Thyroid最新文献

Objectives: Cytologically indeterminate thyroid nodules (Bethesda class III or IV) carry a 10-40% risk of malignancy. Diagnostic lobectomies are frequently performed but negative surgeries incur unnecessary costs on the healthcare system, potential complications, and negative impacts on quality of life. Molecular tests (MTs) have been developed to reduce unnecessary surgeries. However, well-validated, high-performance MTs are often expensive, and their cost-effectiveness has not been studied in the Asian population. This study evaluates the rate of unnecessary surgery in the setting without MT (our current practice) and the cost-effectiveness of introducing a commercially available MT for the management of cytologically indeterminate thyroid nodules in a modernized city in Asia. Methods: Management decisions and outcomes of consecutive Bethesda III or IV thyroid nodules in a tertiary endocrine surgery center in Hong Kong were evaluated. Costs of health service provided by the public health system, which covers >90% of healthcare service in the city, were retrieved. A decision tree model was developed to compare the cost-effectiveness in avoiding unnecessary surgeries of current practice versus routine MT from a public healthcare provider's perspective. In our current practice, MT was not available, and patients with indeterminate nodules received either upfront lobectomy, repeat fine needle aspiration cytology (FNAC), or active surveillance. Results: Over a 4-year period, 2157 FNACs were performed. After exclusion, 1957 FNACs were analyzed, and 18.6% were Bethesda III or IV. Thirty-six percent of these cytologically indeterminate nodules received upfront surgery, with 28% having malignancy in final pathology, that is, 72% of surgeries were unnecessary. Routine MT could reduce 82 unnecessary surgeries/year, 26% more than current practice. Routine MT resulted in an incremental cost-effectiveness ratio of Hong Kong dollar (HKD) 49,102 (US dollar [USD] 6314) per unnecessary surgery. Sensitivity analysis showed test cost of MT contributed significantly to incremental cost-effectiveness ratio. Lowering the commercial price of MT to below HKD 8044 (USD 1031) would render routine MT cost-saving. Conclusion: Currently, a high rate of unnecessary surgeries is being performed for cytologically indeterminate thyroid nodules. MT was more effective in reducing unnecessary surgeries than current practice, but at a higher cost. MT will become cost-saving if the test cost could be lowered.

Aim: The study aimed to analyze the long-term outcomes of [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer therapy in individuals diagnosed with radioiodine-resistant (RAI-R) follicular cell-derived thyroid cancer. Materials and Methods: In this retrospective study, 73 patients with RAI-R follicular thyroid carcinoma who had undergone multiple lines of previous treatments were included. Following [⁶⁸Ga]Ga-DOTA.SA.FAPi positron emission tomography-computed tomography scan, among the 73 patients, 65 received [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer monotherapy with a median activity of 5.5 GBq per cycle at 8-week intervals. The remaining eight patients underwent tandem [¹⁷⁷Lu]Lu/[²²⁵Ac]Ac-DOTAGA.FAPi dimer therapy, consisting of a median of two cycles of [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer followed by one cycle of [²²⁵Ac]Ac-DOTAGA.FAPi dimer, also at 8-week intervals. The primary endpoint included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included PERCIST criteria response assessment and safety assessment according to Common Terminology Criteria for Adverse Events (V5.0). Results: We enrolled 37 female and 36 male patients, with a mean age of 54.3 years (range: 27 - 80 years). The patients received a median cumulative activity of 22.2 GBq (range, 4 GBq-55.5 GBq) of [¹⁷⁷Lu]Lu-DOTAGA-FAPi dimer over one to nine cycles, with a median of three cycles. Among 73 patients, 20 died and 16 deaths were due to thyroid cancer. Nineteen patients experienced disease progression, with an estimated median PFS of 29 months [CI 14-34 months]. The estimated median OS was 32 months [CI 21-40 months]. Four patients (5.4%) encountered grade III anemia, primarily linked to bone metastasis in three cases and neck tumor mass bleed in one. Grade III thrombocytopenia occurred in three patients (4%). No grade III renal or hepatotoxicity was observed. Conclusion: In this study, [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer therapy showed promising safety and efficacy in aggressive, radioiodine-resistant thyroid cancer, achieving a median PFS and OS of 29 and 32 months, respectively, with manageable adverse events. Confirmation of our findings is needed from prospective clinical trials comparing [¹⁷⁷Lu]Lu-DOTAGA.FAPi dimer therapy to other treatments.

