BACKGROUND:Serum thyroglobulin (Tg) is a key tumor marker in papillary thyroid carcinoma (PTC), but its reliability may be compromised by the presence of antithyroglobulin antibodies (TgAb). Utilizing the assay-specific limit of quantification (LOQ) may enhance the detection of TgAb-related interference compared with the traditional reference limit. This study evaluated postoperative TgAb levels based on LOQ as a surrogate marker for tumor monitoring in PTC. METHODS:A total of 1039 patients with PTC (≥1 cm) who had undetectable unstimulated serum Tg (<0.2 ng/mL) 6-12 months after total thyroidectomy with radioactive iodine (RAI) ablation therapy (2009-2012) were retrospectively analyzed. Simultaneously measured TgAb levels were classified using both the reference limit (60.0 U/mL) and LOQ (43.4 U/mL) into three groups undetectable (<43.4 U/mL), borderline (43.4-60.0 U/mL), and elevated (>60.0 U/mL). RESULTS:The median age was 48.2 years, and 188 (18.1%) were male. The median tumor size was 1.5 cm, and lymph node metastases were present in 705 patients (67.8%). During a median follow-up of 12.0 years, recurrence occurred in 4.8%. Based on initial TgAb level, patients were classified as undetectable (65.6%), borderline (23.5%), and elevated (10.9%), with corresponding 10-year progression-free survival rates of 97.9%, 94.6%, and 88.5%, respectively (p < 0.001). Multivariable analysis revealed a significantly higher recurrence risk in the borderline group compared with the undetectable group (adjusted hazard ratio, 2.01; confidence interval, 1.03-3.96; p = 0.043). In the borderline group, TgAb became undetectable in 75.0% of patients over 6.3 years, whereas those who remained borderline exhibited a higher recurrence rate of 12.9% (p = 0.01). CONCLUSIONS:TgAb levels above the LOQ were associated with a higher recurrence risk in patients with PTC with undetectable Tg after RAI treatment. Classification of TgAb positivity based on the LOQ may improve prognostic assessment compared with evaluation using conventional reference limits. Further studies are needed to validate our findings and refine TgAb thresholds.

Background Radioactive iodine treatment (RAIT) is an essential therapy for differentiated thyroid cancer. However, unforeseen complications arising during thyroid hormone withdrawal (THW) can lead to Cancellation of the scheduled treatment. This study aimed to identify cases in which THW-RAIT was discontinued due to THW-related complications and to explore potentially preventable causes to improve patient management. Methods Among 4,174 patients who underwent THW-RAIT between 2012 and 2024, 39 did not complete the planned treatment. After excluding Cancellations unrelated to THW, 11 (0.26%) patients with unexpected THW-related medical issues were analyzed. Results The median age of the included patients was 61 years (range, 23 to 70), and 10 were male. The reasons for THW-RAIT Cancellation were hyponatremia (n=1), abnormal liver function (n=1), renal dysfunction (n=3), and combined liver and renal dysfunction (n=6). The patient with hyponatremia was taking a thiazide diuretic. Most cases of liver dysfunction were associated with prior use of herbal medications, whereas renal dysfunction was linked to diuretic or nonsteroidal anti-inflammatory drug use, pre-existing conditions such as single kidney or diabetic nephropathy, or inadequate oral intake during low-iodine preparation. Two cases of concurrent liver and renal dysfunction were attributed to rhabdomyolysis following intense exercise or heavy physical labor. Conclusion Enhanced patient education, comprehensive pre-treatment assessment, and careful avoidance of high-risk medications are essential to prevent THW-related complications and minimize disruptions in RAIT.

