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Objectives: We introduced selpercatinib prior to radioactive iodine therapy prior to radioactive iodine therapy (RAI) for pediatric papillary thyroid cancer (PTC) to enhance the tumorical effects of RAI., Case Presentation: PTC has an excellent prognosis but is commonly associated with local and distant metastases. Successful complete response to the current standard of care, thyroidectomy with lymph node resection and RAI, is achieved in only a small minority of cases with metastases. The direct effect of tyrosine kinase inhibitors (TKIs) on tumor regression has been confirmed in several randomized controlled studies, while the increased RAI uptake has been reported in small case series, but typically TKIs are currently reserved third-line. Selpercatinib is a TKI that specifically has a durable effect in RET-fusion positive malignancies. We describe a 10-year-old Hispanic girl with metastatic PTC treated with total thyroidectomy and extensive lymph node resection. Evaluation for relevant genetic drivers of the malignancy revealed a strong overexpression of the RET tyrosine kinase domain indicative of a RET gene fusion. Selpercatinib 120 mg twice daily given orally was initiated prior to the initial dose of RAI to achieve further tumor regression by a direct cytostatic effect and then secondarily enhancement of RAI uptake. Minimal side effects occurred, specifically intermittent mild skin rashes that resolved. Resolution of distal lung metastases was noted on CT imaging. RAI was then administered 9 months afterward, with ultimately achievement of a low thyroglobulin level 1.0 ng/mL 11 months after RAI., Conclusions: In conclusion, selpercatinib given prior to the initial dose of adjunctive RAI for RET-fusion positive PTC is a well-tolerated intervention that further reduces tumor burden and potentially enhances the tumorcidal effects of RAI., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

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.)

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: 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).)

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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.)

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.)

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.)

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.)

The study was to evaluate the effect of radioactive iodine (RAI) treatment application time and clinical, histopathological factors on ablation success in patients with operated papillary thyroid cancer (PTC) in low and intermediate-risk. One hundred sixty-one patients with PTC in the low and intermediate-risk were evaluated. Most patients (89.4%) were in the low-risk, and 10.6% were in the intermediate-risk. When the patients were divided into two groups according to the date of receiving RAI treatment after surgery, those who received early treatment (≤3 months) constituted the majority of the patients (72.7%). Seventeen patients received 1.85 Gigabecquerel (GBq), 119 3.7 GBq, 25 5.55 GBq RAI. Most patients (82%) achieved ablation success after the first RAI treatment. The time interval between surgery and RAI treatment did not affect ablation success. Stimulated Tg level measured on the RAI treatment day was an independent predictive factor for successful ablation (p<0.001). The cut-off value of Tg found to predict ablation failure was 5.86 ng/ml. It was concluded that 5.55 GBq RAI treatment could predict ablation success compared to 1.85 GBq dose (p=0.017). It was concluded that having a T1 tumor may predict treatment success compared to a T2 or T3 tumor (p=0.001, p<0.001, retrospectively). The time interval does not affect ablation success in low and intermediate-risk PTC. The ablation success rate may decrease in patients who receive low-dose RAI and have high Tg levels before treatment. The most crucial factor in achieving ablation success is giving enough doses of RAI to ablate the residual tissue., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Encapsulated papillary carcinoma (EPC) is a rare malignant papillary breast cancer accounting for approximately .5%-2% of all breast tumors. The aim of this multicenter study was to evaluate clinicopathologic features of EPC in addition to oncological outcomes and radiotherapy (RT) details., Methods: From 10 different academic hospitals in Turkey, we obtained pathology reports of 80 patients with histologically confirmed EPC between 2005 and 2022. Demographic, diagnostic, and treatment data were collected from medical records, retrospectively. Local failure, distant progression, toxicity-adverse effects, overall survival (OS), and disease-free survival were evaluated, and survival analyzes were performed using the Kaplan-Meier method., Results: Eighty patients with the diagnosis of misspelled sorry (ECP) were retrospectively evaluated. The median age of the patients was 63 (range, 35-85). After a median follow-up of 48 (range; 6-206) months, local recurrence was observed in three patients (4%). Local recurrence was less common in the patients who received whole breast RT with a tumour bed boost (p = .025). There were not any distant metastasis or disease-related death. RT was applied to 61% of the cases, and no treatment-related grade 3 or higher toxicity was reported in any of the patients. Five year OS, cancer-specific survival (CSS), and  were observed as 85%, 100%, and 96%, respectively., Conclusions: ECP is a rare, slow-progressing breast carcinoma associated with good prognosis, it is a disease of elderly patient, and usually occurs in postmenopausal women. It responds extremely well to optimal local treatments and appropriate adjuvant treatments on a patient basis, and has excellent OS and CSS ratios., (© 2022 John Wiley & Sons Australia, Ltd.)

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.)

