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Accurate postoperative assessment is critical for optimizing 131 I therapy in patients with papillary thyroid cancer (PTC). This study aimed to develop a pathology model utilizing postoperative digital pathology slides to predict lymph node and/or distant metastases on post-therapeutic 131 I scan after initial 131 I treatment in PTC patients. A retrospective analysis was conducted on 229 PTC patients who underwent total or near-total thyroidectomy and subsequent 131 I treatment after levothyroxine (LT4) withdrawal between January 2022 and August 2023. The pathology model was developed through two stages: patch-level prediction and WSI-level prediction. The clinical model was constructed using statistically significant variables identified from univariate and multivariate logistic regression analysis. Of the 229 patients, 19.6% (45/229) exhibited 131 I-avid metastatic foci in post-therapeutic 131 I scan. Multifactorial analysis identified stimulated thyroglobulin (sTg) as the sole independent risk factor. The AUC of the pathology model in the training and test cohorts were 0.976 (95% CI 0.948-1.000) and 0.805 (95% CI 0.660-0.951), respectively, which were significantly higher than the clinical model (AUC 0.652 and 0.548, Pall < 0.05). This model has the potential to serve as a valuable tool for clinicians in tailoring treatment strategies, thereby optimizing therapeutic outcomes for PTC patients., (© 2024. The Author(s).)

Radioiodine (RAI) therapy after surgery, is an important component for the treatment of patients with papillary thyroid cancer (PTC), the most common thyroid cancer. In this study we sought to evaluate the cancer-specific survival (CSS) impact of RAI in specific thyroid cancer subgroups. The Surveillance, Epidemiology, and End Results (SEER) database were used to identify patients with PTC who underwent surgery between 2000 and 2019. Patients not treated with RAI were compared to those treated with RAI using propensity score matching (PSM) on the basis of identical inclusion criteria. A total of 106 333 patients were identified from the SEER database. RAI therapy was associated with improved CSS in the matched cohort (HR: 0.83; 95% CI: 0.72-0.96, p=0.01) but not in the unmatched data set (HR: 1.46; 95% CI: 1.30-1.64, p<0.001) among all PTC patients regardless of disease stage. Detailed analyses, however, showed that only patients with high-risk disease (pT3N1, pT4N1) experienced the greatest benefit in CSS. In the lower disease stages, no significant differences were recognized in the group of PTC patients with or without RAI therapy. One exception: in the group of PTC patients in stage pT1bN0, a significant difference was seen towards RAI. This is, however, most likely due to the large number of patients investigated. In summary, RAI therapy should not be used in low-risk PTC patients and might be used to some extent in intermediate-risk PTC patients. The histological suptype of the tumor needs to be considered in this context., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Papillary thyroid cancer (PTC) is the most common thyroid malignancy, characterized by its slow progression and favorable prognosis. This study re-evaluates the efficacy of radioactive iodine (RAI) therapy versus no RAI in low-risk PTC patients following total thyroidectomy., Methods: A retrospective analysis was conducted on 588 patients treated between 2010 and 2016 at a major tertiary center in Turkey. Patients were divided into two cohorts: those receiving total thyroidectomy (TT) with high-dose RAI (100 mCi) and those receiving TT alone. A matched cohort of 138 patients per group was analyzed to minimize bias., Results: Follow-up data indicated that at 24 months, the RAI group demonstrated a higher percentage of excellent treatment responses (86%) compared to the non-RAI group (74%). Long-term follow-up showed that 99.3% of the RAI group achieved no evidence of disease (NED), versus 90.6% in the non-RAI group. Recurrence rates were significantly lower in the RAI group (1%) compared to the non-RAI group (5.8% with a > 2.0 ng/ml cut-off for biological events)., Conclusion: In summary, the findings from this study underscore the efficacy of RAI therapy in reducing recurrence rates and enhancing long-term disease control in low-risk papillary thyroid cancer patients. While total thyroidectomy alone is effective, the addition of RAI therapy provides a marked improvement in treatment responses and reduces the risk of disease recurrence. This indicates that personalized treatment plans incorporating RAI may offer significant advantages in managing low-risk PTC., (© 2024. The Author(s).)

This study explored the role of radioiodine therapy (RAI) in low-risk thyroid cancer patients and examined the disease-specific survival (DSS) rates in a large cohort of differentiated thyroid cancer patients (DTC). We obtained patient data from SEER database. Patients who underwent total thyroidectomy were included and categorized into three groups based on histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). Patients with distant metastasis, tumor size ≥ 200 mm, chemotherapy, or any type of radiation other than RAI were also excluded. A nomogram was developed and tested for discrimination and calibration. In total, 96,532 thyroid cancer cases were examined, including 59,460 C-PTC, 31,583 FV-PTC, and 5,489 FTC cases. Age > 65 years and male sex were correlated with lower survival rates across the subtypes. In addition, extrathyroidal extension had a worse survival effect in patients with FTC. DSS rates were compared between patients who received RAI and those who did not, with a 3% difference in C-PTC (94% vs. 91%, p < 0.001), 2% in FV-PTC (92% vs. 90%, p < 0.001), and 1% in FTC (89% vs. 88%, p = 0.084) at 15 years. The nomograms for long-term DSS showed high discriminatory abilities with C-indices of 0.815, 0.805, and 0.781 for C-PTC, FV-PTC, and FTC, respectively. The developed nomogram can be used in the treatment plan for patients with DTC. Our study emphasizes the prognostic factors for DTC and highlights the need for personalized treatment plans based on individual risk profiles., (© 2024. The Author(s).)