Background: The longest reported follow-up for thermal ablation of papillary thyroid microcarcinoma (PTMC) is 5 years. We evaluated the long-term efficacy and safety of radiofrequency ablation (RFA) in patients with low-risk PTMC with clinical follow-up of more than 10 years. Methods: In this retrospective cohort study, we included patients with low-risk PTMC who had more than 10 years of follow-up after ultrasound (US)-guided RFA (performed between May 2008 and December 2013). Sixty-five consecutive patients with 71 low-risk PTMCs who were unsuitable for surgery or declined surgery were included. Before RFA, all patients underwent US and thyroid computerized tomography. Repeat RFA for staged ablation was performed when the first RFA did not secure sufficient safety margins because of the tumor closely abutting the recurrent laryngeal nerve. Follow-up US imaging was performed at 1 week, 3 months, 6 months, every 6 months until 2 years, and then annually afterward. Primary outcomes were the respective cumulative rates of disease progression (defined by local tumor progression, lymph node, or distant metastasis), newly developed thyroid cancer, and conversion surgery. Secondary outcomes were serial volume reduction rate (VRR), complete disappearance rate of ablated PTMC, and adverse events associated with procedures. Results: Of 65 patients included in the study, 60 had unifocal and 5 had multifocal PTMCs. The mean number of RFA sessions per tumor was 1.2, and the median follow-up duration was 151 months (interquartile ranges, 131-157). Twenty percent (13/65) of patients required repeat RFA. There were no cases of disease progression. Five patients (5/65, 7.7%) developed a new papillary thyroid cancer (four treated with RFA and one with lobectomy). At 24 months, the mean VRR was 100%, and this was maintained throughout the final follow-up. The complete tumor disappearance rates after one or more RFA treatments were 40.8% (29/71), 74.6% (53/71), and 100% (71/71) at 6, 12, and 24 months, respectively. One major (subclinical hypothyroidism) and three minor adverse events occurred. Conclusions: In our experience, RFA of low-risk PTMC is effective and safe. During more than 10 years of follow-up, we observed no incident local tumor progression nor metastases, but 7.7% of patients developed a new papillary thyroid cancer.

Background: Levothyroxine to suppress thyrotropin (TSH) to <0.5 mIU/L following thyroidectomy in differentiated thyroid cancer (DTC) may reduce recurrence in higher-risk DTC. However, there is limited evidence to support guideline recommendations to maintain TSH in the low-normal range of 0.5-2 mIU/L to reduce recurrence in patients with lower risk DTC. The primary objective was to assess the association between exposure to high normal serum TSH (2-4 mIU/L) as compared with low normal TSH (0.5-2 mIU/L) target ranges and cancer recurrence in patients with DTC after thyroidectomy. Methods: This population-based retrospective cohort study used linked, administrative health care databases from Ontario, Canada, to follow patients with DTC post-thyroidectomy from 2007 to 2018. The exposure was time updated, serum TSH, treated as a cumulative and instantaneous exposure. Multivariable cause-specific proportional hazard regression analyses were performed to determine time to DTC recurrence from index date, defined as a composite of repeat neck surgery, radioactive iodine (RAI) treatment, and/or DTC-specific death. Results were also stratified by initial treatment as a marker of baseline recurrence risk in a sensitivity analysis. Results: This cohort of 26,336 individuals (78% female) with DTC and a median age of 50 years were followed for a median of 5.9 (interquartile range 3.6-8.6) years; 40.9% were initially treated with a hemi-thyroidectomy only and 38.2% received a total thyroidectomy and RAI. Compared with exposure to TSH 0.5 to ≤2 mIU/L, DTC recurrence rate was similar for each additional 3 months of exposure to TSH >2 to ≤4 mIU/L (adjusted cause specific [cs] hazard ratio [HR] 0.99 [confidence interval or CI 0.97-1.02]) but was significantly increased with each additional 3 months of exposure to TSH >4 mIU/L (adjusted csHR 1.07 [CI 1.04-1.09]). Results were similar across baseline treatment groups. Conclusion: There was no difference in clinically significant recurrence in those with low-risk DTC maintained with a TSH of 0.5-2 mIU/L compared with 2-4 mIU/L. Guidelines should consider liberalizing target TSH level post thyroidectomy in low-risk cohorts. These results cannot be applied to patients with high-risk DTC.