Background: The BRAF V600E mutation (BRAF mut) in papillary thyroid cancer (PTC) has been associated with poor response to therapy with 131 I in patients with metastases but the results in postsurgical treatment are controversial. Our main objective is to investigate the impact of the mutation on the biokinetics of the administered 131 I therapy after surgery., Methods: A prospective study was designed, from July 2015 to January 2018 which included patients with PTC receiving 131 I therapy after surgical treatment. To study the biokinetics of the radioiodine in postoperative thyroid remnants, SPECT-CT images were acquired so as to obtain the following variables: percentage of remnant uptake at 2 and 7 days post-administration, effective half-life and time-integrated activity coefficient. All of them were compared depending on the mutational diagnosis and other clinical features and pathological variables., Results: Sixty-one patients, and in total 103 thyroid remnants, were included. About 59% of patients were BRAF mutated. The mutation was associated with classic variant (88.5% vs. 11.5%; P=0.0001), desmoplastic reaction (85.7% vs. 14.3%; P=0.002), smaller tumor size (1.5 vs. 2.1 cm; P=0.024), nodal disease (3.3 vs. 1; P=0.001) and advanced stages (76.9% vs. 23%; P=0.014). The BRAFmut group had a lower percentage of 131 I uptake at 2 days (0.17% vs. 0.47%; P=0.001) and at 7 days (0.02% vs. 0.1%; P=0.013); and a lower time-integrated activity coefficient (0.05h vs. 0.17 h; P=0.002). In univariate analysis, in addition to the mutation, the histological variant was significant but only for time-integrated activity coefficient (P=0.04). In multivariate analysis, only mutation determined the 2-day uptake (P<0.001) and the time-integrated activity coefficient (P<0.001)., Conclusions: The BRAF V600E mutation is associated with lower 131 I uptake in thyroid remnants. Furthermore, it is an independent factor that decreases the effect of post-surgical 131 I therapy, and therefore, it could be used as a potential tool to optimize the treatment of PTC.

Differentiated thyroid cancer (DTC) is the most frequent endocrine neoplasm, with an increase in recent decades. Papillary carcinoma is the most frequent histological subtype and a large number of cases are related to tumors of small size and with little clinical repercussion, detected incidentally or as a consequence of the availability of diagnostic techniques. The "good prognosis" of the majority of cases has maintained for years the controversy in the approach to these patients, especially in two basic aspects of the therapeutic protocol: surgery and the administration of radioiodine. While in metastatic and high-risk patients, the administration of 131 I therapy is widely accepted, in intermediate-low risk patients its use is highly questioned. In this paper we review the available evidence on radioiodine therapy in low-risk patients., (Copyright © 2022. Published by Elsevier España, S.L.U.)

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.)

The potential overtreatment of patients with papillary thyroid microcarcinoma (MPTC) has been an important clinical problem in endocrine oncology over the past decade. At the same time, current clinical guidelines tend to consider prior radiation exposure as a contraindication to less extensive surgery, even for low-risk thyroid carcinomas, which primarily include microcarcinomas. This study aims to determine whether there are differences in the behavior of MPTC of two etiological forms (radiogenic and sporadic), including invasive properties, clinical data, and recurrence in patients aged up to 30 years. For this purpose, 136 radiogenic (from patients aged up to 18 years at the time of the Chornobyl accident) and 83 sporadic (from patients born after the Chornobyl accident) MPTCs were selected and compared using univariate and multivariate statistical methods in a whole group and in age and tumor size subgroups. No evidence of more aggressive clinical and histopathological behavior of radiogenic MPTCs as compared to sporadic tumors for basic structural, invasive characteristics, treatment options, and postoperative follow-up results was found. Moreover, radiogenic MPTCs were characterized by the lower frequencies of oncocytic changes (OR = 0.392, p = 0.004), nodal disease (OR = 0.509, p = 0.050), and more frequent complete remission (excellent response) after radioiodine therapy (OR = 9.174, p = 0.008). These results strongly suggest that internal irradiation does not affect tumor phenotype, does not associate with more pronounced invasive properties, and does not worsen prognosis in pediatric or young adult patients with MPTC, implying that radiation history may be not a pivotal factor for determining treatment strategy in such patients., 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 Bogdanova, Chernyshov, Zurnadzhy, Rogounovitch, Mitsutake, Tronko, Ito, Bolgov, Masiuk, Yamashita and Saenko.)

Context: Obesity has been reported as a potential risk factor for the aggressiveness of papillary thyroid cancer (PTC), but the data gathered so far are conflicting., Objective: The aim of our study was to evaluate the relationship between body mass index (BMI) and aggressiveness of PTC at the diagnosis and clinical outcome., Methods: A total of 337 patients who underwent radioactive iodine (RAI) therapy between March 2017 and May 2020 were recruited. Patients were divided into four groups: underweight (BMI<18.5 kg/m 2 ), normal weight (18.5-24.9 kg/m 2 ), overweight (25-29.9 kg/m 2 ), and obese (BMI≥ 30 kg/m 2 ). Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines., Results: This study included 337 patients with PTC (71.5% women, median age 45.21 ± 13.04 years). The mean BMI was 24.2 ± 3.1 kg/m 2 . Obese groups had a higher age than the other groups (P = 0.001). Moreover, obese patients had larger tumor sizes and higher T stage, compared to overweight, normal weight, and underweight patients (P = 0.007). After a median follow-up of 32 months, 279 patients (82.7%) had achieved an excellent response (ER) to therapy. The overall ER rates were compared between groups, and they did not differ significantly., Conclusions: We demonstrated that BMI may have an additive effect on the aggressiveness of PTC, but did not have an effect on the response to therapy after high-dose RAI 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 © 2022 Cao, Zhu, Sun, Li, Yun and Zhang.)