High-activity radioactive iodine (RAI) therapy for metastatic thyroid cancer (TC) requires isolation to minimize radiation exposure to third parties, thus posing challenges for patients needing hands-on care. There are limited data on the approach to high-activity RAI treatment in paraplegic patients. We report a state-of-the-art multidisciplinary approach to the management of bedbound patients, covering necessary radiation safety measures that lead to radiation exposure levels as low as reasonably achievable. Given the limited literature resources on standardized approaches, we provide a practical example of the safe and successful treatment of a woman with BRAFV600E -mutant tall-cell-variant papillary TC and pulmonary metastases, who underwent dabrafenib redifferentiation before RAI therapy. The patient was 69 y old and had become paraplegic because of a motor-vehicle accident. Since caring for a paraplegic patient with neurogenic bowel and bladder dysfunction poses radiation safety challenges, a multidisciplinary team comprising endocrinologists, nuclear medicine physicians, radiation safety specialists, and the nursing department developed a radiation mitigation strategy to ensure patient and staff safety during RAI therapy. The proposed standardized approach includes thorough monitoring of radiation levels in the workplace, providing additional protective equipment for workers who handle radioactive materials or are in direct patient contact, and implementing strict guidelines for safely disposing of radioactive waste such as urine collected in lead-lined containers. This approach requires enhanced training, role preparation, and practice; use of physical therapy equipment to increase the exposure distance; and estimation of the safe exposure time for caregivers based on dosimetry. The effective and safe treatment of metastatic TC in paraplegic patients can be successfully implemented with a comprehensive radiation mitigation strategy and thorough surveying of personnel for contamination., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: It remains unclear whether the time interval between total thyroidectomy and radioactive iodine (RAI) therapy influences clinical outcomes in papillary thyroid carcinoma (PTC). This study aims to evaluate the impact of the timing to initiate RAI therapy on the response in PTC patients., Methods: We retrospectively included 405 patients who underwent total thyroidectomy and subsequent RAI therapy at two tertiary hospitals in southwest China. Patients were categorized into two groups based on the interval between thyroidectomy and initial RAI therapy, that is, an early group (interval ≤90 days, n  = 317) and a delayed group (interval >90 days, n  = 88). Responses to RAI therapy were classified as excellent, indeterminate, biochemical incomplete, or structural incomplete. Univariate and multivariate analyses were conducted to identify factors associated with a nonexcellent response., Results: Excellent responses were observed in 77.3% of the early group and 83.0% of the delayed group ( P  = 0.252). No significant impact of RAI therapy timing was also observed across all American Thyroid Association risk classification categories. These findings persisted when patients were analyzed separately according to RAI dose (intermediate-dose group: 3.7 GBq [ n  = 332]; high-activity group: ≥5.5 GBq [ n  = 73]), further subdivided by the timing of RAI therapy. Multivariate analysis identified lymph node dissection, RAI dose, and stimulated thyroglobulin as independent risk factors for excellent response ( P  < 0.05)., Conclusion: The timing of initial RAI therapy following surgery did not significantly affect outcomes in patients with PTC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Differentiated thyroid cancer (DTC) presents a complex clinical challenge, especially in patients with distant metastases and resistance to standard treatments. This study aimed to investigate the influence of specific genes and their germline single nucleotide polymorphisms (SNPs) linked to both inflammatory processes and other neoplasms on the clinical and pathological characteristics of DTC, particularly their potential impact on radioiodine (RAI) treatment efficacy., Methods: This retrospective analysis involved a cohort of 646 patients diagnosed with DTC after thyroidectomy. Study covering 1998-2014, updated in 2023, included 567 women and 79 men (median age: 49; range: 7-83). SNP selection targeted functional significance, while mutational status was assessed by pyrosequencing for comprehensive characterization. Patient genetic profiles were assessed for associations with disease characteristics, RAI response, and cancer pathology., Results: Significant correlations emerged between certain SNPs and DTC features. Notably, the NOD2 c.802 T > C variant (rs2066842) was identified as a marker distinguishing between papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Moreover, the c.802 T allele was associated with an enhanced response to RAI treatment, indicating a more substantial decrease in posttreatment stimulated thyroglobulin (sTg) concentrations. The NFKB1A allele c.126A (rs696) exhibited connections with lower FTC stages and a reduced probability of multifocality., Conclusion: This study explored the molecular mechanisms of particular SNPs, highlighting the role of NOD2 in innate immunity and the stress response, and its potential impact on RAI efficacy. This research underscores the clinical promise of SNP analysis and contributes to personalized treatment strategies for DTC, emphasizing the relevance of genetic factors in cancer progression and treatment outcomes., (© 2024. The Author(s).)

Abstract: A 75-year-old woman with papillary thyroid carcinoma who underwent 131 I radioiodine treatment was incidentally found to have an established left cerebral infarct demonstrating 131 I uptake on posttherapy whole-body scan. False-positive iodine accumulation can occur in benign processes and other malignancies, necessitating awareness among nuclear medicine physicians to avoid misdiagnosing metastatic disease. SPECT/CT can be utilized to enhance diagnostic accuracy when needed., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Lymph node metastasis is the major cause of increased recurrence and death in patients with papillary thyroid carcinoma (PTC). We evaluate the clinicopathologic factors affecting excellent response (ER) in patients with PTC with lymph node metastasis following operation and 131 I ablation therapy., Methods: A total of 423 patients with PTC with lymph node metastasis who underwent thyroidectomy and postoperative 131 I ablation therapy were enrolled. The relationship between clinicopathological factors affecting ER achievement was analyzed., Results: Multivariate analysis showed that the foci diameter (≤1 cm), unifocal, combination with Hashimoto's thyroiditis (HT), lymph node metastases rate (LR) (≤40%), no postoperative lymph node metastasis, low preablative stimulated thyroglobulin (ps-Tg) level (≤3.87 ng/mL), and the time of 131 I ablation therapy (one time) were positively correlated with the ER achievement [odds ratio (OR): 1.744, 3.114, 3.920, 4.018, 2.074, 9.767, and 49.491, respectively; all p < 0.05]. The receiver operating characteristic (ROC) curves showed that the cutoff values of ps-Tg and LR were 4.625 ng/mL and 50.50%, respectively. The AUC of ROC of ps-Tg and LR for predicting ER achievement was 0.821 and 0.746, respectively. The Tg and the cumulative risk of non-ER elevated with the increase of LR, especially for the high-level ps-Tg (>4.625 ng/mL) group., Conclusion: The foci diameter and number, combination with HT, LR, and ps-Tg level are independent factors for ER. Ps-Tg level and LR are valid predictive factors for the efficacy of 131 I therapy in patients with PTC. The predictive value of the cumulative risk of non-ER can be improved by the combination of ps-Tg and LR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Li, Yu, Wang, Guo, Ni, Zhao, Wang and Dong.)

Background: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored., Methods: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans., Results: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001., Conclusion: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy., (© 2024. The Author(s).)

Purpose: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients., Methods: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre., Results: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively)., Conclusions: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Our main aim was to explore whether cognitive behavior therapy based on the health education pathway (CBT-HEP) can effectively alleviate the distress, anxiety, and depression of papillary thyroid carcinoma (PTC) patients after 131 I treatment. In addition, we investigated the critical factors that can significantly affect the distress and quality of life in PTC patients before 131 I treatment., Methods: In total, 496 people were screened and 357 were enrolled, followed by randomization of those with a distress thermometer (DT) ≥4. Patients in the experimental group received CBT-HEP intervention, and patients in the control group were given casual conversation., Results: The scores of DT, Hamilton Anxiety Scale (HAMA) and Patient Health Questionnaire-9 (PHQ-9) in CBT-HEP group decreased gradually after intervention. In control group, DT scores decreased significantly, while HAMA and PHQ-9 scores did not change significantly., Conclusion: CBT-HEP is effective in relieving distress, anxiety and depression in PTC patients. In addition, female sex, lifestyle, hypothyroidism, negative emotions, related symptoms, fear of tumor recurrence and radiation safety are the critical factors affecting mental health and quality of life., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in papillary thyroid carcinoma (PTC)., Methods: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors., Results: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4-23.6%), these individuals had larger tumors (median 19 mm vs. 12 mm, P<0.001) with more frequent extraglandular invasion (54.0% vs. 17.1%, P<0.001), regional lymph nodes involvement (29.8% vs. 12.6%, P=0.003)and distant metastasis (10.9% vs. 1.9%, P=0.003) at diagnosis. VI was an independent predictor for regional lymph node and/or distant metastasis at diagnosis (OR 2.93 [IC 95% 1.16-7.41, P=0.008]). After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence., Conclusions: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.