Background: Statin use is reported to reduce the risk of Graves' orbitopathy (GO) in Western populations. However, study regarding the protective effect of statins against GO in Asians with Graves' disease (GD) is scarce. This study aims to investigate the efficacy of statins in preventing GO in Asian GD patients. Materials and Methods: This nationwide, population-based retrospective cohort study used data from beneficiaries aged >40 years diagnosed with GD from the National Health Insurance Research Database (NHIRD) from 2010 to 2020. The International Classification of Diseases codes, Anatomical Therapeutic Chemical codes, and the surgery/procedure codes derived from the NHIRD were used to obtain the information on GD, GO, and statin use. Propensity score (PS) analysis with matching and inverse probability of treatment weighting analysis (IPTW) was conducted to minimize confounding. The Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to compare the risk of GO among statin users and nonusers. Results: The final analysis included 102,858 patients; 7,073 were statin users (62.9 ± 10.6 years, 29.7% male), and 95,785 were nonusers (53.6 ± 10.4 years, 25.7% male). The crude incidence rate of GO among statin users and nonusers was 5.00‰ versus 6.75‰ and 4.91‰ versus 5.15‰ for the overall population and population after PS matching method, respectively. The Cox regression analysis showed that statin users had a significantly lower risk of GO (adjusted hazard ratio [HR] after PS matching 0.79, 95% confidence interval [CI]: 0.63-0.99, p = 0.037; adjusted HR after IPTW method: 0.64, CI: 0.51-0.79, p < 0.001). The risk of GO was not different among users of different kinds of statins (i.e., atorvastatin, rosuvastatin, pitavastatin, and other statins) or among different intensities of statins (low-to-moderate intensity vs. high intensity). Conclusions: The use of statins in Asian GD patients was associated with a reduced risk of GO. In addition, the risk of developing GO among users of commonly prescribed statins or users of different intensities of statins was not significantly different.

Background: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine malignancy. The utility of ultrasound (US) surveillance after initial treatment has not been clearly delineated. We sought to evaluate the clinical utility of US for the detection of residual or recurrent disease in pediatric patients with thyroid cancer beginning 1 year after initial therapy. Methods: This is a retrospective cohort study of pediatric patients (<19 years) diagnosed with DTC between 1998 and 2022 whose response to therapy (RTT) one year after initial treatment (thyroidectomy ± radioactive iodine) was excellent or indeterminate. We evaluated the association between sonographic and biochemical findings (thyroglobulin [Tg] and Tg antibodies [TgAb]) at one year with the subsequent diagnosis of residual/recurrent structural disease in the neck (SDN). Results: In total, 112 patients had 1-year RTT that was excellent (n = 61, 54.5%) or indeterminate (n = 51, 45.5%). Median length of subsequent follow-up was 6.4 (interquartile range 3.8-8.9) years. Overall, 683 surveillance neck US were performed, with a mean ± standard deviation of 1.0 ± 0.4 US per patient per year. Of 61 patients with excellent RTT, none developed SDN during follow-up. Eighteen patients (29.5%) had a false-positive indeterminate or abnormal US finding. Of 51 patients with indeterminate RTT, 9 (17.6%) developed SDN during follow-up. SDN was detected by US in 7/9 cases (77.8%). SDN was detected by I-123 scan, but not by US, in two cases (22.2%), both with abnormal Tg/TgAb. 7/9 (77.8%) cases of SDN were detectable by Tg/TgAb. Overall, fine-needle aspiration (FNA) was performed in 17/112 (15.2%) patients and diagnosed SDN in six patients. Overall, 11/112 patients (9.8%) underwent FNA but were not diagnosed with SDN. Conclusions: In pediatric DTC patients with excellent response to initial therapy, the utility of serial US surveillance is limited by the low risk of SDN and frequent false-positive US findings. In children with indeterminate RTT, SDN occurs in a significant proportion and may be detected by US or by abnormal Tg/TgAb levels. These patients may benefit from the combination of US and biochemical surveillance.

