Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer.

Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07-0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48-17.34]; Group 3: PD-L1- and thyroid irAE- : 30.49 [6.60-140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor-Node-Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.

Comparison of Patient-Reported Outcomes Between Active Surveillance and Immediate Lobectomy in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS Cohort.

Background: Patients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan. Methods: The multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter. Results: A total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, confidence interval [CI] 1.02-1.05, p < 0.001), smaller tumor size (OR 0.78, CI 0.69-0.87, p < 0.001), family history of thyroid cancer (OR 1.48, CI 1.03-2.12, p = 0.035), prior awareness of AS (OR 1.53, CI 1.16-2.02, p = 0.003), and higher income (OR 1.79, CI 1.13-2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9-43.9) in the AS group and 28.7 months (20.4-44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared with the Lobectomy group (ß 0.17, CI 0.02-0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p = 0.592). Conclusions: This study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months. Clinical Trial Registration: KCT0004935.

Structural Modification Effect of Se-doped Porous Carbon for Hydrogen Evolution Coupled Selective Electrooxidation of Ethylene Glycol to Value-added Glycolic Acid.

The ethylene glycol oxidation reaction (EGOR) has attracted attention because ethylene glycol (EG), which exhibits large-scale production and a low market price, can be reformed into valuable glycolic acid (GCA) with the cogeneration of high-purity hydrogen gas during the reaction. In this study, a noble catalyst material of Pt nanoparticles supported on Se-doped porous carbon (Pt/SePC) is prepared and investigated for the selective electrochemical oxidation of EG to GCA. Pt/SePC achieved a maximum EG conversion of 94.6% and GCA selectivity of 84.4% and maintained this high performance with negligible degradation during durability tests. Furthermore, the EGOR required lower overpotential rather than the oxygen evolution reaction, thus the EGOR coupled with the hydrogen evolution reaction can reduce the cell overpotential to 0.60 V, which is much lower than that of water electrolysis (1.58 V). The effect of Se doping is investigated through experimental analyses and density functional theory (DFT) calculations, and they shows that Se modified the binding energy of Pt nanoparticles and the adsorption energy of reactants by lattice deformation and charge density modification. This study provides scientific insights and strategies for electrocatalyst design for the selective oxidation of polyols to value-added chemicals via the cogeneration of hydrogen gas.

Tumor Growth Kinetics Based on Initial Tumor Volume Doubling Time in Active Surveillance of Low-Risk Papillary Thyroid Carcinoma.

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS.

Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib.

BACKGRUOUND: 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.

Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer.

Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC.

Undercover active surveillance of small highly suspicious thyroid nodules without fine needle aspiration.

PURPOSE: Active surveillance (AS) is an alternative treatment approach for small, low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to assess the clinical outcomes of small, highly suspicious nodules lacking initial cytological confirmation. METHODS: This study included 112 patients with highly suspicious nodules measuring ≤ 10 mm who underwent serial ultrasound at Asan Medical Center, Korea, between 2010 and 2023. RESULTS: The median participant age was 51.9 years, and 74.1% were female. The median maximal tumor diameter and tumor volume (TV) were 4.5 (interquartile range [IQR] 3.7-5.2, range 2.2-9.3) mm and 25.2 (IQR 13.1-49.2) mm3, respectively. During a median follow-up period of 4.8 years, four (3.6%) patients showed a ≥ 3 mm increase in maximal diameter, and two (1.8%) developed new lymph node (LN) metastasis. Disease progression was associated with a TV doubling time (TVDT) of < 5 years and a ≥ 75% increase in TV (p = 0.017 and p < 0.005, respectively). Furthermore, 34.8% of patients underwent fine needle aspiration (FNA), primarily at their own request, yielding 46.2%, 5.1%, 41.0%, and 12.8 % malignant, benign, indeterminate, and non-diagnostic results, respectively. Of 18 patients with PTMC, 8 (44.4%) underwent surgery and 10 continued AS, with no LN metastasis during AS and no postoperative recurrence. CONCLUSION: Small, highly suspicious nodules had a low disease progression rate during AS without FNA. Disease progression was associated with a TVDT of < 5 years and a ≥ 75% increase in TV. FNA can be performed more conservatively than it currently is in patients with highly suspicious nodules measuring ≤ 10 mm.

Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020.

BACKGRUOUND: 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.

Changes in peripheral blood immune cell population in thyroid cancer patients treated with lenvatinib.