Objective: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC)., Patients: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients., Results: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026)., Conclusions: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors., (© 2021 John Wiley & Sons Ltd.)

Background: Papillary thyroid cancer (PTC) is commonly associated with neck lymph node metastasis (LNM), and recurrence does occur after radioactive iodine (RAI) ablation therapy. This study aimed to analyze the effectiveness of RAI ablation with regard to disease recurrence in intermediate-risk PTC patients with neck LNM. In addition, the study identified possible predisposing risk factors that might benefit from RAI ablation and analyzed common RAI therapy complications among these patients., Methods: A retrospective analysis of 349 intermediate-risk PTC patients with neck LNM who underwent thyroidectomy with neck dissection was performed. The oncologic results and clinicopathologic characteristics of these patients together with the incidence of postoperative RAI therapy complications were evaluated., Results: Of the 349 patients, disease recurrence after treatment occurred for 27 patients (8%) during a mean follow-up period of 58.7 months (range 7-133 months). The recurrence-free survival curve of the patients who received postoperative RAI therapy (n = 208) did not differ significantly from that of the patients who did not receive it (n = 141) (P = 0.567). Nine patients without adjuvant RAI therapy (6%, 9/141) had recurrence. The recurrence rate for the central LNM patients without RAI therapy was only 2% (2/106). Both of these patients with recurrence had pathologic extranodal spread (ENS) and a high number (> 5) of metastatic central LNs. Postoperative RAI-related complications were observed in 24 patients (12%)., Conclusions: Postoperative RAI is not necessary for intermediate-risk papillary thyroid cancer patients with central LNM, especially for patients with negative ENS and low number (< 5) of metastatic lymph nodes., (© 2021. Society of Surgical Oncology.)

Objective: This study aimed to evaluate the feasibility and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) in the treatment of low-risk papillary thyroid microcarcinoma (PTMC), and to observe the histopathological changes after MWA., Methods: MWA was performed under ultrasound guidance for 73 unifocal PTMC patients without clinically cervical or distant metastasis. The target ablation zone exceeded the tumor edge (judged by contrast-enhanced US) to avoid marginal residue and recurrence. Ultrasound evaluation was performed at 1 day, 1, 3, 6, 12 and 24 months after treatment, and thyroid function evaluation at the first 6 months. Repeated fine needle aspiration cytology or core needle biopsy pathology was performed at 3 or 6 months after MWA to evaluate residual tumors. Any adverse event associated with MWA was evaluated., Results: The follow-up after MWA lasted 6 (6, 12) months. Tumor volume decreased significantly from 0.06 mm 3 (0.04, 0.11 mm 3 ) to 0.03 mm 3 (0.00, 0.06 mm 3 ) at 12 months after MWA ( P < 0.001), with a median volume reduction ratio of 80.28% (-7.43, 100%) and 16 cases (21.92%) presenting complete remission. The largest diameter, volume and ablation energy were found to be different in patients with and without complete remission 12 months after MWA. On histopathological examinations, no atypical or malignant follicular cells were identified after thermal ablation. The most common pathological characteristics were fibroblastic proliferation (34/39, 87.18%) and chronic inflammation (32/39, 82.05%), followed by infarction (21/39, 53.85%). Five patients were transferred to thyroidectomy and 4 of them were confirmed with local recurrence and/or lymph node metastasis. Serum thyrotropin decreased transiently after MWA ( P < 0.01) but normalized thereafter. No serious and permanent complications were reported., Conclusions: MWA is a safe and effective treatment for low-risk PTMC. Fibroblastic proliferation and chronic inflammation are the most common pathological changes after MWA of PTMC., 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 © 2021 Lu, Li, Chu, Li, Li, Wang, Wang, Xu, Chen, Xu and Liu.)

Objectives: To evaluate the role of adjuvant radiation therapy in patients with locoregionally recurrent (rpT4/N1b) papillary thyroid carcinoma (PTC)., Methods: The medical records of patients with rpT4/N1b PTC who were treated between January 2001 and December 2016 were reviewed. A total of 57 patients were analyzed, of which 24 patients were treated with adjuvant radiation therapy, and 33 patients did not receive adjuvant radiation therapy. Survival outcomes were compared between the 2 treatment groups. The primary endpoint was locoregional recurrence-free survival rate., Results: The median follow-up period for all patients was 10.3 years (range, 2.8-19.2 years). The 15-year locoregional recurrence-free survival rate was 80.5% for those who received adjuvant radiation therapy and 28.1% for those who did not ( p <0.001). The 15-year distant metastasis-free survival rate was 48.8% for those who received adjuvant radiation therapy and 33.4% for those who did not ( p =0.906). The 15-year overall survival rate was 69.7% for those who received adjuvant radiation therapy and 53.1% for those who did not ( p =0.921)., Conclusions: Adjuvant radiation therapy ensured favorable locoregional recurrence-free survival in patients with rT4/N1b PTC and might contribute to improving patients' quality of life by reducing the need for additional salvage surgery and the economic burden of other salvage treatments, such as surgery or radioactive iodine therapy., (Copyright: © Saudi Medical Journal.)