To explore the feasibility of combined radiomics of post-treatment I-131 total body scan (TBS) and clinical parameter to predict successful ablation in low-risk papillary thyroid carcinoma (PTC) patients. Data of low-risk PTC patients who underwent total/near total thyroidectomy and I-131 ablation 30 mCi between April 2015 and July 2021 were retrospectively reviewed. The clinical factors studied included age, sex, and pre-ablative serum thyroglobulin (Tg). Radiomic features were extracted via PyRadiomics, and radiomic feature selection was performed. The predictive performance for successful ablation of the clinical parameter, radiomic, and combined models (radiomics combined with clinical parameter) was calculated using the area under the receiver operating characteristic curve (AUC). One hundred and thirty patients were included. Successful ablation was achieved in 77 patients (59.2%). The mean pre-ablative Tg in the unsuccessful group (15.50 ± 18.04 ng/ml) was statistically significantly higher than those in the successful ablation group (7.12 ± 7.15 ng/ml). The clinical parameter, radiomic, and combined models produced AUCs of 0.66, 0.77, and 0.87 in the training sets, and 0.65, 0.69, and 0.78 in the validation sets, respectively. The combined model produced a significantly higher AUC than that of the clinical parameter (p < 0.05). Radiomic analysis of the post-treatment TBS combined with pre-ablative serum Tg showed a significant improvement in the predictive performance of successful ablation in low-risk PTC patients compared to the use of clinical parameter alone.Thai Clinical Trials Registry TCTR identification number is TCTR20230816004 ( https://www.thaiclinicaltrials.org/show/TCTR20230816004 )., (© 2024. The Author(s).)

Context: Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial., Objective: This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database., Methods: We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS., Results: After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results., Conclusion: RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The utility of radioiodine (RAI) therapy in intermediate-risk papillary thyroid carcinoma (PTC) remains a topic of ongoing discussion. This systematic review and meta-analysis aimed to consolidate existing evidence on the impact of postoperative RAI therapy on recurrence and survival outcomes in intermediate-risk PTC., Methods: A literature search was performed using relevant keywords in PubMed, Scopus, and EMBASE. Articles from January 2008 to March 2023 were included. Odds ratios (ORs) and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis., Results: Eleven articles comprising 56,266 intermediate-risk PTC patients were included. 41,530 (73.8%) patients underwent postoperative RAI therapy, while 14,736 (26.2%) patients were kept on no-RAI (NOI) follow-up. No significant reduction in rates of structural disease recurrence was noted with RAI therapy in comparison to NOI follow-up (pooled univariate OR, 0.73, 95% confidence interval [CI], 0.29-1.87, I 2  = 75%). RAI therapy was not a significant predictor of better recurrence-free survival (pooled multivariate HR, 0.21; 95% CI, 0.01-3.74, I 2  = 94%). Interestingly, RAI therapy was associated with an overall survival benefit compared to NOI follow-up (pooled multivariate HR, 0.63; 95% CI, 0.48-0.82, I 2  = 79%)., Conclusions: This meta-analysis did not establish a conclusive benefit of RAI therapy in preventing structural disease recurrence or improving recurrence-free survival in intermediate-risk PTC. However, these results need to be interpreted with caution owing to significant heterogeneity in the existing literature. A prospective, randomised clinical trial is the need of the hour to better understand the effect of RAI therapy on long-term outcomes., (© 2023 John Wiley & Sons Ltd.)

The curative treatment options for papillary thyroid cancer (PTC) encompass surgical intervention, radioactive iodine administration, and chemotherapy. However, the challenges of radioiodine (RAI) resistance, metastasis, and chemotherapy resistance remain inadequately addressed. The objective of this study was to investigate the protective role of hypoxia-inducible factor-1α (HIF-1α) in 131 I-resistant cells and a xenograft model under hypoxic conditions, as well as to explore potential mechanisms. The effects of HIF-1α on 131 I-resistant BCPAP and TPC-1 cells, as well as the xenograft model, were assessed in this study. Cell viability, migration, invasion, and apoptosis rates were measured using Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays. Additionally, the expressions of Ki67, matrix metalloproteinase-9 (MMP-9), and pyruvate kinase M2 (PKM2) were examined using immunofluorescence or immunohistochemistry assays. Sodium iodide symporter and PKM2/NF-κBp65 relative protein levels were detected by western blot analysis. The findings of our study indicate that siHIF-1α effectively inhibits cell proliferation, cell migration, and invasion in 131 I-resistant cells under hypoxic conditions. Additionally, the treatment of siHIF-1α leads to alterations in the relative protein levels of Ki67, MMP-9, PKM2, and PKM2/NF-κBp65, both in vivo and in vitro. Notably, the effects of siHIF-1α are modified when DASA-58, an activator of PKM2, is administered. These results collectively demonstrate that siHIF-1α reduces cell viability in PTC cells and rat models, while also mediating the nuclear factor-κB (NF-κB)/PKM2 signaling pathway. Our findings provide a new rationale for further academic and clinical research on RAI-resistant PTC., (© 2023 Wiley Periodicals LLC.)

Introduction: The radioiodine-refractory (RAI-R) recurrent papillary thyroid carcinomas (PTCs) are more frequent in elderly patients and have an unfavorable prognosis. Data on the prevalence and characteristics of RAI-R recurrent PTCs in patients of young and middle age with or without a history of radiation exposure in childhood are poorly described. The aim of the current study was: i) to determine the frequency of RAI-R recurrent PTCs among donors of the Chornobyl Tissue Bank (CTB) and analyze the clinicopathological features of primary tumors (PTs), primary metastases (PMTSs), recurrent metastases (RMTSs) and risk factors for RMTS, and ii) to determine the immune checkpoint status (ICS) of the RAI-R recurrent PTCs and to assess the factors associated with ICS positivity., Methods: Sixty RAI-R recurrent PTCs (46 exposed to radiation and 14 non-exposed, 2.5% of all cases registered with the CTB) from the Ukrainian patients aged up to 48 years were identified., Results: The clinicopathological characteristics of the PTs moderately to weakly resembled those of the PMTS and RMTS from the same patients while the metastatic tissues were highly similar. The multivariate model of RMTS included the dominant solid-trabecular growth pattern of the PT, cystic changes, N1b metastases, and the probability of a causation (POC) of PTC by radiation as risk factors. Among these factors, the lateral PMTS (N1b) had the strongest effect. The longer period of latency (a POC component) was the second statistically significant characteristic. ICS percent agreement between the PT and RAI-R RMTS was 91.5%; 23.7% of PTs and 28.8% of RMTSs had positive ICS (positive PD-L1 tumor epithelial cells (TECs) and positive PD-L1/PD1 tumor-associated immune cells). ICS positivity of PTs was associated with pronounced oncocytic changes and high density of the p16 INK4A -positive TECs in the invasive areas of PTs. In RMTSs, ICS positivity was associated with pronounced oncocytic changes and Ki-67 labeling index ≥ 4.5% of PTs, and the dominant solid-trabecular growth pattern, Ki-67 labeling index ≥ 7.6% and p16 INK4A -positivity of RMTS., Discussion: The findings are of clinical relevance and may be useful for developing individual treatment approaches for patients with RAI-R recurrent PTCs possibly involving immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bogdanova, Rogounovitch, Zurnadzhy, Mitsutake, Tronko, Ito, Bolgov, Chernyshov, Gulevatyi, Masiuk, Yamashita and Saenko.)

