05). However, the specificity of [68Ga]Ga-LNC1007 for bone metastasis was inferior to 2-[18F]FDG (15.4% vs. 88.5%, P < 0.05). CONCLUSION: Compared with 2-[18F]FDG, [68Ga]Ga-LNC1007 PET/CT could detect more metastatic lesions, with higher SUVmax and TBR, in patients with mDTC. [68Ga]Ga-LNC1007 had better accuracy in the diagnosis of LN and lung metastasis. Trial registration ClinicalTrials.gov NCT05515783. Registered 01 May 2022. URL of registry https://classic. CLINICALTRIALS: gov/ct2/show/NCT05515783.

TERT promoter mutations contribute to adverse clinical outcomes and poor prognosis in radioiodine refractory differentiated thyroid cancer.

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.

Therapeutic efficacies of remnant ablation and radioiodine adjuvant therapy in differentiated thyroid cancer.

BACKGROUND: Successful ablation in 131I therapy for differentiated thyroid cancer (DTC) includes both remnant ablation (RA) and radioiodine adjuvant therapy (RAT). This study aimed to differentiate between the therapeutic efficacies of RA and RAT, investigate the factors associated with their effectiveness, and assess their impact on prognosis. METHODS: This retrospective study included patients with DTC who underwent initial 131I therapy at our tertiary center. The successful RA (SRA) and successful RAT (SRAT) was determined based on the 131I-diagnostic whole-body scan (Dx-WBS), TSH-stimulated thyroglobulin (sTg) levels, and neck ultrasound at the 6th month after 131I therapy. The patients were divided into complete response and persistent/recurrent disease groups during the follow-up period. RESULTS: A total of 232 patients were included, 91.8% (213/232) of patients achieved SRA, only 8.1% (19/232) failed RA (FRA). Among the 213 patients in the SRA group, 70.4% (150/213) achieved SRAT and 29.6% (63/213) failed RAT (FRAT). Only pre-ablation sTg >10 ng/mL (OR = 46.968, 95% CI 9.731-226.699, P < 0.001) was an independent risk factor predicting the failure of RAT. The prognostic analysis included 215 patients, and 6.1% (13/215) were classified as persistent/recurrent disease at the last follow-up. Both pre-ablation sTg >10 ng/mL (HR = 4.765, 95% CI 1.371-16.566, P = 0.014) and FRAT (HR = 10.104, 95% CI 1.071-95.304, P = 0.043) independently predicted persistent/recurrent disease. CONCLUSIONS: RA is easy to achieve successfully, whereas RAT evaluation provides greater value than RA for prognosis prediction. For patients with low Tg levels and no imaging evidence of disease, routine Dx-WBS during follow-up has minimal significance.

Effects of a mobile health intervention based on a multitheoretical model of health behavior change on anxiety and depression, fear of cancer progression, and quality of life in patients with differentiated thyroid cancer: A randomized controlled trial.

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 < .026), with no change in the control group, demonstrating a significant difference. The intervention group also had significantly lower anxiety (P < .015) and depression (P < .032) scores compared to controls. All PHQ-4 scores improved in the intervention group except for "Little interest or pleasure in doing things." Anxiety levels were significantly lower in the intervention group (P < .026) but remained unchanged in controls. The control group exhibited a significant increase in FCR-4 scores at follow-up, differing from the intervention group (P < 0.001). Quality of life scores did not differ at baseline but saw a significant improvement in the intervention group, while the control group experienced no significant change. The intervention group had higher VAS scores (P < .030) and greater health education satisfaction across all dimensions (P < .019). CONCLUSIONS: The MTM-based mHealth intervention significantly benefits DTC patients by reducing anxiety, fear of cancer recurrence, and improving quality of life, though its effect on depression requires further investigation. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2200064321.

Approach to the patient with thyroid nodules: considering GLP-1 receptor agonists.