Background: A diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management., Methods: Patients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression., Results: In 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 - 63.8), TSH <53.4 mU/L (OR 19.64, 95% CI: 4.94-78.13), thyroglobulin ≥50.0 ng/L (OR 7.4, 95% CI: 1.6-34.9) and free T4 ≥4.75 pmol/L (OR 156.8, 95% CI: 128.4-864.2)., Conclusion: The Dx scan can potentially change clinical management before treatment with I-131, but the yield is low. A Dx-scan should only be considered for patients with a high pre-scan risk of a change in management, based on patient history and prior center-based surgical outcomes., 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 © 2021 van der Boom, Zandee, Dekkers, van der Horst-Schrivers, Jansen, Kruijff, Brouwers and Links.)

Purpose: We speculated that radioiodine remnant ablation (RRA) could be performed less frequently in differentiated thyroid cancer (DTC) patients, if the recommendations of the 2018 Italian Consensus (ITA) were applied in clinical practice. Therefore, we compared the ITA indications for RRA with the recommendations by the 2015 American Thyroid Association guidelines (ATA)., Methods: We retrospectively evaluated 380 consecutive DTC patients treated with surgery and RRA, followed at the Section of Endocrinology, University of Siena, Italy from January 2006 to December 2019., Results: Using ITA a significant increase of DTC patients classified as low or high risk and a significant decrease of patients defined at intermediate risk were observed (p < 0.0001). Consequently, the percentage of patients without routinary indication for RRA (47.4%, versus 38.2%, p < 0.0001) and those with a definite indication for RRA (8.2 versus 1.8%, p < 0.0001) was significantly higher compared to ATA. Moreover, using ITA the percentage of patients with a selective use of RRA was lower in comparison to ATA (44.7% versus 60%, p < 0.0001). Nevertheless, the prevalence of distant metastases, at post-ablative whole body scan, in patients without indication for RRA, was not different using either ATA or ITA (2.1% and 1.1% respectively, p = 0.37)., Conclusion: The use of ITA Consensus, in clinical practice, increases significantly the number of patients for whom RRA is not routinely indicated in comparison to ATA guidelines but without differences in delaying the diagnosis of distant metastatic disease.

Background: The study evaluated the recurrence rate in patients with papillary thyroid carcinoma (PTC) and clinically apparent lymph node metastases (LNM) (cN1) who had low thyroglobulin (Tg) after total thyroidectomy and who were not submitted to adjuvant therapy with 131 I., Methods: This was a prospective study. It included 82 cN1 patients (≤3 LNM ≤1.5 cm without macroscopic extracapsular extension) with tumors ≤4 cm without macroscopic extrathyroid invasion (T1-2) and who after thyroidectomy had unstimulated Tg (u-Tg) < 0.3 ng/ml, negative antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) showing no anomalies. The patients were not submitted to therapy with 131 I., Results: The time of follow-up ranged from 24 to 156 months (median 84 months). Seventy-nine patients (96.3%) continued to have u-Tg < 0.3 ng/ml and negative US. Three patients (3.6%) exhibited an increase in Tg and structural recurrence was detected in two. After treatment, these patients achieved u-Tg < 1 ng/ml and the imaging methods revealed no apparent tumor., Conclusions: The results suggest that even cN1 patients, given the absence of extensive LNM or other adverse findings, who have low Tg and neck US showing no anomalies after thyroidectomy do not require radioiodine.

Radioiodine therapy with 131 I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131 I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131 I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan ® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131 I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131 I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.

Background: Most patients with papillary thyroid cancer (PTC) and lymph node metastases (LNM) undergoing reoperation do not show apparent disease after this procedure, but serum thyroglobulin (Tg) continues to be elevated in part of them. This study evaluated adjuvant therapy with 131 I in these patients., Methods: Patients with PTC and LNM diagnosed after initial therapy were selected. Patients undergoing reoperation and those without apparent disease after this procedure, but with nonstimulated Tg ≥1 ng/ml 6 months after reoperation, were included. The first 25 patients were submitted to therapy with 131 I (groups A) and the subsequent 30 patients did not receive this therapy (group B)., Results: Groups A and B were similar. During further follow-up, 21 patients developed structural disease and 34 continued without detectable disease (eight achieved complete remission). The outcomes were similar in groups A and B. Patients with Tg reduction >50% after reoperation tended to have a lower risk of recurrence (22.7 versus 48.5%), notably distant metastases (0 versus 15.1%), and were more likely to achieve complete remission (28 versus 3%). Patients with LNM FDG-positive had a higher risk of recurrence (54.5 versus 11.7%) and were less likely to achieve complete remission (3 versus 29.4%) after reoperation., Conclusion: Our results suggest that therapy with 131 I apparently does not prevent recurrences among patients who continue to have elevated Tg after neck reoperation. Further studies involving these patients are necessary, especially those who are at high risk of recurrence.