Background: We aimed to evaluate the impact of radioactive iodine on disease-specific survival in intrathyroidal (N0M0) papillary thyroid carcinoma >4 cm, given conflicting data in the American Thyroid Association guidelines regarding their management., Methods: The Surveillance, Epidemiology, and End Results database was queried for N0M0 classic papillary thyroid carcinoma >4 cm. Kaplan-Meier estimates were performed to compare disease-specific survival between radioactive iodine-treated and untreated groups. A multivariable Cox regression was performed to identify predictors of disease-specific survival., Results: There were more patients aged ≥55 (41.7% vs 32.3%, P = .001) and fewer multifocal tumors (25.3% vs 30.6%, P = .006) in the no radioactive iodine group. Ten-year disease-specific survival was similar between the radioactive iodine treated and untreated groups (97.2% vs 95.6%, P = .34). Radioactive iodine was not associated with a significant disease-specific survival benefit (adjusted hazard ratio = 0.78, confidence interval [0.39-1.58], P = .49). Age ≥55 (adjusted hazard ratio = 3.50, confidence interval [1.69-7.26], P = .001) and larger tumor size (adjusted hazard ratio = 1.04, confidence interval [1.02-1.06], P < .001) were associated with an increased risk of disease-specific death. Subgroup analyses did not demonstrate improved disease-specific survival with radioactive iodine in patients ≥55 and in tumors >5 cm., Conclusion: Adjuvant radioactive iodine administration in classic papillary thyroid carcinoma >4 cm confined to the thyroid did not significantly impact disease-specific survival. Thus, these patients may not require routine treatment with adjuvant radioactive iodine., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Radiation-induced lung injury is a rare complication of radioactive iodine therapy (RAIT) in pediatric thyroid cancer treatment. In this case report, we describe a pediatric patient with an ERC1::RET-positive classic papillary thyroid carcinoma who developed progressive respiratory symptoms and chest imaging abnormalities following RAIT for lymph node and pulmonary disease., Case Presentation: A pediatric patient with ERC1::RET-positive classic papillary thyroid carcinoma was hospitalized for pulmonary decompensation 3 months following one empiric dose of RAIT. Testing revealed no evidence of infection or progression of pulmonary metastases, and there was no improvement with empiric antibiotic therapy for pneumonia. Despite empiric anti-inflammatory therapies, the patient remains symptomatic from a respiratory standpoint with requirement for supplemental oxygen and evidence of fibrotic changes on chest imaging., Conclusions: This patient's pulmonary condition is consistent with radiation-induced pulmonary injury including development of pulmonary fibrosis. With the availability of RET fusion-targeted inhibitors, this case highlights a rare pulmonary side effect of radioactive iodine for clinicians to recognize. Upfront targeted therapy protocols may help avoid radioactive iodine-associated adverse reactions., (© 2023 S. Karger AG, Basel.)

Background: To determine the effect of 131I treatment on postoperative parathyroid function and the timing of recovery of parathyroid function (RPF) in patients with protracted hypoPT., Methods: 260 patients with papillary thyroid cancer (PTC) were retrospectively analyzed, including 166 patients treated with radioactive iodine-131 (131I) classified into the 131I group and 94 patients without 131I treatment classified into the control group. Data on clinicopathological characteristics, demographics, dose and interval time of 131I treatment, number of parathyroid glands remaining in situ (PGRIS), occurrence of hypoPT, duration of RPF, preoperative and postoperative levels of Ca and PTH were collected., Results: The patients in the 131I group showed a higher persistent hypoPT rate than those in the control group ( p  = 0). The PGRIS and total number of PG were significantly higher in patients who recovered from protracted HypoPT ( p  = 0.02; p  = 0.03). PGRIS and 131I treatment [1 ∼ 2 VS 0, p  = 0.03, OR 3.19; 3 ∼ 4 VS 0, p  = 0.02, OR3.62; p  = 0.02, OR 1.98, respectively] were independent factors influencing postoperative persistent hypoPT. The timing of RPF differed significantly for patients in the control group compared to those in the 131I group [ p  = 0.00]., Conclusions: We found that 131I treatment significantly prolonged the RPF of patients with protracted hypoPT and caused late RPF (even beyond 12 months). The diagnosis of "permanent" hypoPT should be cautiously made at least 12 months after surgery, especially in patients who receive 131I treatment.

Purpose: Neutrophil-lymphocyte ratio (NLR), markers-lymphocyte-to-monocyte ratio (LMR), and platelet to-lymphocyte ratio (PLR) have potential roles as prognostic biomarkers in various cancers. The study was evaluated to investigate the predictive value of the peripheral inflammatory biomarkers in patients with papillary thyroid carcinoma (PTC) before radioiodine therapy to the response of clinical outcomes., Methods: We retrospectively analyzed the patients diagnosed with PTC at the Second Hospital of Shandong University between September 2018 and January 2020. Patients were divided into low and high inflammatory biomarker groups based on median values. The area under the receiver operating characteristic curves (ROC) and logistic regression were used to explore the potential risk factors., Results: A total of 692 patients were enrolled, which included 197 (28.4%) males and 495 (71.6%) females. The median values of NLR, LMR and PLR of these patients were 1.7 (range 0.3-5.7), 7.1 (range 1.1-23.4) and 137.6 (range 27.6-497.5), respectively, and the mean values were 1.95 ± 0.82, 7.4 ± 2.5 and 148.7 ± 54.8, respectively. Compared to the lower PLR group, the higher group was significantly associated with gender, tumor size, N stage and thyroglobulin level ( P <0.05). At the end of follow-up, 75.5% (523/692), 13.3% (91/692), 4.5% (31/692), and 6.7% (47/692) of patients were evaluated as excellent response (ER), indeterminate response (IDR), structural incomplete response (SIR), and biochemical incomplete response (BIR) respectively. In term of clinical outcomes, the NLR, LMR and PLR showed relatively low discriminative power ( P ≥0.05)., Conclusion: We found that higher PLR values was associated with poor clinicopathological features in PTC. However, the peripheral inflammatory indicators (NLR, LMR and PLR) may be insufficient to predict short-term clinical outcomes of patients with radioiodine therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, He, Li, Sun, Zhang, Li and Zhu.)

