[Symposium] Thyroid (3)
21 Mar 2026
08:30
10:00
201BC
New Development in Thyroid Cancer Management
Guodong FuCanada
Moderator
Preoperative Molecular Testing for Thyroid NodulesTitle: Preoperative Quantitative Molecular Testing for a Definitive Cancer Diagnosis among Patients with Thyroid Nodules
Objective: Molecular testing is increasingly used in the assessment of thyroid nodules. Tumors harboring the same genomic variant may not behave the same because a gene variant is not expressed equally in tumor cells among patients. This study is to delineate interpatient variabilities in genomic variants in thyroid tumors and assess their diagnostic significance in definitive thyroid cancer diagnosis.
Methods: Interpatient differences in BRAF V600E, TERT promoter, and RAS variants (ie, NRAS, HRAS, and KRAS) were analyzed in residual thyroid fine-needle aspiration (FNA) biopsies and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated.
Results: This retrospective study enrolled 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years), including 438 surgically resected thyroid tumors and 249 thyroid nodule FNA biopsies. Of 438 tumors, 178 (40.6%) and 58 (13.2%) carcinomas were detected with interpatient variabilities of BRAF V600E and TERT promoter variants (C228T and C250T), with variant allele fraction (VAF) levels ranging from 0.03% to 48.56% and 0.13% to 54.74%, respectively. Furthermore, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS, with VAF levels ranging from 0.15% to 51.53%. VAF assays of 249 residual FNA specimens identified 50 specimens (20.1%) with BRAF V600E, 25 FNAs (10.0%) with TERT promoter variants, and 36 specimens (14.5%) with RAS variants with interpatient variabilities (including 23 FNAs [9.2%] with NRAS, 10 FNAs [4.0%] with HRAS, and 3 FNAs [1.2%] with KRAS). Interpatient differences in the 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were detected in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 ND FNAs (23.7%). Compared with the 5 gene variants detected in the matched surgical specimens, VAF assays on residual FNA biopsies exhibited a high agreement (κ = 0.80; P < .001) and demonstrated a sensitivity of 87.1% (95% CI, 69.2%-95.8%), specificity of 92.5% (95% CI, 78.5%-98.0%), PPV of 90.0% (95% CI, 72.3%-97.4%), and NPV of 90.2% (95% CI, 75.9%-96.8%).
Conclusions: This diagnostic study delineated that quantitative discrimination of interpatient variabilities in genomic variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.
Won Gu KimSouth Korea
Moderator
Advances in the Treatment of Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Multikinase Inhibitors and Beyond – An Asian PerspectiveDifferentiated thyroid cancer (DTC) arising from follicular cells generally has a good prognosis; however, about 5-10% of patients experience recurrence or distant metastasis. High-dose radioactive iodine (RAI) therapy is the mainstay of treatment for metastatic DTC, but its efficacy depends on the iodine avidity of the tumor. Iodine uptake of metastatic lesions tends to decline over time, and ultimately, around 60-70% of metastatic cases become refractory to RAI therapy. Patients whose metastases remain RAI-avid have a median survival approaching 10 years, whereas those with RAI-refractory disease have a roughly 10% of 10 10-year survival. Because the clinical course of RAI-refractory DTC is variable, it is critical to determine which patients should receive systemic therapy with a tyrosine kinase inhibitor (TKI) and how to integrate local treatment before and during systemic therapy.
TKIs such as sorafenib and lenvatinib, which primarily inhibit tumor angiogenesis, have been approved. The DECISION trial reported that sorafenib achieved a median progression-free survival (PFS) of 10.8 months compared with 5.8 months in the control group. The SELECT trial showed that lenvatinib achieved a median PFS of 18.3 months versus 3.6 months in controls. Based on these results, sorafenib and lenvatnib are now widely used as the first-line treatments for patients with RAI-refractory DTC who have progressive or symptomatic metastatic disease. A recent multi-center real-world study in Korea suggested that lenvatinib provides better efficacy and longer PFS (median 35.3 months) than sorafenib (median 13.3 months, p<0.001). However, lenvatinib is also associated with higher rates of adverse events such as hypertension (95%) and proteinuria (80%). These TKIs show activity irrespective of the underlying genetic alterations that drive thyroid cancer.
Recently, selective NTRK and RET inhibitors have been developed for solid tumors harboring NTRK or RET gene fusions, and their efficacy has been confirmed in clinical trials. In addition, genetic testing to identify actionable mutations is increasingly being incorporated into practice, and personalized treatment approaches are reflected in current clinical guidelines. A recent Korean multicenter study found that approximately 31% of patients with RAI-refractory thyroid cancer who had wild-type BRAF carried targetable gene fusions. The choice and sequencing of TKI, the optimal timing of their use, strategies to prevent and manage adverse events, and individualized treatment plans based on patient characteristics will be crucial for improving clinical outcomes in patients with RAI-refractory thyroid cancer.