Rationale: The unpredictability of thyroid cancer can be striking, as the disease may rapidly progress to death in some individuals. Herein, we reported a rare case of aggressive papillary thyroid cell carcinoma (PTC) in an elderly patient de-differentiated into squamous cell carcinoma (SCC)., Patient Concerns: We describe a case of a 79-year-old Thai woman presented with hoarseness and neck mass for 2 months and she had been diagnosed with a 3-cm papillary thyroid carcinoma (PTC) in the right side of the thyroid gland. Later on PTC de-differentiated into SCC within 3 years after initial presentation., Diagnosis: De-differentiation from papillary thyroid carcinoma to squamous cell carcinoma., Interventions: The patient underwent a total thyroidectomy at the initial hospital and received high dose radioactive iodine (RAI) treatment at our hospital 1 month following the surgery and then was lost to follow-up. Two years later she came back with new development of right solid-cystic neck mass which was found to be recurrent PTC. A radical neck dissection was done and another high dose RAI treatment was given. However, she developed recurrent mass with tenderness at the site above previous solid cystic mass 6 months later. Re-exploration of the neck mass revealed an inflamed midline mass 2 cm with enlarged right lateral cervical lymph nodes., Outcomes: A histopathological examination of the midline neck mass showed poorly differentiated SCC with lymphatic invasion. The intermingling of two morphologically distinct tumors, a typical PTC and a poorly differentiated SCC, had been identified in 1 out of 14 excised cervical lymph nodes. The patient underwent external beam radiation without chemotherapy. She is still in stable condition at 18 months post-treatment., Lessons: This case clearly demonstrated that SCC transformed from a pre-existing PTC. The clinician should consider a possible transformation of papillary thyroid cancer into more aggressive histological types in elderly patients who present with rapidly progressive clinical behavior. However, some patients could have long-term survival if the tumor did not transform into anaplastic thyroid cancer.

Differentiated thyroid cancer is generally accompanied by a long term survival. However, in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

Introduction and Objectives: Radioiodine is the principal treatment for differentiated thyroid carcinomas. The aim of this study is to present our experience in the management of these tumours., Material and Method: We present a retrospective study of 55 patients operated for differentiated thyroid carcinoma in our hospital between 2007 and 2011., Results: The mean age at time of diagnosis was 49 years, and females predominated (78% of cases). Seventy eight percent of the patients were in the initial stages (stages i and ii). The definitive histopathological diagnosis was papillary carcinoma in 84% and follicular carcinoma in the remaining 16%. All of the patients, with the exception of 2 (4%), underwent total thyroidectomy, with lymphadenectomy in 58% of cases. Nine percent of the patients had permanent hypoparathyroidism and although 18% suffered transitory unilateral paralysis, 40% of these female patients had completely recovered after 6 months. Eighty-nine percent of the patients were given radioiodine postoperatively. There was a recurrence rate of 40% most of which was at cervical level (29% of the patients). Survival at 5 years was 87%, 95% of the papillary subtype, falling to 56% of the follicular subtype (P=.001)., Discussion/conclusions: The prognosis for differentiated thyroid carcinomas is excellent after appropriate surgical treatment, thorough preoperative assessment,and strict postoperative follow-up due to the significant recurrence rates., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

The worldwide incidence of thyroid cancer is increasing. A third of new thyroid cancer cases are papillary thyroid microcarcinoma (PTM), which are 1 cm or less. These tumors are mostly indolent with excellent prognosis. Although thyroid surgery is the most common management option for patients with PTM, new management options demand that treatment decisions must be individualized and based on patient's preference, context, and biology. This article describes management options for PTM patients and shared decision-making as a novel method for individualizing care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Standard treatment of differentiated thyroid cancer includes total thyroidectomy and high-dose Radioactive Iodine Therapy (RIT) for ablation of remnant thyroid tissue. When administered systemically, RIT can cause radiation-induced damage in non-targeted normal tissues. The aim of the present study was to compare the protective effects of amifostine (AMI), LCarnitine (LC), and Vitamin E (EVIT) against high dose radioactive iodine treatment induced Salivary Gland (SG) damage using SG scintigraphy and histopathological examination., Methods: Forty adult guinea pigs were studied. Twenty guinea pigs receive 555-660 MBq 131Iodine intraperitoneally (IP) to ablate the thyroid and impair the parenchymal function of the SGs. The animals were divided into eight groups as follows: (1) Group 1 (control): 1 mL IP PS (physiological saline); (2) Group 2: single dose of 200 mg/kg IP AMI one hour prior to 1 mL IP PS; (3) Group 3: 200 mg/kg IP LC and 1 mL IP PS for 10 days; (4) Group 4: 40 mg/kg intramuscular (IM) EVITand 1 mL IP PS for 10 days; (5) Group 5: IP RIT after premedication; (6) Group 6: Single dose of 200 mg/kg IP AMI one hour prior to RIT and IP RIT after premedication; (7) Group 7: IP RIT after premedication and 200 mg/kg IP LC for 10 days starting one day before RIT; and (8) Group 8: IP RIT after premedication and 40 mg/kg IM EVIT for 10 days starting one day before RIT. Scintigraphy was performed 1 month after treatment. SGs were examined by light microscopy and a histopathological scoring system was used to assess the degree of SG damage., Results: There were significant differences in the body weight and thyroid hormone levels between the groups after treatment., Conclusion: The individual use of AMI, LC and EVIT for radioprotection yield different levels of protection against radioactive iodine treatment injury in SGs; however, none of the agents could provide absolute protection at the doses administered in this experimental model., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Preclinical studies showed that BRAF mutation significantly reduced radioiodine uptake and decreased the sensitivity to radioactive iodine (RAI) therapy. However, clinical data regarding its role in therapeutic decision making with respect to RAI therapy are currently insufficient. Thus, this study aimed to evaluate the effect of BRAF mutation on the clinical response to RAI therapy for papillary thyroid microcarcinoma (PTMC) with intermediate-risk to high-risk features., Patients and Methods: From January 2012 and October 2015, consecutive patients with PTMC with intermediate-risk to high-risk features who underwent RAI therapy were retrospectively included. The data about BRAF mutation status were also obtained. The association between clinicopathological characteristics and mutation was investigated. After a median follow-up of 40 months, the clinical response to RAI therapy was also compared between positive and negative mutation groups., Results: A total of 236 patients were included, of whom 147 (62.3%) had positive mutation. The clinicopathological features did not show significant correlation with BRAF mutation status except the sex, extrathytoidal extension and T stage. Patients with PTMC with BRAF mutation showed an increased likelihood of having advanced T stage and extrathyroidal extension. In addition, this mutation did not affect the clinical outcome of RAI therapy., Conclusion: The status of BRAF mutation may not affect the clinical response to RAI therapy for patients with PTMC with intermediate-risk to high-risk features. More trials examining the role of BRAF mutation in guiding postoperative RAI therapy are needed.