Aim: The aims of the study are to evaluate the predictive value of early post-operative stimulated thyroglobulin (sTg) analysis on the recurrence risk, and to define a cut-off value that is related to recurrence risk in low to intermediate risk papillary thyroid cancer (PTC)., Methods: This retrospective cohort study included individuals who were diagnosed with PTC aged 18 years or older and had been operated by experienced surgeons of a tertiary university hospital between the years 2011 and 2021. The American Thyroid Association thyroid cancer guidelines version 2015 was used as the risk stratification system. Early sTg measurement obtained at 3-4 weeks after surgery when TSH >30 µIU/mL. Data was collected from the hospital database. A total of 328 patients who had post-operative early sTg values with negative anti-Tg antibodies were included., Results: The median age was 44 years. Of the 328 patients, 223 (68%) were women. The median tumor diameter was 11 mm. One hundred ninety-one patients (58.2%) had low risk and 137 (41.8%) had intermediate risk for recurrent disease. Of the 328 patients, 4.0% had recurrent disease. In multivariate Cox regression, post-operative early sTg value [OR: 1.070 (1.038-1.116), P = .000], and the pre-operative malign cytology [OR: 1.483 (1.080-2.245), P = .042] were independent risk factors for recurrence. On the ROC curve analysis, the cut-off value of early sTg was 4.1 ng/mL for those with recurrent disease., Conclusion: This study demonstrated that early sTg could predict recurrent disease in patients with low to intermediate risk PTC. A cut-off of 4.1 ng/mL was identified with a high negative predictive value., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The effectiveness of iodine-131( 131 I) therapy in patients with papillary thyroid cancer (PTC) of various stage is controversial. This study aimed to use prognostic risk groups to guide 131 I therapy in patients with PTC after radical thyroidectomy., Methods: Data of 53,484 patients with PTC after radical thyroidectomy were collected from the Epidemiology and End Results (SEER) database. Patients were divided into subgroups according to MACIS system and regional lymph node involvement. The prognostic role of 131 I therapy was investigated by comparing Kaplan-Meier survival analysis and Cox proportional hazard models in different subgroups., Results: Sex, age, tumor size, invasion, regional lymph node involvement, and distant metastasis was related to the survival of patients with PTC. If MACIS < 7, 131 I treatment didn't affect the cancer-specific survival (CSS) rate. If MACIS ≥ 7, 131 I therapy didn't work on CSS rate for patients with N0 or N1a < 5 status; 131 I therapy had improved CSS rate for patients in the N1a ≥ 5 or N1b status. If patients with distant metastasis, invasion, or large tumor, 131 I therapy didn't improve CSS rate for patients in N0 or N1a < 5 stage., Conclusion: After radical thyroidectomy, if MACIS < 7, patients with PTC could avoid 131 I therapy. If MACIS ≥ 7, patients in the N0 or N1a < 5 could avoid 131 I therapy; those in the N1a ≥ 5 or N1b stage should be given 131 I therapy. Among them, all patients with distant metastasis should be given 131 I therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAF V600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18 F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations ( P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation ( P < 0.01). This association was not observed for BRAF V600E mutations ( P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Context: The waiting time for radioactive iodine therapy (WRAIT) after total thyroidectomy (TT) in patients with papillary thyroid cancer (PTC) and lymph node metastases (N1) has not been sufficiently investigated for risk of adverse outcomes., Objective: This work aimed to estimate the effect of WRAIT on the outcomes of disease persistence and recurrence among patients with N1 PTC and investigate factors predictive of delayed radioactive iodine therapy (RAIT)., Methods: This retrospective cohort study was conducted in a university hospital. A total of 909 patients with N1 PTC were referred for RAIT between 2014 and 2018. WRAIT is the duration between TT and initial RAIT. The optimal WRAIT threshold determined using recursive partitioning analysis was used to define early and delayed RAIT. The primary end point was tumor persistence/recurrence. We compared the outcomes of patients with early and delayed RAIT using inverse probability weighting based on the propensity score., Results: The WRAIT threshold that optimally differentiated worse long-term remission/excellent response outcomes was greater than 88 days (51% of our cohort; n = 464). WRAIT exceeding 88 days was associated with an augmented risk of disease persistence/recurrence (odds ratio, 2.47; 95% CI, 1.60-3.82) after adjustment. Predictors of delayed RAIT included residence in lower-income areas, reoperation before the initial RAIT, TT at a nonuniversity-affiliated hospital, multifocality, extrathyroidal extension, N1b disease, and pre-RAIT-stimulated thyroglobulin level less than 1 ng/mL., Conclusion: Delayed RAIT beyond 88 days after TT in patients with N1 PTC independently increased the risk of disease persistence/recurrence. Evaluation of the predictive determinants of prolonged WRAIT may help target at-risk patients and facilitate interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse., Materials and Methods: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis., Results: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion., Conclusions: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension., (© 2023. The Author(s) under exclusive licence to Japan Radiological Society.)

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

Background: The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated., Methods: DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching., Results: 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC., Conclusion: RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Zhang, Hu, Zhang, Huang and Shen.)