Glucagon-like peptide 1 receptor agonists (GLP1RA) have rapidly changed the landscape of diabetes and obesity treatment. Enthusiasm for their use is tempered with concerns regarding their risk for inducing C-cell tumors based on preclinical studies in rodents. A black-box warning from the United States Food and Drug Administration (USFDA) recommends against using GLP1RA in patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2A or 2B (MEN2), providing clear guidance regarding this cohort of patients. However, emerging data also suggest an increased incidence of differentiated thyroid cancer (DTC) in patients treated with these agents. Other studies, though, have not confirmed an association between GLP1RA and DTC. With conflicting results concerning thyroid cancer risk, there is no clear consensus regarding the optimal approach to screening patients prior to initiating the medications and/or evaluating for thyroid cancer during GLP1RA treatment. Within the context of patient cases, this review will summarize the existing data, describe ongoing controversies, and outline future areas for research regarding thyroid cancer risk with GLP1RA use.

Management of follicular thyroid carcinoma.

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.

Pathologic Characteristics and Surgical Outcomes of Pediatric Versus Adult Well-Differentiated Thyroid Cancer.

OBJECTIVE: Despite the rising incidence of pediatric differentiated thyroid cancer (DTC), postoperative outcomes for such tumors have not been well-characterized. The objective of this study was to compare pathologic tumor characteristics and treatment outcomes for pediatric and adult patients with DTC. STUDY DESIGN: Retrospective case-control study. SETTING: National database. METHODS: Pediatric (<18 years old) and adult (≥18 years old) patients who underwent surgery for DTC in the National Cancer Database (2004-2020) were included. Multivariable logistic, negative binomial, and linear regressions were used to compare pathologic tumor characteristics, treatment characteristics, and short-term surgical outcomes. RESULTS: 337,864 patients with DTC met the study eligibility criteria; 3584 (1.1%) were pediatric patients and 334,280 (98.9%) were adults. After adjustment, pediatric patients were found to have higher rates of pathologic T upstaging (adjusted odds ratio [ORadj]: 1.40, 95% confidence interval [CI]: 1.23-1.59), N upstaging (ORadj: 2.53, 95% CI: 2.23-2.88), and extrathyroidal extension (ORadj: 1.58, 95% CI: 1.29-1.94), compared to adult patients. Pediatric patients were also more likely to receive neck dissection (ORadj: 2.80, 95% CI: 2.55-3.07) and radioactive iodine (ORadj: 1.42, 95% CI: 1.30-1.55). Pediatric patients had higher rates of positive surgical margins (ORadj: 1.25, 95% CI: 1.11-1.41) and 30-day readmissions (ORadj: 1.26, 95% CI: 1.00-1.58) than adult patients. CONCLUSION: These findings demonstrate that pediatric DTC is associated with more aggressive disease presentations, more radical treatment, and worse short-term surgical outcomes compared to DTC in adults. Pediatric DTC should be considered a unique clinical entity that requires personalized evaluation and multidisciplinary treatment by specialized providers.

Differentiated thyroid cancer and adverse pregnancy outcomes: a propensity score-matched retrospective cohort study.

Background: Differentiated 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. Methods: We 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. Results: After 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)]. Conclusions: DTC 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.

Mental Health and Quality of Life of Patients with Differentiated Thyroid Cancer Pre and Post Radioactive Iodine Treatment: A Prospective Study.

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.

Analysis of the ideal cutoff age as a predictor of differentiated thyroid cancer using the Surveillance, Epidemiology, and End Results database.

Background: It has been discovered that the prognosis of patients with differentiated thyroid cancer (DTC) correlates with age at initial diagnosis. However, there are disagreements over the optimal cutoff age among the numerous staging and risk stratification criteria, which make it inconsistent to predict the clinical prognosis of specific DTC patients. This study aimed to determine the optimum cutoff age for diagnosis in relation to the clinical outcomes of DTC using data from the Surveillance, Epidemiology and End Results (SEER) database. Methods: The best age cutoff value was determined by the X-tile software. The link between clinical characteristics and cancer-specific survival (CSS) was examined using univariate and multivariate Cox regression models. An additional application of the independent prognostic criteria, such as age stratifications, was applied to construct a nomogram model for predicting the chances of patient survival. Results: The most accurate diagnosis cutoff age for DTC patients was suggested to be 67 years old. The multivariate analysis, using factors determined by univariate analysis, showed that age [>67 years, hazard rate (HR) =5.049, 95% confidence interval (CI): 4.509-5.653, P<0.001], sex (female, HR =0.651, 95% CI: 0.584-0.727, P<0.001), tumor size (>20 and ≤40 mm, HR =2.296, 95% CI: 1.983-2.658, P<0.001; >40 mm, HR =4.976, 95% CI: 4.304-5.752, P<0.001), lymphadenectomy (HR =1.337, 95% CI: 1.186-1.506, P<0.001), distant metastasis (HR =12.166, 95% CI: 10.749-13.769, P<0.001) and surgical treatment (HR =0.173, 95% CI: 0.144-0.210, P<0.001) were independent factors for CSS. Patients in the high-risk group had worse survival rates, and the C-index for the CSS prediction model with age (cutoff of 67) and other independent clinicopathological variables was 0.906. Conclusions: Accordingly, the optimal cutoff age for predicting death from DTC specifically is 67 years old at the time of the initial diagnosis. It might be a more suitable factor when used in risk stratification for patients with DTC.

