Background Changes in thyrotropin receptor antibody (TRAb) levels are associated with the clinical outcomes of Graves’ hyperthyroidism. However, the effects of the patterns of TRAb changes on patient prognosis according to the treatment duration of antithyroid drugs (ATDs) are not well established.
Methods In this retrospective cohort study, 1,235 patients with Graves’ hyperthyroidism who were treated with ATDs for more than 12 months were included. Patients were divided into two groups according to treatment duration: group 1 (12–24 months) and group 2 (>24 months). Risk prediction models comprising age, sex, and either TRAb levels at ATD withdrawal (model A) or patterns of TRAb changes (model B) were compared.
Results The median treatment duration in groups 1 (n=667, 54%) and 2 (n=568, 46%) was 17.3 and 37.1 months, respectively. The recurrence rate was significantly higher in group 2 (47.9%) than in group 1 (41.4%, P=0.025). Group 2 had significantly more goiter, thyroid eye disease, and fluctuating and smoldering type of TRAb pattern compared with group 1 (all P<0.001). The patterns of TRAb changes were an independent risk factor for recurrence after adjusting for other confounding factors in all patients, except in group 1. Integrated discrimination improvement and net reclassification improvement analyses showed that model B performed better than model A in all patients, except in group 1.
Conclusion The dynamic risk model, including the patterns of TRAb changes, was more suitable for predicting prognosis in patients with Graves’ hyperthyroidism who underwent longer ATD treatment duration.
Background Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers.
Methods This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers.
Results No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039).
Conclusion Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.
Background Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER).
Methods Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data.
Results The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group.
Conclusion The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.
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Background In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, –17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, –16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.
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Background The association between Graves’ disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography.
Methods Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules).
Results Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020).
Conclusion The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.
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Background Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis.
Methods This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009.
Results The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS).
Conclusion The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nation-wide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging.
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Background Serum calcitonin measurement contains various clinical and methodological aspects. Its reference level is wide and unclear despite sensitive calcitonin kits are available. This study aimed to identify the specific reference range in the healthy Korean adults.
Methods Subjects were ≥20 years with available calcitonin (measured by a two-site immunoradiometric assay) data by a routine health checkup. Three groups were defined as all eligible subjects (group 1, n=10,566); subjects without self or family history of thyroid disease (group 2, n=5,152); and subjects without chronic kidney disease, autoimmune thyroid disease, medication of proton pump inhibitor/H2 blocker/steroid, or other malignancies (group 3, n=4,638).
Results This study included 6,341 male and 4,225 female subjects. Males had higher mean calcitonin than females (2.3 pg/mL vs. 1.9 pg/mL, P<0.001) in group 1. This gender difference remained similar in groups 2 and 3. Calcitonin according to age or body mass index was not significant in both genders. Higher calcitonin in smoking than nonsmoking men was observed but not in women. Sixty-nine subjects had calcitonin higher than the upper reference limit (10 pg/mL) and 64 of them had factors associated with hypercalcitoninemia besides medullary thyroid cancer. Our study suggests the reference intervals for men who were non, ex-, current smokers, and women (irrespective of smoking status) as <5.7, <7.1, <7.9, and <3.6 pg/mL, respectively.
Conclusion Specific calcitonin reference range should be provided considering for sex and smoking status. Taking account for several factors known to induce hypercalcitoninemia can help interpret the gray zone of moderately elevated calcitonin.
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Background A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.
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Background The clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.
Methods We included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (<90 days) and the delayed (≥90 days) RRA groups based on the interval between TT and RRA. The results of diagnostic whole-body scan (DxWBS), ongoing risk stratification (ORS; response to therapy), and disease-free survival (DFS) were evaluated before and after propensity score matching (PSM).
Results Among the 526 patients, 75 (14.3%) patients underwent delayed RRA; they had more cervical lymph node metastasis and received a higher RRA dose than those who underwent early RRA. The median follow-up period was 9.1 years after initial therapy, and the structural recurrence rate was 1.9%. In DxWBS, 60 patients had focal iodine uptake limited in operative bed, with no significant difference between groups. According to ORS, 78%, 20%, 1%, and 1% patients were classified into excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. There was no significant difference in ORS or DFS between groups before and after PSM.
Conclusion The timing of the first RRA had no clinical impact in patients with low-risk PTC. Thus, the clinical decision for RRA can be determined >3 months after TT considering other prognostic factors.
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Background The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC).
Methods This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS).
Results In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS.
Conclusion WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.
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Background The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI.
Methods We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology.
Results Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351).
Conclusion There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.
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