Background: Thyroid cancer is a very damaging disease. The most common treatment for this disease includes thyroidectomy and then using radioactive iodine (RAI). RAI has many side effects, including a decrease in salivary secretions, followed by dry mouth and oral and dental injuries, as well as increased inflammation and oxidative stress. Selenium can be effective in these patients by improving inflammation and oxidative stress and by modulating salivary secretions. So far, only one clinical trial has investigated the effect of selenium on thyroid cancer patients treated with radioiodine therapy (RIT) conducted on 16 patients; considering the importance of this issue, to show the potential efficacy of selenium in these patients, more high-quality trials with a larger sample size are warranted., Methods: This is a parallel double-blind randomized controlled clinical trial that includes 60 patients aged 20 to 65 years with papillary thyroid cancer (PTC) treated with RAI and will be conducted in Seyyed al-Shohada Center, an academic center for referral of patients to receive iodine, Isfahan, Iran. Thirty patients will receive 200 µg of selenium for 10 days (3 days before to 6 days after RAI treatment) and another 30 patients will receive a placebo for the same period. Sonographic findings of major salivary glands, salivary secretions, and sense of taste will be evaluated before and 6 months after 10-day supplementation., Discussion: Due to its anti-inflammatory and antioxidant effects, as well as improving salivary secretions, selenium may improve the symptoms of thyroid cancer treated with radioactive iodine. In past studies, selenium consumption has not reduced the therapeutic effects of radiation therapy, and at a dose of 300 to 500 μg/day, it has not had any significant side effects in many types of cancer under radiation therapy., Trial Registration: Iranian Registry of Clinical Trials IRCT20201129049534N6 . Registered on 16 September 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Context: Whether radioactive iodine therapy (RAIT) is necessary for intermediate-risk papillary thyroid cancer (PTC) after total thyroidectomy is still lacking reliable evidence, especially for patients with low postoperative thyroglobulin (Tg) levels., Objective: This study conducted a propensity score matching (PSM) analysis to investigate whether RAIT is effective in reducing the recurrence of intermediate-risk PTC with low Tg levels., Methods: In total, 1487 patients with intermediate-risk PTC with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL after total thyroidectomy were enrolled retrospectively. The clinicopathological characteristics were compared between the non-RAIT and RAIT groups before and after PSM (1:4 matching). The impact of RAIT on biochemical recurrence and structural recurrence was evaluated., Results: Overall, 1349 (90.7%) patients underwent RAIT, and 138 (9.3%) did not. After a median follow-up time of 51 months, 30 patients presented with recurrence, including 11 structural and 19 biochemical recurrences. After PSM, the non-RAIT group had a higher rate of structural recurrence (5/138 vs 5/552, P = .046) and biochemical recurrence (6/138 vs 4/552, P = .005) than the RAIT group. Multivariate analysis showed that not receiving RAIT was an independent risk factor for structural recurrence (hazard ratio [HR] 10.572, 95% CI 2.439-45.843, P = .002) and biochemical recurrence (HR 16.568, 95% CI 3.670-74.803, P < .001). Kaplan-Meier analysis showed that the non-RAIT group had more unfavorable recurrence-free survival (structural and biochemical, all P < .05)., Conclusion: RAIT could decrease the recurrence risk of intermediate-risk PTC in patients with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL. Further prospective randomized studies are needed to confirm these findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes., Purpose: To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131 I 1.11 GBq (30 mCi)., Methods: Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography., Results: Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up., Conclusions: Our findings support the recommendation against routine RA in low-risk DTC patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The role of adjuvant external-beam radiotherapy (EBRT) in the treatment of locally advanced papillary thyroid carcinoma (PTC) remains controversial due to the lack of prospective data and the conflicting retrospective data. This study aimed to determine the benefits of adjuvant EBRT in patients with PTC and other organ invasions using propensity score matching to reduce the heterogeneity of the patient population., Methods: Data from patients with PTC with other organ invasions but no distant metastases who underwent surgery and adjuvant radioactive iodine (RAI) alone (Non-EBRT group) or adjuvant EBRT plus RAI (EBRT group) were retrospectively reviewed. Propensity matching was used to reduce heterogeneity. Survival outcomes and toxicities associated with EBRT were evaluated., Results: Between January 2005 and December 2019, 102 patients in the Non-EBRT group and 26 patients in the EBRT group were evaluated. In the 48 propensity score-matched patients, no significant differences in baseline characteristics between the Non-EBRT and EBRT groups were detected. The locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were significantly higher in the EBRT group compared with the rates in the Non-EBRT group (5y-LRRFS: 100% vs. 74%, p = 0.003, 5y-RFS: 91% vs. 74%, p = 0.035). EBRT was well-tolerated, with no grade ≥ 3 toxicity, and all patients completed the therapy as planned., Conclusion: Adjuvant EBRT plus RAI exhibited acceptable toxicity and improved LRRFS and RFS in patients with PTC with other organ invasions compared with RAI alone., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Using response to surgery when tailoring radioiodine (RAI) therapy for papillary thyroid cancer (PTC) is valued but lacks prospective validation., Objective: To spare RAI thyroid remnant ablation among patients with intermediate-risk PTCs using 3-tiered assessments with response to surgery highlighted, in addition to the risk of the recurrence stratification and TNM staging., Methods: Patients with no evidence of disease (NED) identified as excellent response (ER) or indeterminate response (IDR) to surgery were spared from RAI thyroid remnant ablation after informed consent and prospectively enrolled under active surveillance. Those involved in other trials or without sufficient follow-up data were excluded. Dynamic responses were followed and compared longitudinally. The main outcome measures were NED presenting as durable ER or IDR for over 12 months., Results: Of the enrolled 215 patients, 47.4% (102/215) ER and 52.6% (113/215) IDR were identified regarding RAI decision-making. After a median of 23.6 (interquartile range 13.8-31.6) months, the share of ER increased to 82.8% (178/215) and IDR decreased to 16.3% (35/215), with 85 patients shifting from IDR to ER over time, only 0.5% (1/215) structural incomplete response and 0.5% (1/215) biochemical incomplete response observed. Successful remnant ablation was observed in 27.7% (26/94) of the patients completing 2 diagnostic whole-body scans after a median interval of 13.0 months, indicating a theranostic effect. In the 173 patients followed for over 12 months, the NED rate did not differ between ER and IDR subgroups (100% vs 97.9%, P = .20)., Conclusion: Through the 3-tiered assessments with response to surgery highlighted, postoperative ER and IDR spared from RAI remnant ablation may indicate similar favorable responses in intermediate-risk patients with PTC during 23.6 months of follow-up., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Chronic sialadenitis is the most common complication of radioactive iodine (RAI) treatment. The aim of the study was to ascertain sonographic features of the major salivary glands in patients with papillary thyroid cancer (PTC) treated with RAI., Methods: The database of a tertiary medical center was retrospectively searched for consecutive patients who underwent total thyroidectomy for PTC in 2011-2020 with ultrasound follow-up after 1 year. Changes in ultrasound features of the major salivary glands were compared between patients treated or not treated with RAI postoperatively., Results: The cohort included 158 patients, of whom 109 (69%) were treated postoperatively with RAI (mean dose, 131 mCi) and 49 were not (control group). Sonographic changes were observed in the major salivary glands in 43% of the study group and 18% of the control group (p = 0.002), including coarse echotexture, decreased echogenicity, fibrosis, and atrophy. Higher RAI doses were significantly correlated with the prevalence and severity of glandular changes (p < 0.0001)., Conclusion: RAI treatment following thyroidectomy is associated with a dose-response effect and adverse changes in the major salivary glands and should be prescribed carefully., Level of Evidence: 4 Laryngoscope, 133:1271-1275, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

This study aimed to assess the impact of adjuvant external beam radiotherapy (EBRT) on the survival of patients with locally invasive papillary thyroid carcinoma. This retrospective study used data from the Surveillance, Epidemiology, and End Results database for the diagnosis of papillary thyroid carcinoma, using Cox models to screen for adverse prognostic factors. The prognostic value of using adjuvant external beam radiotherapy in papillary thyroid carcinoma was further evaluated, based on the competing risk model and propensity score matching. Based on the competitive risk model, the sub-distribution hazard ratio (SHR) of the multivariate analysis of patients receiving EBRT alone versus those receiving radioiodine-131 alone was 9.301 (95% CI 5.99-14.44) (P < 0.001), and the SHR of the univariate analysis was 1.97 (95% CI 1.03-3.78) (P = 0.042). In the propensity score-matched Kaplan-Meier analysis, patients who received EBRT still had worse OS (6-year OS, 59.62% vs 74.6%; P < 0.001) and DSS (6-year DSS, 66.6% vs 78.2%; P < 0.001) than patients who did not receive EBRT. Patients who received EBRT had a higher cumulative risk of death due to thyroid cancer after PSM (P < 0.001). Adjuvant EBRT was not associated with survival benefit in the initial management of locally invasive papillary thyroid cancer., (© 2023. The Author(s).)

Purpose: Radioactive iodine ( 131 I) therapy is a conventional post-surgery treatment widely used for papillary thyroid carcinoma (PTC). Since 131 I is orally administered, we hypothesize that it may affect gut microbiome. This study aims to investigate alterations of intestinal microbiome caused by 131 I therapy in PTC patients and explore its association with response to 131 I therapy., Methods: Fecal samples of 60 PTC patients pre- and post- 131 I therapy were collected to characterize the 131 I therapy-induced gut microbiota alterations using 16S rRNA gene sequencing. According to the inclusion criteria, sequence data of 40 out of the 60 patients, divided into excellent response (ER) group and non-excellent response (NER) group, were recruited to investigate the possible connection between gut microbiota and response to 131 I therapy. Multivariate binary logistic regression was employed to construct a predictive model for response to 131 I therapy., Results: Microbial richness, diversity, and composition were tremendously altered by 131 I therapy. A significant decline of Firmicutes to Bacteroides (F/B) ratio was observed post- 131 I therapy. 131 I therapy also led to changes of gut microbiome-related metabolic pathways. Discrepancies in β diversity were found between ER and NER groups both pre- and post- 131 I therapy. Furthermore, a predictive model for response to 131 I therapy with a p value of 0.003 and an overall percentage correct of 80.0% was established, with three variables including lymph node metastasis, relative abundance of g&#95;Bifidobacterium and g&#95;Dorea. Among them, g&#95;Dorea was identified to be an in independent predictor of response to 131 I therapy (p = 0.04)., Conclusion: For the first time, the present study demonstrates the gut microbial dysbiosis caused by 131 I therapy in post-surgery PTC patients and reveals a previously undefined role of gut microbiome as predictor for 131 I ablation response. G&#95;Dorea and g&#95;Bifidobacterium may be potential targets for clinical intervention to improve response to 131 I in post-operative PTC patients., Trial Registration: ChiCTR2100048000. Registered 28 June 2021., (© 2022. The Author(s).)

