In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

Objectives: . Head and neck squamous cell carcinoma (HNSCC) exhibits high recurrence rates, particularly in cases of radioresistant HNSCC (RR-HNSCC). Non-thermal plasma (NTP) therapy effectively suppresses the progression of HNSCC. However, the therapeutic mechanisms of NTP therapy in treating RR-HNSCC are not well understood. In this study, we explored the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes. Methods: . After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with NTP-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing results, we identified differentially expressed genes (DEGs), followed by a bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC. Results: . NTPAM reduced RR-HNSCC cell viability in vitro. RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species (ROS) pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1,924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes—ABCC3, DUSP16, PDGFB, RAF1, and THBS1—showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as activated markers within 6 hours, and this effect persisted for 12 hours. Furthermore, enrichment analysis indicated that these three DEGs were associated with the extracellular matrix, transforming growth factor-beta, phosphoinositide 3-kinase/protein kinase B, and mesenchymal-epithelial transition factor pathways. Conclusion . NTPAM therapy exerts cytotoxic effects in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing the radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns about overtreatment.For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To support AS implementation, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended to adults with pathologically proven Bethesda V-VI PTMC without clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, or aggressive histology. Baseline assessment requires high‑resolution cervical ultrasound by experienced operators to rule out extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis;contrast‑enhanced neck computed tomography is optional. Patient characteristics such as age, comorbidities, and capacity for long-term follow-up should be assessed. Shared decision-making should weigh the benefits and risks of surgery and AS, expected oncologic outcomes, complications, quality of life, anxiety, medical cost, and patient preference. Follow-up includes cervical ultrasound and thyroid function test every six months for two years, then annually. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline offers a framework to ensure oncologic safety and support patient-centered active surveillance.

Objectives: . The presence of extrathyroidal extension (ETE) in patients with differentiated thyroid cancer (DTC) serves as a significant prognostic indicator. Consequently, the staging of DTC is categorized into extensive ETE and gross ETE that solely impacts the strap muscles (gross strap muscle invasion [gSMI]). However, there is a lack of sufficient evidence concerning the relationship between gSMI and prognosis, particularly in terms of tumor size. Methods: . Relevant literature was searched in Medline, Embase, Cochrane Library, and KoreaMed. All procedures were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and carried out by two independent reviewers. The meta-analysis utilized a random-effects model to account for the diversity of the studies. Risk of Bias for Nonrandomized Studies (RoBANS) version 2.0, an evaluation tool for non-randomized studies, was employed to assess the quality of the selected research. Clinical data from observational studies that examined the relationship between the degree of ETE and prognosis were gathered, and a meta-analysis was conducted. Results: . Eighteen observational studies were included in this analysis. Subgroup analyses were conducted for each outcome. The findings revealed that the recurrence rate (odds ratio [OR], 2.498), disease-specific mortality (risk ratio [RR], 2.984), overall mortality (RR, 1.361), and lymph node (LN) metastasis (OR, 5.355) were significantly higher in patients with gSMI than in those without ETE. However, when the analysis was restricted to tumors measuring 4 cm or smaller, no significant differences in prognostic outcomes were observed, with the exception of LN metastasis. Conclusion . gSMI negatively impacts prognosis; however, this correlation diminishes with smaller tumor sizes. Thus, a more cautious approach is warranted during the treatment process.

Objectives: . The presence of extrathyroidal extension (ETE) in patients with differentiated thyroid cancer (DTC) serves as a significant prognostic indicator. Consequently, the staging of DTC is categorized into extensive ETE and gross ETE that solely impacts the strap muscles (gross strap muscle invasion [gSMI]). However, there is a lack of sufficient evidence concerning the relationship between gSMI and prognosis, particularly in terms of tumor size. Methods: . Relevant literature was searched in Medline, Embase, Cochrane Library, and KoreaMed. All procedures were conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and carried out by two independent reviewers. The meta-analysis utilized a random-effects model to account for the diversity of the studies. Risk of Bias for Nonrandomized Studies (RoBANS) version 2.0, an evaluation tool for non-randomized studies, was employed to assess the quality of the selected research. Clinical data from observational studies that examined the relationship between the degree of ETE and prognosis were gathered, and a meta-analysis was conducted. Results: . Eighteen observational studies were included in this analysis. Subgroup analyses were conducted for each outcome. The findings revealed that the recurrence rate (odds ratio [OR], 2.498), disease-specific mortality (risk ratio [RR], 2.984), overall mortality (RR, 1.361), and lymph node (LN) metastasis (OR, 5.355) were significantly higher in patients with gSMI than in those without ETE. However, when the analysis was restricted to tumors measuring 4 cm or smaller, no significant differences in prognostic outcomes were observed, with the exception of LN metastasis. Conclusion . gSMI negatively impacts prognosis; however, this correlation diminishes with smaller tumor sizes. Thus, a more cautious approach is warranted during the treatment process.

Purpose: The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex. Materials and Methods: This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea. Results: A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits. Conclusion Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

These guidelines aim to establish the standard practice for diagnosing and treating patients with differentiated thyroid cancer (DTC). Based on the Korean Thyroid Association (KTA) Guidelines on DTC management, the “Treatment of Advanced DTC” section was revised in 2024 and has been provided through this chapter. Especially, this chapter covers surgical and nonsurgical treatments for the local (previous surgery site) or regional (cervical lymph node metastasis) recurrences. After drafting the guidelines, it was finalized by collecting opinions from KTA members and related societies. Surgical resection is the preferred treatment for local or regional recurrence of advanced DTC. If surgical resection is not possible, nonsurgical resection treatment under ultrasonography guidance may be considered as an alternative treatment for local or regional recurrence of DTC. Furthermore, if residual lesions are suspected even after surgical resection or respiratory-digestive organ invasion, additional radioactive iodine and external radiation treatments are considered.

Thyroid surgery complications include voice change, vocal fold paralysis, and hypoparathyroidism. The voice status should be evaluated pre- and post-surgery. In patients with voice change, laryngeal visualization is needed.Intraoperative neuromonitoring helps reduce recurrent laryngeal nerve injury. The measurement of serum calcium, parathyroid hormone, and 25-hydroxyvitamin D levels is recommended to evaluate perioperative parathyroid function and prescribe supplementation preoperatively if necessary. For postoperative hypoparathyroidism, vitamin D and oral calcium supplementation are indicated based on serum parathyroid hormone and calcium levels and the severity of symptoms or signs of hypocalcemia. If long-term treatment is required, the appropriateness of treatment should be evaluated based on the disease itself and the consideration of potential benefits and harms from long-term replacement.