Efficacy of color Doppler ultrasound signs combined with serum tumor-specific growth factor in the diagnosis of differentiated thyroid cancer.

OBJECTIVE: To construct a diagnostic model for follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma (PTC), both subtypes of differentiated thyroid carcinoma (DTC), using color Doppler ultrasound signs in conjunction with serum laboratory markers. METHODS: We conducted a retrospective analysis of patients with thyroid nodules who underwent ultrasonography at Yulin Hospital from February 2021 to March 2023. The cohort included 269 subjects: 105 with benign nodules and 164 with DTC (59 with FTC and 105 with PTC). We compared baseline demographics and laboratory indices between the groups. Diagnostic values of ultrasound features and laboratory markers were assessed using receiver operating characteristic (ROC) curves, and logistic regression was employed to pinpoint independent diagnostic factors for FTC. A predictive nomogram was subsequently developed based on these factors. RESULTS: There were significant differences between the benign and malignant groups regarding ultrasound signs (including border, morphology, echogenicity, calcification, blood flow, lymph node zoning) and laboratory indices (free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), vascular endothelial growth factor (VEGF), tumor-specific growth factor (TSGF)), with all P-values <0.05. The areas under the curve (AUCs) for FT3, FT4, Tg, TSH, VEGF, and TSGF were all above 0.75, with Tg achieving the highest at 0.91. Logistic regression identified borders, morphology, echogenicity, VEGF, and TSGF as independent diagnostic factors for distinguishing between FTC and PTC, with significant P-values. The constructed nomogram demonstrated an AUC of 0.853, indicating high diagnostic accuracy. Both calibration and decision curve analysis (DCA) validated the model's stability and clinical utility. CONCLUSION: We successfully developed a nomogram combining ultrasound features and serum markers that enhances the diagnostic precision for FTC. This model offers a valuable tool for clinical diagnostics in differentiated thyroid cancer.

Changes in Thyroglobulin Antibody Levels in Differentiated Thyroid Cancer Patients After Thyroidectomy: A Retrospective Study in Basrah, Iraq.

INTRODUCTION: Differentiated thyroid cancer (DTC), the most common endocrine malignancy is subdivided into papillary (the most common) and follicular type. Generally, DTC has a good prognosis with standard treatments such as surgery and, in some cases, radioactive iodine (RAI). Post-treatment follow-up includes thyroglobulin (Tg) and anti-thyroglobulin antibody (TgAb) measurement and imaging to assess treatment success and detect recurrence. However, TgAb can interfere with Tg measurements, making it essential to measure TgAb at different times (months).  Aim of the study: The aim of this study was to evaluate the changes in TgAb level in DTC patients after thyroidectomy and its association with recurrence. METHODS: This was a retrospective cohort study done at the Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC), Basrah, Iraq, for individuals diagnosed with DTC between 2008 and 2023. The data collected were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States). The categories were classified according to the TgAb level as: (i) elevated (>115 IU/ml) and (ii) normal (<115 IU/ml), where TgAb levels measured at 0-6 months, 6-12 months, 24-36 months, 36-48 months, and beyond 48 months. RESULTS: The mean age at diagnosis of the study population (n=108) was 40.15 years with a female-to-male ratio of 4:1. Among these individuals, 52.8% (n=57) were found to be obese. Total thyroidectomy was performed on 84.3% (n=91). Papillary thyroid cancer was diagnosed in 69.5% (n=75). TgAb levels were influenced by body mass index (BMI); higher BMI (>30kg/m2) was associated with less consistent TgAb normalization, particularly beyond 48 months (P = 0.04). The study found no significant differences in TgAb normalization based on gender, age, BMI, type of surgery, type of cancer, American Thyroid Association (ATA) risk of recurrence, or radioactive iodine (RAI) treatment. CONCLUSION:  Factors including gender, age, type of surgery, type of cancer, ATA risk of recurrence, and RAI treatment did not significantly affect TgAb normalization in DTC individuals over the study period. However, higher BMI is associated with less consistent TgAb normalization in the long term.