Purpose: Papillary thyroid carcinoma (PTC) with other organ invasions is directly related to patient prognosis and quality of life; however, studies on the clinical outcomes of adjuvant radioactive iodine (RAI) for PTC with other organ invasions are limited. This study aimed to clarify the clinical outcomes and prognostic factors for patients with PTC with other organ invasions after adjuvant RAI., Methods: Patients with PTC with other organ invasions without distant metastases who underwent surgery and adjuvant RAI were retrospectively reviewed. We evaluated the initial responses based on the American Thyroid Association guidelines and survival rates. Prognostic factors for locoregional recurrence-free survival (LRRFS) were analyzed., Results: Between January 2005 and December 2019, 102 patients were included in the study. Their median age was 55 years. The median follow-up duration was 92 months (range; 30-231 months). The excellent response rate after RAI was 42%. The 7-year overall survival, LRRFS, and recurrence-free survival rates were 100%, 75%, and 75%, respectively. Metastatic lymph node size, resection margin status, and post-RAI suppressed thyroglobulin level were the independent prognostic factors for LRRFS., Conclusion: We demonstrated that 75% of patients with PTC with other organ invasions could achieve long-term survival without recurrence after adjuvant RAI. Future development of effective treatment strategies for large metastatic lymph nodes, gross residual tumors, and high serum thyroglobulin levels is warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

SPECT/CT is a powerful tool for assessing unexpected concentrations of radioiodine resulting from benign uptake in organs with sodium-iodide symporter (NIS) expression. We report a case of accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 5.5 GBq of 131Iodine. SPECT/CT images localized the focal tracer uptake in the nasolacrimal sac/duct likely due to nasolacrimal duct obstruction secondary to prior radioiodine or iodine therapies. Hybrid SPECT/CT allows precise anatomical localization and help differentiate benign mimics of disease, which can alter patient management.

Previously, we reported that an inverse agonist of estrogen-related receptor gamma (ERRγ), GSK5182, enhances sodium iodide (Na + /I - ) symporter (NIS) function through mitogen-activated protein (MAP) kinase signaling in anaplastic thyroid cancer cells. This finding helped us to further investigate the effects of GSK5182 on NIS function in papillary thyroid cancer (PTC) refractory to radioactive iodine (RAI) therapy. Herein, we report the effects of ERRγ on the regulation of NIS function in RAI-resistant PTC cells using GSK5182. RAI-refractory BCPAP cells were treated with GK5182 for 24 h at various concentrations, and radioiodine avidity was determined with or without potassium perchlorate (KClO 4 ) as an NIS inhibitor. We explored the effects of GSK5182 on ERRγ, the mitogen-activated protein (MAP) kinase pathway, and iodide metabolism-related genes. We examined whether the MAP pathway affected GSK5182-mediated NIS function using U0126, a selective MEK inhibitor. A clonogenic assay was performed to evaluate the cytotoxic effects of I-131. GSK5182 induced an increase in radioiodine avidity in a dose-dependent manner, and the enhanced uptake was completely inhibited by KClO 4 in BCPAP cells. We found that ERRγ was downregulated and phosphorylated extracellular signal-regulated kinase (ERK)1/2 was upregulated in BCPAP cells, with an increase in total and membranous NIS and iodide metabolism-related genes. MEK inhibitors reversed the increase in radioiodine avidity induced by GSK5182. Clonogenic examination revealed the lowest survival in cells treated with a combination of GSK5182 and I-131 compared to those treated with either GSK518 or I-131 alone. We demonstrate that an inverse agonist of ERRγ, GSK5182, enhances the function of NIS protein via the modulation of ERRγ and MAP kinase signaling, thereby leading to increased responsiveness to radioiodine in RAI-refractory papillary thyroid cancer cells.

Objective: To assess the diagnostic performance of initial post-therapeutic 131 I single-photon emission computed tomography/computed tomography (SPECT/CT) compared with that of reoperation in detecting residual lymph node metastasis (LNM)., Methods: Patients with iodine-avid LNM detected on the initial post-therapeutic 131 I SPECT/CT and who underwent reoperative dissection within 6 months were included. LNMs (numbers and locations) detected via both methods were compared. The American Thyroid Association dynamic risk stratification was performed for patients receiving second radioactive iodine therapy after reoperation., Results: Fifty-three patients with 95 iodine-avid LNMs detected by 131 I SPECT/CT were enrolled. Fifty-one (96.2%) patients had 212 LNMs confirmed by reoperation (P = .004). The sensitivity and specificity of 131 I SPECT/CT in detecting LNM were 44.8% (95/212) and 91.6% (87/95), respectively. The location frequency of residual LNMs found by 131 I SPECT/CT was similar to that of reoperation (P = .057). Thirty-two patients received a second radioactive iodine treatment, and 6 (18.8%) patients still had residual iodine-avid LNM on SPECT/CT. Therapeutic response was evaluated by American Thyroid Association dynamic risk stratification in 16 patients. The number of patients with structural incomplete response, biochemical incomplete response, indeterminate response, and excellent response was 4 (23.5%), 4 (23.5%), 5 (29.4%), and 3 (17.6%), respectively., Conclusion: 131 I SPECT/CT has high specificity but relatively low sensitivity in detecting all residual LNMs. Approximately 80% of patients were rendered structurally disease free after reoperation., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Context: Few studies have explored radioactive iodine-refractory (RAIR) disease in children, adolescents, and young adults with papillary thyroid cancer (CAYA-PTC)., Objective: This study systematically investigated the clinicopathologic characteristics and prognosis of CAYA-PTC with RAIR disease., Methods: Sixty-five patients with PTC aged ≤20 years were enrolled in this study, and all patients were confirmed to have pulmonary metastases. Clinicopathologic profiles were compared between the radioactive iodine-avid (RAIA) and RAIR groups. Univariate and multivariate regression analyses were performed to identify risk factors for RAIR status and progressive disease (PD). Gene alterations were detected in 17 patients., Results: Overall, 20 patients were included in the RAIR group, accounting for 30.8% (20/65) of all patients. No significant difference in pathologic characteristics was observed between patients aged <15 years and patients aged 15-20 years, but younger patients were more likely to develop RAIR disease (hazard ratio [HR] 3.500, 95% CI 1.134-10.803, P = .023). RET fusions were the most common genetic alterations in CAYA-PTC, but an association with RAIR disease was not detected (P = .210). RAIR disease (HR 10.008, 95% CI 2.427-41.268, P = .001) was identified as an independent predictor of PD. The Kaplan-Meier curve revealed a lower progression-free survival (PFS) and disease-specific survival (DSS) rate in the RAIR group than in the RAIA group (P < .001 and P = .039). Likewise, RAIR disease was a risk factor for unfavorable PFS in patients aged <15 years (P < .001)., Conclusion: RAIR disease occurs in one-third of CAYA-PTC with pulmonary metastases. Younger patients (aged < 15 years) are more susceptible to RAIR status, which leads to unfavorable PFS and DSS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Outpatient ablation therapy with low-dose radioactive iodine (RAI) is applied to non-low-risk papillary thyroid cancer patients due to a chronic shortage of inpatient RAI treatment wards in Japan. We used the maximum dosage available for outpatient therapy of 30 mCi of RAI for ablation and diagnostic (Dx) whole-body scintigraphy (WBS). This study aimed to examine the significance of the second dose of 30 mCi. DxWBS was performed 6 months after ablation, and assessment of success or failure was performed 12 months after ablation. A second WBS was performed in the remaining RAI accumulation cases in the neck on DxWBS. The criteria for successful ablation was negative cervical accumulation on WBS, thyroid stimulating hormone-suppressed thyroglobulin (sup-Tg) below 1.0 ng?/?mL, and no increase in thyroglobulin antibody (TgAb) level. At the time of DxWBS, 35?/?68 cases met the successful criteria, and 45 cases achieved success at assessment. Sup-Tg values decreased significantly after ablation and decreased further after DxWBS in successful ablation cases, whereas those were not changed in ablation failure cases. Findings indicated that RAI used in DxWBS had therapeutic effects. It makes sense to use 30 mCi for DxWBS, given the current difficulty of inpatient ablation therapy with high-dose RAI. J. Med. Invest. 70 : 17-21, February, 2023.