Introduction: BRAFV600E activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAFV600E mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure., Material and Methods: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAFV600E mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised thatBRAFV600E mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012)., Results: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed betweenBRAFV600E mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p = 0.002), vascular invasion (p = 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related withBRAFV600E mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%)., Conclusion: We revealed that BRAFV600E mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAFV600E.

Purpose: To evaluate the safety and efficiency of microwave ablation (MWA) with low power of 20 w, respectively, in the treatment of cervical metastatic lymph node (CMLN) from papillary thyroid carcinoma (PTC) with a mean of 32-month follow-up., Methods: Eleven patients in total with 24 cervical lymph nodes (LNs) diagnosed with CMLN from PTC underwent MWA at a power of 20 w. We recorded images of the LNs under ultrasound first before MWA and 1, 3, 6, 12, months after MWA, and then every 6 months, respectively. The volumes of the LNs were compared before MWA and at each follow-up point after MWA. The thyroglobulin (Tg) test was performed before MWA and 3 months after MWA., Results: All patients were successfully treated, and they showed no major complications. Before MWA, the mean volume of the LNs was 364.15 ± 306.89 mm 3 , which decreased to 234.10 ± 230.34 mm 3 , 107.51 ± 129.47 mm 3 , 20.88 ± 39.27 mm 3 , 3.38 ± 12.74 mm 3 , and completely disappeared at the follow-up point of 1, 3, 6, 12, and 18 months after MWA, respectively. The mean Tg was 11.81 ± 7.50 ng/ml, a data significantly decreased to 0.43 ± 0.11 ng/ml 3 months after MWA (P = 0.000). In the follow-up period, no recurrent lesions were found., Conclusions: For the treatment of CMLN from PTC, low power MWA showed good safety and efficacy. MWA is likely to be a candidate for patients with high risks or who refuse reoperation.

Objective: To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis., Design and Methods: This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding., Results: In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAF V600E -positive (P = 0.324) subgroups., Conclusions: Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAF V600E , lymph node metastases, or unfavorable thyroglobulin levels.

A 72-year-old man underwent total thyroidectomy and radioiodine remnant ablation for papillary thyroid cancer in 2016. The posttherapy whole-body scan showed uptake in the neck, classified as residual thyroid tissue. Two years later, the patient came to our observation to perform a second radioiodine therapy for high levels of thyroglobulin. The planar posttherapy scan showed a focal radioiodine area in the neck. SPECT/CT diagnosed a voluminous esophageal diverticulum located in the upper third of the esophagus. A CT performed to discover the source of thyroglobulin excluded locoregional or distant metastases and confirmed the presence of a Zenker diverticulum.

Purpose: Papillary thyroid carcinoma (PTC) with pulmonary metastases is rare in children and adolescents. Unlike adults, limited data are available on children with this disease. Thus, this study evaluated the therapeutic efficacy and prognostic factors of individuals less than 21 years of age with pulmonary metastases from PTC., Methods: Seventy-six children and adolescents with pulmonary metastases from PTC treated with 131 I were retrospectively analyzed. Therapeutic efficacy was evaluated by changes in serum thyroglobulin (Tg) and chest computed tomography (CT). Factors predictive of progression-free survival and overall survival were measured by the Kaplan-Meier method., Results: Among the 76 patients included in this study, 22.4% (17 of 76) were less than 15 years old and 65.8% (50 of 76) were female. Under the evaluation of stimulated serum Tg levels, RAI treatment were effective in 55.9% (38 of 68), stable in 26.5% (18 of 68) and ineffectvie in 17.6% (12 of 68) of patients. Changes on anatomical imaging suggested complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 8.5, 62.0, 15.5, and 14.1% of individuals, respectively. Univariate analysis showed that size and tumor doubling time of pulmonary metastases were independent factors affecting therapeutic efficacy. Extra-thyroidal extension, tumor diameter of pulmonary metastases and tumor doubling time were significant independent factors regarding progression-free survival rates, while only tumor doubling time and tumor diameter were significant risk factors associated with overall survival rate., Conclusions: Radioactive iodine therapy is an effective treatment for children and adolescents with pulmonary metastases from PTC. Extra-thyroid extension was associated with disease progression while did not show significant influence on overall survival. Tumor doubling time and tumor diameter were the main factors influencing both progression-free survival and overall survival.