This study evaluated changes in the peripheral blood immune cell population in patients with advanced thyroid cancer receiving lenvatinib treatment to confirm the immune-modulatory effect of lenvatinib. After obtaining informed consent from patients, we prospectively collected 20 ml of whole blood at 2-3 months intervals 2-4 times from each patient; peripheral blood mononuclear cells (PBMCs) were separated, and the Maxpar Direct Immune Profiling Assay was performed. A total of 10 patients were enrolled, and 31 blood samples were obtained. The median age of patients was 65 years, and all patients showed durable responses to the lenvatinib treatment. When we compared the PBMC profiles between the pre-treatment, on-treatment, and off-treatment samples, the peripheral natural killer (NK) cell proportion differed significantly. The proportion of NK cells among total live cells significantly increased from 9.3 ± 4.5 (%) in the pre-treatment samples to 20.8 ± 7.9 (%) in the on-treatment samples (P = 0.009) and decreased to 13.3 ± 3.1 (%) in the off-treatment samples (P = 0.07). There was a significant increase in the peripheral NK cell population with lenvatinib treatment in advanced thyroid cancer patients. This finding confirms the immune-modulatory effect of lenvatinib.

Contralateral Low-to-Intermediate Suspicion Nodule Is Not a Contraindication for Lobectomy in Patients with Papillary Thyroid Carcinoma.

Background: The optimal extent of surgery for unilateral papillary thyroid carcinoma (PTC) with contralateral nodules remains unclear. This study evaluated the long-term outcomes in a large cohort of patients with unilateral PTC and contralateral low-to-intermediate suspicious nodules who underwent lobectomy. Methods: This retrospective cohort study included patients with unilateral PTC who underwent lobectomy between January 2016 and December 2017 at Asan Medical Center in Korea. Patients were divided into two groups, those with and without contralateral nodules at the time of lobectomy: the Present group and the Absent group. All contralateral nodules observed at the time of surgery and during follow-up were evaluated. Results: The study cohort consisted of 1761 patients (1879 nodules), including 700 (39.8%) with and 1061 (60.2%) without contralateral nodules. The median size of the contralateral nodules was 0.5 cm. After a median follow-up of 59 months, the median growth of the contralateral nodules in the Present group was 0.1 cm (range, -3.4 to 4.7 cm). Of the contralateral nodules present at the time of lobectomy, 54.7% remained unchanged, decreased in size, or disappeared; whereas 14.8% increased ≥0.3 cm. Of the 700 patients with contralateral nodules, 20 (2.9%) were diagnosed with contralateral PTC. The 5-year contralateral PTC disease-free survival rates in patients with and without contralateral nodules were 98.2% and 99.3% (p = 0.003), respectively, whereas the 5-year recurrence-free survival rates did not differ significantly in these two groups. Of the 39 patients who underwent completion thyroidectomy, 2 (5.1%) experienced permanent hypocalcemia. Conclusions: Lobectomy may be a safe and feasible initial treatment option for patients with unilateral low-risk PTC and contralateral low-to-intermediate suspicious nodules.

Serum thyroglobulin testing after thyroid lobectomy in patients with 1-4 cm papillary thyroid carcinoma.

BACKGROUND: The role of measuring serum thyroglobulin (Tg) levels in patients who have undergone lobectomy has not been proven. The goal of this research is to see if serum Tg levels can predict the recurrence of papillary thyroid carcinoma (PTC) after lobectomy. METHODS: The 463 patients with 1-4 cm PTC who underwent lobectomy between January 2005 and December 2012, were included in this retrospective cohort study. Postoperative serum Tg levels and neck ultrasound were evaluated every 6-12 months after lobectomy during a median 7.8-year follow-up period. The receiver operating characteristic (ROC) curve and its area under the ROC curve (AUC) was used to assess the diagnostic performance of serum Tg levels. RESULTS: During the follow-up, the structural recurrent disease was confirmed in 30 patients (6.5%). The serum Tg levels measured by initial Tg, maximal Tg, and last Tg did not differ statistically between the recurrence and non-recurrence groups. According to our findings, serial patterns of serum maximal Tg variations in 30 patients with recurrence showed no obvious trend and no rising trend toward recurrence before detecting recurrence. The AUC was 54.5% (IQR 43.1%-65.9%) in the ROC curve analysis, indicating that it was not significantly different from the random classifier. CONCLUSION: Serum Tg levels did not differ significantly between the recurrence and non-recurrence groups, and there was no tendency for the recurrence group to increase Tg levels. In patients with PTC who underwent lobectomy, monitoring Tg levels regularly provides little benefit in predicting recurrence.