Purpose: This study investigated the relationship between BRAF V600E mutation of the primary tumor and radioiodine avidity in lung metastases (LMs) and then further evaluated the impact of BRAF V600E mutation and radioiodine avidity status on the prognosis of papillary thyroid cancer (PTC) with LMs., Methods: Ninety-four PTC patients with LMs after total thyroidectomy and cervical lymph node dissection between January 2012 and September 2021 were retrospectively included. All patients received BRAF V600E mutation examination of primary tumors and radioactive iodine (RAI) therapy. The therapeutic response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) assessments (version 1.1). For patients with target lesions, the response was divided into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD); for patients without target lesions, the response was divided into CR, non-CR/non-PD, and PD. In therapeutic response, PR and SD were classified as non-CR/non-PD for analysis. The chi-square test and logistic regression were used to analyze the impact factor on PD and mortality. Progression-free survival (PFS) and overall survival (OS) curves were constructed by the Kaplan-Meier method., Results: It was found that 21.2% (7/33) of patients with positive BRAF V600E mutation and 62.3% (38/61) of patients with negative BRAF V600E mutation had radioiodine-avid LMs (χ 2 = 14.484, p = 0.000). Patients with positive BRAF V600E mutation are more likely to lose radioiodine avidity; the odds ratios (ORs) were 5.323 (95% CI: 1.953-14.514, p = 0.001). Finally, 25 patients had PD, and six patients died; loss of radioiodine avidity was the independent predictor for PD, and the ORs were 10.207 (95% CI: 2.629-39.643, p = 0.001); BRAF V600E mutation status was not correlated with PD (p = 0.602), whether in the radioiodine avidity group (p = 1.000) or the non-radioiodine avidity group (p = 0.867). Similarly, BRAF V600E mutation status was not correlated with mortality; only loss of radioiodine avidity was the unfavorable factor associated with mortality in univariate analyses (p = 0.030)., Conclusion: Patients with LMs of PTC were more likely to lose radioiodine avidity when their primary tumor had positive BRAF V600E mutation; however, only radioiodine avidity and not BRAF V600E mutation status affected the clinical outcome of patients with lung metastatic PTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Qi, Tian, Dai, Tang and Huang.)

Purpose: Generally, the prognosis for papillary thyroid cancer (PTC) is favorable. However, the moderate risk involved warrants further evaluation. Hence, we investigated the clinical outcomes in patients with moderate-risk PTC following surgery and the first 131 I therapy, as well as the relevant factors that influence the therapeutic efficacy., Methods: Retrospective analyses of 175 patients with medium-risk PTC who visited the Second Affiliated Hospital of Chongqing Medical University from September 2017 to April 2019 were conducted. In according with the 2015 American Thyroid Association (ATA) guideline treatment response evaluation system, the patients were categorized into the following groups: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structurally incomplete response (SIR), of which IDR, BIR, and SIR were collectively referred to as the NER group. To compare the general clinical features between the 2 groups of patients, 2 independent samples t- tests, χ 2 test, and Mann-Whitney U- test were performed, followed by multivariate logistic regression analyses. With reference to the receiver operating characteristic (ROC) curve, the predicted value of ps-Tg to ER was evaluated, and the best cut-off value was determined. The subgroups with BRAF V600E test results were analyzed by χ 2 test only., Results: The treatment responses of 123 patients were ER, while those of 52 patients were NER. The differences in the maximum tumor diameter ( U = 2495.50), the amount of metastatic lymph nodes ( U = 2313.50), the size of metastatic lymph node ( U = 2113.50), the metastatic lymph node ratio ( U = 2111.50), metastatic lymph node location ( χ 2 = 9.20), and ps-Tg level ( U = 1011.00) were statistically significant. Multivariate regression analysis revealed that ps-Tg (OR = 1.209, 95% CI : 1.120-1.305) was an independent variable affecting ER. The cut-off value of ps-Tg for predicting ER was 6.915 ug/L, while its sensitivity and specificity were 69.2% and 89.4%, respectively., Conclusions: Patients with smaller tumor size, fewer lymph nodes, lower metastatic lymph node ratio, metastatic lymph nodes in the central region, smaller lymph node size, and ps-Tg <6.915 ug/L demonstrated better therapeutic effects after the initial treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Rao, Zheng, Huang, Fang, Xiong and Yuan.)

Objective: The BRAF V600E and TERT promoter mutations are well known to be associated with poor clinical outcomes of papillary thyroid cancer (PTC). Radioactive iodide (RAI)-refractory can be evaluated in advance of treatment, for which predictive biomarkers may be helpful. The present study is to analyze the correlation of both mutations with the curative effect of radioiodine therapy., Methods: A total of 126 patients who underwent RAI therapy from October 2016 to August 2019 were recruited. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The RAI response of patients was assessed as excellent response (ER) and RAI-refractory at the end of follow-up., Results: When dividing the 126 patients into 4 groups, the no mutation, only BRAF V600E mutation, only TERT promoter mutation, and coexistence of two mutation groups were found in 15.8%, 68.3%, 2.4%, and 13.5% patients. RAI-refractory was found in 52.9% (9/17) patients with the coexisting BRAF and TERT mutations. In logistic regression analysis, M1, BRAF, and TERT mutation were confirmed to be independent factors predicting the RAI-refractory. Moreover, 35.3%, 41.2%, and 23.5% of patients in the BRAF and TERT mutation group were assessed as ER, SIR, and BIR respectively. Kaplan-Meier analyses revealed that the genetic duet of BRAF V600E and TERT promoter mutations was associated with a lower ER reached time., Conclusions: We found that BRAF V600E and TERT promoter mutation is significantly correlated with the poor curative effect of RAI therapy in PTC., Trial Registration: ClinicalTrials.gov Identifier: ChiCTR1800018760., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)