BACKGRUOUND:We aimed to investigate the prognostic significance of primary tumor size in patients with pT1-T3a N0 M0 papillary thyroid carcinoma (PTC), minimizing the impact of confounding factors. METHODS:A multicenter retrospective study included 5,759 patients with PTC. Those with lymph node metastasis, gross extrathyroidal extension (ETE), and aggressive variants were excluded. Patients were categorized by primary tumor size (≤1, 1.1-2, 2.1-4, and >4 cm) and subdivided based on the presence of microscopic ETE (mETE). RESULTS:The median age was 48.0 years, and 87.5% were female. The median primary tumor size was 0.7 cm, with mETE identified in 43.7%. The median follow-up was 8.0 years, with an overall recurrent/persistent disease rate of 2.8%. Multivariate analysis identified male sex, larger tumor size, and the presence of mETE as significant prognostic risk factors. The 10-year recurrent/persistent disease rates for tumors ≤1, 1.1-2, 2.1-4, and >4 cm were 2.5%, 4.7%, 11.1%, and 6.0%, respectively. The 2.1-4 cm group had a significantly higher hazard ratio (HR), with the >4 cm group had the highest HR than the ≤1 cm group. Patients with mETE had a higher recurrent/persistent disease rate (4.5%) than those without, with rates by tumor size being 2.6%, 5.6%, 16.7%, and 8.2%. CONCLUSION:Larger tumor size and the presence of mETE significantly increased the risk of recurrent/persistent disease in PTC. Patients with pT2-T3a N0 M0 PTC (>2 cm) had a recurrent/persistent disease risk exceeding 5%, warranting vigilant management.

Background: The necessity of prophylactic central lymph node dissection (p-CLND) in patients with clinically node-negative papillary thyroid carcinoma (PTC) is unclear. The present study evaluated the central lymph node (LN) metastases status in patients with clinically node-negative PTC on both preoperative thyroid ultrasonography (USG) and neck computed tomography (CT) who underwent p-CLND. Methods: This retrospective cohort study included 3002 clinically node-negative patients diagnosed with PTC who had undergone thyroidectomy with p-CLND from January 2000 to September 2022. Clinically node-negative was defined as the absence of suspicious metastatic LNs on preoperative USG and neck CT. Low-risk central LN metastases were defined as LN metastases <2 mm in size with metastatic LNs ≤5. The median follow-up duration was 4.52 (interquartile range [IQR]: 1.6-7.5) years. Results: Of the 3002 patients, 1194 (39.7%) had central LN metastases, whereas 1808 (60.3%) did not. The 1194 patients with central LN metastases included 507 (16.9%) with intermediate-risk metastases and 610 (20.3%) with low-risk LN metastases, with a total of 2428 (80.5%) patients having low-risk LN metastases or no central LN metastases. High-risk metastases were observed in only 77 (2.5%) patients. Of the 584 patients with intermediate-/high-risk metastases, 577 (98.8%) had central LN metastases <1 cm in size, whereas only 7 (1.2%) had central LN metastases ≥1 cm. The disease recurrence rates for the no LN metastases, low-risk LN metastases, and intermediate-/high-risk LN metastases groups were 0.4%, 1.1%, and 1.9%, respectively (p = 0.012). Factors independently associated with intermediate-/high-risk central LN metastases included age <55 years (odds ratio [OR] = 2.29), male sex (OR = 2.33), tumor size >1 cm on USG (OR = 1.94), and the presence of extrathyroidal extension on CT scans (OR = 1.53), with p < 0.001 for all factors. Conclusions: Most LNs confirmed after CLND in cN0 PTC patients assessed by USG and CT were either metastasis-free or classified as low-risk metastatic LNs. Furthermore, the majority of metastatic LNs were small in size, typically measuring <1 cm. p-CLND may be unnecessary if preoperative thyroid USG and neck CT show no evidence of central neck LN metastaes.

PURPOSE:Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence. This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. MATERIALS AND METHODS:This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. RESULTS:We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other's presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. CONCLUSION:Multifocality and bilaterality were not independent risk factors of each other's presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Disclosure: H. Oh: None. M. Jeon: None. C. Kim: None. W. Kim: None. W. Kim: None. J. Ryu: None. T. Kim: None. Background: Radioactive active iodine (RAI) treatment is the essential treatment for advanced differentiated thyroid cancer patient. However, unforeseen complications arising from thyroid hormone withdrawal (THW) can lead to the cancellation of scheduled treatments. We aimed to identify cases of treatment discontinuation during THW-RAI therapy due to THW-related complication and to explore preventable causes for improving patient management. Methods: Between 2012 and 2024, 4,174 patients underwent THW-RAI therapy in Asan Medical Center. Among them, 39 did not complete the planned treatment. After excluding cases canceled for reasons unrelated to THW, 11 patients with unexpected medical issues from THW were analyzed. Results: The median age of the included patients was 65 years (range: 31–72), with 10 being male. The reasons for discontinuation were hyponatremia (1 case), abnormal liver function (1 case), abnormal renal function (3 cases), and concurrent liver and renal dysfunction (6 cases). The patient with hyponatremia had a history of thiazide diuretic use. Most cases of liver dysfunction were associated with prior use of herbal medications, while renal dysfunction was linked to diuretic or non-steroidal anti-inflammatory drug use, pre-existing conditions such as single kidney and diabetic nephropathy, or inadequate oral intake during low-iodine preparation. Notably, two cases of combined liver and renal dysfunction were attributed to rhabdomyolysis following intense exercise or heavy workloads. Conclusions: Our analysis of 11 cases highlights avoidable factors that led to discontinuation of THW-RAI therapy. Enhanced patient education, comprehensive pre-treatment evaluations, and careful avoidance of high-risk medications are critical for minimizing disruptions in RAI therapy. Presentation: Saturday, July 12, 2025