Inflammatory biomarkers predict outcomes of patients with radioactive iodine refractory thyroid cancer treated with sorafenib.

BACKGROUND: The objective of this multicenter, retrospective cohort study was to evaluate the ability of inflammatory biomarkers representing the host immune system to predict outcomes in 70 patients with progressive radioactive iodine (RAI)-refractory thyroid cancer who were treated with sorafenib. METHOD: Patients were divided into low and high inflammatory biomarker groups based on median values. Progression-free survival (PFS) and overall survival (OS) were assessed based on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). RESULTS: The median LMR, NLR, and PLR values were 3.4, 2.2, and 140.1, respectively. No significant differences were observed in baseline characteristics of high and low LMR, NLR and PLR groups. Median PFS values were 6.6 and 19.5 months in the low and high LMR groups, respectively (P < 0.001). Compared with the high NLR and PLR groups, PFS was significantly prolonged in the low NLR and PLR groups (P = 0.003 and P = 0.041 respectively). In the multivariate analysis, low LMR and high NLR were associated with poor PFS after adjusting for multiple confounding factors including age, sex, pathology, disease-related symptoms, serum thyroglobulin level, lung-only metastasis, cumulative RAI dose, time from diagnosis, and longer diameter of the target lesion (hazard ratio, HR = 2.42; 95% confidence interval, CI 1.25-4.71; P = 0.009, and HR = 2.09; CI, 1.06-4.14; P = 0.033, respectively). High LMR, low NLR, and low PLR were significantly associated with prolonged OS (P = 0.011, P = 0.023, and P = 0.007, respectively). Patients with at least one risk factors for inflammatory biomarkers presented a significantly lower PFS (HR 2.29; CI, 1.36-3.84; P = 0.003) and OS (HR 2.95; CI, 1.49-5.81; P = 0.006) than patients without any risk factor. CONCLUSION: Baseline inflammatory biomarkers successfully predicted PFS and OS in patients with progressive RAI-refractory thyroid cancer treated with sorafenib. These prognostic biomarkers might help arrive at appropriate clinical decisions regarding the use of sorafenib.

Long-term follow-up result of antithyroid drug treatment of Graves' hyperthyroidism in a large cohort.

Objective: This study evaluated the efficacy of antithyroid drugs (ATDs) and risk factors associated with the recurrence of Graves' hyperthyroidism using a comprehensive retrospective cohort. Methods: We included 1829 patients newly diagnosed with Graves' hyperthyroidism, with sufficient follow-up data. Clinical outcomes of the patients and risk factors associated with recurrence-free survival, including the changes in thyrotropin receptor antibody, were evaluated. Results: The median age of the patients was 44.5 years, and 69% were female. Among the patients, 1235 had a chance to withdraw ATD after a median of 23 (interquartile range (IQR) 17.0-35.5) months of treatment. The first remission rate was 55.6% during a median of 72.7 months of follow-up. After the first recurrence, 95% of patients underwent the second course of ATD treatment for a median of 21.1 (IQR 14.8-31.7) months, and the remission rate was 54.1%. During a median of 67 months of follow-up, 7.7% of patients underwent surgery, and 10.5% underwent radioactive iodine therapy. Approximately 30% were still on ATD therapy for recurrent disease or prolonged low-dose maintenance. Younger age (<45 years), male sex, and fluctuating or smoldering of TRAb levels were independent risk factors of the first recurrence after ATD treatment. Conclusions: ATD treatment is an acceptable option for the initial treatment of Graves' hyperthyroidism as well as for recurrent disease. The optimal treatment period for ATD treatment needs to be determined using the individual risk factors of recurrence.

Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study.

Background: Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. Methods: In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. Results: The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group (p = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, p < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively (p < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, p = 0.002) and proteinuria (32%, 18/56 vs. 0%, p < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, p = 0.001) in the sorafenib group. Conclusion: In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.

Limitations of fine-needle aspiration and core needle biopsies in the diagnosis of tall cell variant of papillary thyroid carcinoma.