Background: Tumor-infiltrating lymphocytes (TILs) are a protective prognostic factor in several solid tumors and predict response to immune checkpoint inhibitor therapy. The prognostic impact of TILs in medullary thyroid cancer (MTC) is poorly understood. Materials and Methods: In this retrospective cohort study, we assessed the TILs profile of primary MTC tumors using the International TILs Working Group system and correlated this with clinicopathological prognostic variables, including the International Medullary Thyroid Cancer Grading System (IMTCGS) grade and survival outcomes. Results: We identified 71 patients with primary MTC tumors who were treated surgically between 1995 and 2016 at the Royal North Shore Hospital in Sydney, Australia. The median (interquartile range) duration of follow-up was 69 (90) months. Using the ITWG system, all patients with MTC had low TILs, with a median (range) of 3% (0-10%). This group was further subdivided into "very low" (0-4%) and "low" (5-10%), and on Cox regression analysis, increasing TILs were associated with increased local recurrence (log-rank p = 0.022, odds ratio [OR] 1.94 [confidence interval or CI 0.61-6.16], p = 0.26), reduced disease-specific survival (log-rank p = 0.015, OR 5.11 [CI 1.01-26.0], p = 0.049), and a trend to decreased distant metastasis-free survival (log-rank p = 0.14). When examining the association between TILs and other prognostic factors, only "high IMTCGS grade" was significantly associated with increased TILs (OR 7.29 [CI 1.21-43.90], p = 0.015). In the multivariable logistic regression analysis, there was no significant association between TILs and local recurrence or disease-specific survival. Conclusions: In our study, the prognostic value of TILs in MTC was limited. Even high-grade MTC can be considered an immune quiescent tumor, and the adverse prognostic factors associated with higher grade tumors outweigh the marginal increase in immune recognition associated with a slight increase in TILs. The low level of TILs in MTC and their lack of correlation with survival suggest that immune checkpoint inhibitor therapy may not be effective.

Background: Although patients with anaplastic thyroid cancer (ATC) generally have a poor prognosis and there are currently no effective treatment options, survival and response to therapy vary between patients. Genomic and transcriptomic profiles of ATC have been reported; however, a comprehensive study of the tumor microenvironment (TME) of ATC is still lacking. This study aimed to elucidate the TME characteristics associated with ATC and their prognostic implications. Methods: We analyzed bulk RNA transcriptomic data from 1,634 samples-including 476 normal thyroid tissues, 25 benign thyroid adenomas, 340 RAS-like and 719 BRAF^V600E-like differentiated thyroid cancers (DTC-R and DTC-B, respectively), and 74 ATCs. We assessed the TME and molecular characteristics of these thyroid cancer subtypes using deconvolution analysis. Results: The TME of ATC was characterized by a high abundance of immune cells and fibroblasts and a low abundance of epithelial cells compared to other thyroid histologies. During its malignant evolution, ATC exhibited an ecotype more closely related to DTC-B than RAS-like DTC (DTC-R). Furthermore, we identified two distinct molecular subtypes within ATC with significant differences in their TMEs. We termed the subtype with increased immune cells and fibroblasts as ATC-immune-fibroblast (ATC-IF) and the subtype with elevated epithelial and endothelial cells as ATC-epithelial-endothelial (ATC-E). The ATC-IF group had worse disease-specific survival (log-rank p = 0.035), higher ERK scores, and lower thyroid differentiation scores than the ATC-E group. While both ATC subtypes had elevated immune cells and fibroblasts compared to DTC-R and DTC-B, this increase was more pronounced in ATC-IF, with a marked rise in myeloid lineage cells and promigratory fibroblasts. Immune checkpoint gene expression and epithelial-mesenchymal transition scores were significantly higher in the ATC-IF group than in the ATC-E group. Conclusion: ATC shows a TME distinct from that of DTC and can be further divided into two molecular subtypes-each with its own unique TME. The ATC-IF group, with a poorer prognosis and higher ERK score, is enriched in immune cells and fibroblasts, which may represent potential therapeutic targets.