Malignant pleural effusion (MPE) from differentiated thyroid cancer (DTC) is rare and carries a poor prognosis. This study evaluated clinical outcomes and the impact of multikinase inhibitor (MKI) therapy in patients with MPE from DTC. In this retrospective cohort study of 184 DTC patients with lung metastases, 31 (17%) had MPE. After excluding 10 with non-malignant effusion, 174 were analyzed. Patients with MPE were older (P < 0.001) at DTC diagnosis, had higher T stage (P = 0.004), developed pleural metastases earlier (P = 0.016), and had more frequent macro- and polymetastatic lung lesions (P < 0.001) than those without MPE. All MPE cases were radioactive iodine-refractory and developed a median of 6.3 years after DTC diagnosis. Symptomatic MPE occurred in 22 patients (71%), all requiring drainage, while 9 (29%) had asymptomatic MPE. Symptomatic MPE was associated with worse overall survival (OS) compared to patients without MPE (adjusted hazard ratio (HR) 4.62, 95% confidence interval (CI) 2.49-8.57, P < 0.001). Notably, patients initiating MKI therapy for symptomatic MPE had the worst OS (adjusted HR 9.78, 95% CI: 3.52-27.13, P < 0.001). Median OS after MPE diagnosis was 13 months. Symptomatic MPE also had worse post-MPE survival compared to asymptomatic MPE (adjusted HR 5.73, 95% CI: 1.52-21.52, P = 0.009). MKI therapy did not significantly improve OS or progression-free survival after MPE onset. MPE in DTC patients with lung metastases indicates poor prognosis, especially when symptomatic. MKI therapy showed limited survival benefits after MPE onset. Early identification and proactive management of patients at high risk of MPE may improve outcomes.

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.

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 anti- thyroid 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.

Young Joo Park, Eun Kyung Lee, Young Shin Song, Bon Seok Koo, Hyungju Kwon, Keunyoung Kim, Mijin Kim, Bo Hyun Kim, Won Gu Kim, Won Bae Kim, Won Woong Kim, Jung-Han Kim, Hee Kyung Kim, Hee Young Na, Shin Je Moon, Jung-Eun Moon, Sohyun Park, Jun-Ook Park, Ji-In Bang, Kyorim Back, Youngduk Seo, Dong Yeob Shin, Su-Jin Shin, Hwa Young Ahn, So Won Oh, Seung Hoon Woo, Ho-Ryun Won, Chang Hwan Ryu, Jee Hee Yoon, Ka Hee Yi, Min Kyoung Lee, Sang-Woo Lee, Seung Eun Lee, Sihoon Lee, Young Ah Lee, Joon-Hyop Lee, Ji Ye Lee, Jieun Lee, Cho Rok Lee, Dong-Jun Lim, Jae-Yol Lim, Yun Kyung Jeon, Kyong Yeun Jung, Ari Chong, Yun Jae Chung, Chan Kwon Jung, Kwanhoon Jo, Yoon Young Cho, A Ram Hong, Chae Moon Hong, Ho-Cheol Kang, Sun Wook Kim, Woong Youn Chung, Do Joon Park, Dong Gyu Na, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:1-20. https://doi.org/10.11106/ijt.2024.17.1.1

Parathyroid carcinoma is a rare endocrine malignancy for which the primary treatment is surgery; however, 50% of the patients develop local recurrence or distant metastases. No consensus exists on the standard treatment for metastatic parathyroid cancer. Here we report a case of a 41-year-old male with inoperable locally advanced parathyroid carcinoma who was successfully treated with multimodal therapy including radiofrequency ablation (RFA), external beam radiation therapy (EBRT) to the neck, and sorafenib. Eleven months after initiating sorafenib, serum calcium levels were normal, and both the intact PTH level and the size of metastatic lesion remained stable; thus, we decided to discontinue sorafenib. After discontinuation, the disease remained stable for 18 months and continues to be so. Hence, clinicians can consider multimodal treatment with RFA, EBRT, and sorafenib as a treatment option for locally advanced parathyroid carcinoma.