Context: Many differentiated thyroid cancers (DTC) dedifferentiate and become radioactive iodine (RAI)-refractory (RAIR) with worse outcomes. Targeted therapy (TTx) may downregulate MAPK signaling and sensitize tumors to RAI., Objective: We describe patients with RAIR DTC receiving TTx with demonstrated RAI uptake allowing for iodine-131 (I131) administration., Design: Charts of patients with metastatic, progressive, RAIR DTC in whom TTx increased RAI uptake on a diagnostic whole-body scan (WBS), were reviewed. Results of WBS, I131 administration, thyroglobulin (TG) panels, and cross-sectional studies were recorded., Setting: Thirteen patients [median age (range), 56 (45 to 75) years; seven men] were included; 11 (85%) had DTC, two (15%) had poorly DTC. Nine (69%) had BRAF mutations, three (23%) had RAS mutations, and one (8%) was wild type. Selective BRAF or an MEK inhibitor TTx was continued for a median (range) of 14.3 (1 to 76.4) months before diagnostic WBS., Results: Nine (69%) patients were treated with I131 [median (range) activity, 204.4 (150 to 253) mCi], after which TTx was discontinued. Median (range) follow-up was 8.3 (0 to 17.4) months after I131 therapy. All nine patients had durable disease control (three had partial response, six had stable disease). TG and TG antibody levels increased in patients who demonstrated uptake before TTx, and declined in eight of the nine patients after I131 treatment. Adverse events included pneumonitis and sialadenitis., Conclusion: TTx in BRAF-/RAS-mutated RAIR DTC resensitizes tumors to iodine. Subsequent I131 administration results in meaningful responses. Patient selection, adverse events, response duration, and survival impact require additional study.

Objective: To correlate clinical and pathological characteristics at diagnosis with patient long-term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC)., Study Design: Retrospective analysis of clinical and pathological prognostic factors of 124 paediatric patients with DTC (age at diagnosis <19 years) followed up for 10.4 ± 8.4 years. Patients with a follow-up >3 years (n = 104) were re-classified 18 months after surgery on the basis of their response to therapy (ongoing risk stratification)., Results: Most patients had a papillary histotype (96.0%), were older than 15 years (75.0%) and were diagnosed because of clinical local symptoms (63.7%). Persistent/recurrent disease was present in 31.5% of cases during follow-up, but at the last evaluation, only 12.9% had biochemical or structural disease. The presence of metastases in the lymph nodes of the lateral compartment (OR 3.2, 95% CI, 1.28-7.16, P = 0.01) was the only independent factor associated with recurrent/persistent disease during follow-up. At the last evaluation, biochemical/structural disease was associated with node metastases (N1a, N1b) by univariate but not multivariate analysis. Ongoing risk stratification compared to the initial risk classification method better identified patients with a lower probability of persistent/recurrent disease (NPV = 100%)., Conclusions: In spite of the aggressive presentations at diagnosis, paediatric patients with DTC show an excellent response to treatment and often a favourable outcome. N1b status should be considered a strong predictor of persistent/recurrent disease which, as in adults, is better predicted by ongoing risk stratification., (© 2018 Wiley Periodicals, Inc.)