BACKGROUND: The tall cell variant papillary thyroid carcinoma (TCV-PTC) shows aggressive behaviour. Thus far, the diagnosis of TCV-PTC can only be confirmed using the postoperative specimen. This study aims to evaluate whether fine-needle aspiration (FNA) or core needle biopsy (CNB) could diagnose TCV-PTC preoperatively. METHODS: This is a retrospective cohort study. We included adult patients diagnosed with TCV-PTC or PTC with tall cell features (TCF) at final surgical pathology between January 2015 and December 2018. Preoperative histology was reviewed for six cytomorphologic features suggesting TCV-PTC in FNA or the percentage of tall cells in the CNB specimen. The postoperative pathology was also reviewed to confirm the percentage of tall cells. RESULTS: A total of 119 patients were included in this study; 35 (29%) patients with PTC with TCF served as controls. The most frequent cytomorphological feature in FNA samples of TCV-PTC was tall columnar cells, including single tombstone-like cells (70%). Among 43 TCV-PTC evaluated by FNA, 3 FNA (7%) revealed the absence of any of the six cytomorphologic features suggesting TCV-PTC. When we defined 30% of tall cells in CNB specimens as a cutoff suggesting TCV-PTC, only 16 (41%) TCV-PTCs could be preoperatively detected, and 3 (7%) TCV-PTCs did not have any tall cells. The proportion of tall cells was not associated with the postoperative percentage of tall cells. CONCLUSION: Both cytomorphologic features in FNA and the percentage of tall cells in CNB present limitations for use as accurate preoperative diagnostic tools of TCV-PTC.

Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data.

BACKGRUOUND: 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.

Prognosis of Patients with 1-4 cm Papillary Thyroid Cancer Who Underwent Lobectomy: Focus on Gross Extrathyroidal Extension Invading Only the Strap Muscles.

BACKGROUND: This study was designed to evaluate the prognostic implication of gross extrathyroidal extension (ETE) invading the strap muscles after thyroid lobectomy in patients with 1-4 cm papillary thyroid cancer (PTC). METHODS: This retrospective cohort study included patients with 1-4 cm PTC who underwent thyroid lobectomy from 2005 to 2012. Overall, 595 patients were enrolled after excluding patients with aggressive variants of PTC, gross ETE into a major neck structure, and lateral cervical lymph node (LN) metastasis. We evaluated the risk factors for structural recurrence after lobectomy in 1-4 cm PTC. RESULTS: Seventy-eight patients (13.1%) had gross ETE invading only the strap muscles. During the median follow-up period of 7.7 years, structural recurrence was confirmed in 35 patients (5.9%). The presence of gross ETE was an independent risk factor for structural recurrence (hazard ratio 2.54, 95% confidence interval 1.19-5.44; p = 0.016). Subgroup analysis of patients with gross ETE showed that 11 and 47 patients had low- and intermediate-risk LN metastasis, respectively. A significant difference in recurrence-free survival was observed according to the degree of cervical LN metastasis (p = 0.03). Those without LN metastasis or low-risk LNs had a 75% lower risk of recurrence when compared with those with both gross ETE and intermediate-risk LNs. CONCLUSION: Gross ETE and intermediate-risk cervical LN metastasis were associated with a significantly high risk of recurrence after lobectomy in patients with 1-4 cm PTC. Completion thyroidectomy would be considered in this subgroup of patients but not in all patients with gross ETE invading only the strap muscles.

Graves' disease diagnosed in remnant thyroid after lobectomy for thyroid cancer.

BACKGROUND: The coexistence of Graves' disease with thyroid cancer is well-known and total thyroidectomy is recommended in such cases. However, Graves' disease might be dormant at the time of surgery and diagnosed after lobectomy for thyroid cancer. METHODS: We assessed the incidence and clinicopathological characteristic of newly developed Graves' disease after lobectomy for thyroid cancer between 2010 and 2019. RESULTS: In all, 11043 patients underwent lobectomy for thyroid cancer during the study period, and 26 (0.2%) were diagnosed with Graves' disease during follow-up. The median age was 43.8 years, 88.5% were female, and all were euthyroid before surgery. The median time from lobectomy to the diagnosis of Graves' disease was 3.3 years. Half of the patients were diagnosed based on thyroid function tests during routine follow-up, and others were diagnosed due to symptoms of thyrotoxicosis. Among patients who had checked preoperative thyroid autoantibodies, 61.1% showed positivity. Twenty-one (80.8%), and 2 (7.7%) patients received antithyroid drugs and radioactive iodine therapy, respectively, and 3 (11.5%) underwent completion thyroidectomy. CONCLUSION: Although rare, Graves' disease can occur in the remnant thyroid after lobectomy. Such patients are more likely to have autoantibodies. An appropriate workup is required when hyperthyroidism is found during the follow-up of patients after lobectomy.