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4) or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4) or newly detected thyroid tumors (n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

CONTEXT:The primary treatment of locoregionally recurrent/persistent papillary thyroid cancer (PTC) is surgical removal by reoperation. However, there had been only limited number of reports on the outcome of reoperation.OBJECTIVE:This study was to evaluate the efficacy of the first reoperation for locoregionally recurrent/persistent papillary thyroid carcinoma and the usefulness of stimulated thyroglobulin for evaluating efficacy of reoperation.DESIGN AND SETTINGS:This was a retrospective observational cohort study in a tertiary referral hospital.PATIENTS:A total of 83 patients, who underwent initial total thyroidectomy and nodal dissection with radioactive iodine remnant ablation, received reoperation for locoregionally recurrent/persistent PTC and were included in this study. Stimulated thyroglobulin levels were assessed before and after reoperation.MAIN OUTCOME MEASURES:We assessed biochemical remission (stimulated thyroglobulin <1 ng/ml) after reoperation and evaluated second clinical recurrence-free survival rate according to stimulated thyroglobulin value.RESULTS:There was a significant positive correlation between the numbers of resected malignant lymph nodes and the reduction in stimulated thyroglobulin level after reoperation. Biochemical remission was achieved in 51% of patients who underwent first reoperation. Patients with stimulated thyroglobulin level greater than 5 ng/ml after first reoperation had a greater chance of a second clinical recurrence (the estimated 5 yr clinical recurrence free survival rate, 94 ± 3 vs.74 ± 9%, log rank statistics 15.8, df = 1, P < 0.001).CONCLUSION:Surgery is an effective option for managing locally recurrent/persistent PTC. Stimulated thyroglobulin is a useful marker for evaluating efficacy of reoperation and predicting second recurrence in locoregionally recurrent/persistent PTC.

The continued advancement of targeted therapies for actionable gene rearrangements has increased the demand for cost-effective screening methods for detecting these gene rearrangements in papillary thyroid carcinoma (PTC). Herein, ribonucleic acid (RNA) sequencing was performed on 106 patients with PTC having wild-type BRAF. The patients were divided into two groups: Group 1 (n = 58) included patients selected by an endocrine pathologist based on characteristic pathological features, including multinodular invasive growth, prominent intratumoral stromal fibrosis, mixed-growth patterns with varying degrees of nuclear atypia, pale eosinophilic to clear cytoplasm, and/or multiple lymph node (LN) metastasis. These patients were prescreened and then subjected to pan-tyrosine receptor kinase (TRK) immunohistochemistry (IHC) staining and RNA sequencing. In Group 2, RNA sequencing was conducted on samples from 48 randomly selected patients. Gene rearrangements were identified in 66 patients (62.3%), with a significantly higher proportion in Group 1 (77.6%) than in Group 2 (43.8%) (p < 0.001). NTRK was the most common gene rearrangement, which was detected in 31 patients (29.2%). The second most common gene rearrangement was RET (18.9%), followed by ALK (9.4%), and then BRAF (2.8%). Patients with gene rearrangements were significantly younger and had smaller primary tumors, although they demonstrated greater extrathyroidal extension and LN metastasis than those without rearrangements. Pan-TRK IHC revealed a sensitivity of 52% and a specificity of 94% for the prediction of NTRK gene rearrangements. This study demonstrates that pathological screening combined with pan-TRK IHC is a cost-effective method for examining targetable gene rearrangements in patients with PTC having wild-type BRAF.

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

Kyong Yeun Jung, Youngduk Seo, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Dong Yeob Shin, Sang-Woo Lee, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:182-7. https://doi.org/10.11106/ijt.2024.17.1.182

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.

Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim, Korean Thyroid Association Guideline Committee on the Managements of Thyroid Nodule and Cancer. Int J Thyroidol 2024;17:168-81. https://doi.org/10.11106/ijt.2024.17.1.168