Objectives: The efficacy of radioiodine remnant ablation (RRA) for patients with differentiated thyroid carcinoma (DTC) with gross extrathyroidal extension (ETE) is well described in observational studies. However, its role in gross ETE invading only strap muscles, T3b category in the newly proposed eighth edition of the TNM staging system, is currently unknown., Methods: This study retrospectively analyzed 260 DTC patients with ETE invading only strap muscles who underwent thyroidectomy at a tertiary Korean hospital between 1994 and 2005. Cancer-specific survival (CSS) and recurrence-free survival (RFS) in the no RRA (n = 13), low RRA activity (<3.7 GBq, n = 80), and high RRA activity (≥3.7 GBq, n = 167) groups were studied., Results: No significant differences were observed between low and high activity RRA groups in terms of 10-year CSS (97.3% versus 99.3%; HR 0.23, 95% CI 0.02-2.57; p = .235) and RFS (86.8% versus 88.8%; 0.90, 0.40-2.03; p = .804). In the no RRA group, no patients died of cancer, and only one developed structural recurrence. In Cox regression analyses with inverse probability of treatment weighting adjusted for clinicopathologic risk factors, high activity RRA was not related to recurrence outcomes compared to low activity (HR 0.60, 95% CI 0.26-1.35; p = .214)., Conclusions: Long term oncologic outcomes did not significantly differ between low versus high activity RRA groups, which suggests that low activity RRA might be sufficient in patients with DTC with gross ETE invading only strap muscles. Further studies are needed to clarify the optimal activity of RRA in these patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the value of dynamic changes of midkine (MK) to monitor post-surgical patients with papillary thyroid cancer (PTC) who were managed with I therapies.MK concentration at initial I ablation therapy (MK1) as well as 10 to 12 months thereafter (MK2) was evaluated. And the dynamic changes of thyroglobulin (Tg) were compared (Tg1 and Tg2). Patients with MK influencing co-morbidities and with positive thyroglobulin antibodies were excluded. Concentrations of MK were measured by enzyme-linked immunosorbent assay.There were 241 PTC patients (36 males, 205 females) enrolled, 55 cases had metastases (8 males, 47 females) during their follow-up. Cox regression showed if Tg2 decreased (compared with Tg1), but not to less than 1.0ng/mL under TSH stimulation, the risk of metastases was 12.554 times more than if it could decrease to the optimal level. If Tg2 increased, the risk is 19.461 times higher. As for MK, if MK2 level decreased (compared with MK1), but not to a normal level, the risk of metastases is 3.006. If MK2 level increased, it would be 5.030 likely to had metastases.Our results indicated that MK could potentially be used as a disease monitoring biomarker for PTC, although inferior to Tg.

Objective: To investigate the influential factors of efficacy of the first (131)I ablation therapy for thyroid remnant in papillary thyroid microcarcinoma (PTMC) patients after thyroidectomy. Methods: Eighty-nine PTMC patients who underwent twice (131)I ablation therapy and (131)I whole body follow-up scan ((131)I-WBS) within 5 to 8 months in our department from September 2007 to October 2016 were identified and enrolled in present study. Patients were divided into complete-ablation group and uncomplete-ablation group according to whether or not radioactivity was detected at the thyroid bed in (131)I-WBS. The χ (2) test and multi-variance Binary logistic regression were performed for the factors which might affect the therapeutic efficacy. Results: The first (131)I ablation therapy was successful in 41 of 89 patients (46.07%). Residual thyroid weight was found to be associated with therapeutic efficacy ( P <0.05), while gender, age, surgical method, lesions'maximum diameter, with or without LN metastasis, with or without distant metastasis, time of operation from first (131)I treatment, lesions'number, thyroid stimulating hormone (TSH), thyroglobulin (Tg), the consistency of (131)I-WBS and (99)Tc(m)-pertechnatate, TNM stage, ATA risk, Tg/TSH ratio were not significant associated with therapeutic efficacy. Binary logistic regression analysis was performed in these respects and it indicated that residual thyroid weight and ATA risk were not statistically significant independent variable ( P >0.05). Conclusions: Residual thyroid weight might affect efficacy of the first (131)I ablation therapy on thyroid remnant in PTMC patients after thyroidectomy, but it is not an independent factor. Multiple interrelated factors should be considered when predicting the efficacy of the first (131)I ablation therapy.

Background: Papillary thyroid microcarcinoma (PTMC) has high incidence and low disease-specific mortality. However, active surveillance is not accepted by most patients owing to high physical or psychological pressures. The emergence of ablation technologies is supplanting traditional surgery. Our goal was to compare the clinical outcomes of microwave ablation (MWA) and surgery for T1aN0M0 PTMC., Methods: A total of 92 consecutive patients with T1aN0M0 PTMC were studied retrospectively. Forty-six patients had been treated with MWA, and the other 46 had undergone surgery. MWA was performed using extensive ablation extending from the nodule's lower pole to the upper pole. Surgery was performed by total thyroidectomy or thyroid lobectomy. We compared the two groups in terms of mean length of stay, cost, mean blood loss, surgical incision, operating room (OR) time, quality of life (QOL) assessment, complications, and therapeutic efficacy over a follow-up period of 42 months., Results: The mean length of stay, cost, mean blood loss, surgical incisions, OR time, and complications in the MWA group were significantly lower than those of the surgery group. The QOL after MWA was higher than it was after surgery. The nodule volume decreased significantly from 53.61 ± 48.43 mm 3 to 4.84 ± 6.55 mm 3 (p < .001) at the 42-month follow-up, exhibiting a percentage volume reduction of 81.33 ± 36.87%. No recurrence or metastasis occurred in either group during the follow-up period., Conclusions: MWA may be considered a minimally invasive alternative to surgery for solitary T1aN0M0 PTMC with low incidence of complications and good therapeutic effect.

An elderly woman presented with an enlarging left breast lump. Breast imaging revealed a large suspicious mass associated with cystic components. Core biopsy however was non-diagnostic and only revealed necrotic papillary tissue. The patient then underwent excision of the lesion that revealed a large area of intracystic papillary ductal carcinoma in situ with a focus of micropapillary variant of mucinous cancer. This case describes how this rare subtype could present as necrotic papillary tissue on core biopsy, resulting in a diagnostic dilemma, which had not been previously reported. A literature review of this rare subtype was performed too., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)