Efficacy and safety of targeted therapy for radioiodine-refractory differentiated thyroid cancer: a meta-analysis.

PURPOSE: To evaluate the efficacy and safety of current targeted drug therapies for radioiodine-refractory differentiated thyroid cancer (RR-DTC). METHODS: This was a meta-analysis of relevant randomized controlled trials (RCTs) and single-arm studies searched across PubMed, Embase, Cochranes, and Web of Sciences up to September 12, 2023. Stata15.0 software was used to assess overall survival (OS), progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and adverse effects (AEs). The Cochrane Bias Risk tool was used to assess literature quality and trial bias and RevMan 5.4 was used to generate a quality assessment map. RESULTS: A total of 8 RCTs and 17 single-arm studies with 3,270 patients on 7 drugs-vandetanib, sorafenib, lenvatinib, cabozantinib, apatinib, donafenib, and anlotinib-were included. Targeted therapy with these drugs effectively prolonged PFS and OS in patients with RR-DTC with overall HRs of 0.35 (95% CI 0.23-0.53, P < 0.00001) and 0.53 (95% CI 0.32-0.86, P < 0.00001), respectively. ORR and DCR were also prolonged, with overall RRs of 27.63 (95% CI 12.39-61.61, P<0.00001) and 1.66 (95% CI 1.48-1.86, P<0.00001), respectively. The subgroup analysis using Effect Size (ES) showed that apatinib had the best effect on ORR with an ES of 0.66 (95% CI 0.49-0.83, P<0.00001) and DCR with a ES of 0.95 (95% CI 0.91-1.00, P<0.00001). Common drug adverse effects included hypertension, diarrhea, proteinuria, and fatigue. CONCLUSION: The currently used targeted drug therapies for RR-DTC can significantly improve clinical outcomes and the new drug apatinib demonstrates promise for potentially superior performance.

Predicting excellent response to radioiodine in differentiated thyroid cancer using machine learning.

Objective: If excellent response (ER) occurs after radioactive iodine (RAI) treatment in patients with differentiated thyroid carcinoma (DTC), the recurrence rate is low. Our study aims to predict ER at 6-24 months after RAI by using machine learning (ML) methods in which clinicopathological parameters are included in patients with DTC without distant metastasis. Methods: Treatment response of 151 patients with DTC without distant metastasis and who received RAI treatment was determined (ER/nonER). Thyroidectomy ± neck dissection pathology data, laboratory, and imaging findings before and after RAI treatment were introduced to ML models. Results: After RAI treatment, 118 patients had ER and 33 had nonER. Before RAI treatment, TgAb was positive in 29% of patients with ER and 55% of patients with nonER (p = 0.007). Eight of the ML models predicted ER with high area under the ROC curve (AUC) values (> 0.700). The model with the highest AUC value was extreme gradient boosting (AUC = 0.871), the highest accuracy shown by gradient boosting (81%). Conclusions: ML models may be used to predict ER in patients with DTC without distant metastasis.

Impact of extrathyroidal autoimmune diseases on clinical features and the efficacy of Iodine-131 therapy in patients with differentiated thyroid cancer.

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.

A predictive model for L-T4 dose in postoperative DTC after RAI therapy and its clinical validation in two institutions.

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: A total of 266 DTC patients who received RAI 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 using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was 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 based on empirical administration (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, the model significantly shortens the time (days) to achieve target TSH level (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.

Vitamin D receptor polymorphisms associate with the efficacy and toxicity of radioiodine-131 therapy in patients with differentiated thyroid cancer.

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.