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08:30
09:00
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Chih-Yuan WangTaiwan
Speaker
Obesity 2026 updateObesity remains one of the most critical and rapidly evolving global health challenges entering 2026, characterized by persistently rising prevalence, expanding clinical consequences, and profound societal and economic impacts. Over the past three decades, the prevalence of overweight and obesity has more than doubled among adults and increased nearly threefold among children and adolescents worldwide, driven by complex interactions between genetic susceptibility, obesogenic environments, sedentary lifestyles, dietary transitions toward energy-dense ultra-processed foods, and broader socio-economic determinants. Projections indicate that, if current trends continue, more than half of the global adult population and a substantial proportion of children will be living with obesity within the next two decades, with particularly rapid increases occurring in low- and middle-income countries undergoing nutritional and urban transitions. This epidemiologic shift has translated into a marked escalation in obesity-related non-communicable diseases, including type 2 diabetes, cardiovascular disease, chronic kidney disease, non-alcoholic fatty liver disease, osteoarthritis, and several obesity-associated malignancies, positioning excess adiposity as a leading contributor to global morbidity, mortality, and disability-adjusted life years. Alongside the growing disease burden, the conceptual framework of obesity has undergone important refinement. While body mass index remains a pragmatic population-level screening tool, its limitations in capturing adiposity distribution and metabolic risk have prompted international efforts to redefine obesity as a chronic, relapsing disease characterized by excess or dysfunctional adipose tissue with heterogeneous clinical expression. Emerging diagnostic paradigms increasingly emphasize waist-based measures, ectopic fat accumulation, and the presence of obesity-related complications, distinguishing pre-clinical obesity from clinically manifest disease and enabling more precise risk stratification and individualized management. Therapeutically, the obesity landscape has been transformed by advances in incretin-based pharmacotherapy, particularly glucagon-like peptide-1 receptor agonists and dual or multi-agonist agents, which have demonstrated unprecedented and sustained weight reduction alongside meaningful improvements in cardiometabolic outcomes. The recent development of effective oral formulations further expands treatment accessibility and has the potential to improve long-term adherence, although challenges related to cost, equity, and health-system implementation remain substantial. Importantly, pharmacotherapy alone is insufficient to address the obesity epidemic, and contemporary management strategies emphasize multimodal, life-course approaches integrating nutritional therapy, physical activity promotion, behavioral and psychological interventions, digital health technologies, and, when appropriate, metabolic and bariatric surgery, tailored to individual risk profiles and comorbidity burdens. At the population level, global policy initiatives increasingly recognize that obesity is not solely an individual responsibility but a systems-driven condition requiring coordinated action across healthcare, education, food systems, urban planning, and regulatory environments to create supportive contexts for healthy living. Concurrently, ongoing research continues to elucidate the complex pathophysiology of obesity, including the roles of genetics, epigenetics, gut microbiota, neuroendocrine regulation, and adipose tissue inflammation, while implementation science seeks to bridge gaps between evidence and real-world practice. Collectively, the 2026 obesity update portrays a paradoxical landscape of escalating global burden alongside unprecedented scientific and therapeutic progress, underscoring that meaningful and sustainable impact will depend on integrating biomedical innovation with structural policy reform, equitable access to care, and sustained public health commitment to reverse current trajectories and improve outcomes across the lifespan.Long-Term Changes of Urinary Exosomal Peptide Levels after Thyroidectomy in Patients with Thyroid Cancer: A Prospective Observational StudyIn this prospective observational study, we investigated whether longitudinal changes in urinary exosomal peptide profiles after thyroidectomy could predict recurrence risk in patients with papillary thyroid cancer, a disease with reported recurrence rates of up to 30%. Adults older than 20 years with newly diagnosed papillary thyroid cancer who had undergone thyroidectomy were enrolled, and urine samples were collected at 12 months after study entry and again one year later for exosomal peptide identification and comparison. Seventy patients were included and stratified according to the interval between surgery and enrollment (<5 years, 5–10 years, and >10 years). During the two-year follow-up after enrollment, no recurrences were observed. Across groups and time intervals, there were no significant differences in serum protein levels or urinary exosomal peptide concentrations, and established high-risk clinical factors showed only weak correlations with these biomarkers. Collectively, these findings delineate the long-term basal fluctuation ranges of serum proteins and urinary exosomal peptides in post-thyroidectomy thyroid cancer survivors, suggesting that biomarker levels remaining within these ranges may be indicative of a lower long-term risk of recurrence in high-risk patients following thyroidectomy.
201BC
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09:00
09:30
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Chen-Kai ChouTaiwan
Speaker
Salvage Radiofrequency Ablation Followed by External Beam Radiotherapy for Inoperable Recurrent Differentiated Thyroid Cancer
201BC
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09:30
10:00
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Samantha Peiling YangSingapore
Speaker
Harnessing Molecular Diagnostics in Cytologically-Indeterminate Thyroid NodulesCytologically indeterminate thyroid nodules (Bethesda III–IV) remain a common diagnostic challenge, as cytology alone cannot reliably distinguish benign from malignant disease. Molecular diagnostic tests have emerged as important adjuncts to refine malignancy risk and guide clinical management. This presentation reviews the molecular landscape of thyroid cancer relevant to indeterminate nodules, including key somatic alterations such as BRAF, RAS, and gene fusions (e.g., RET, NTRK, ALK), and discusses the performance of contemporary molecular diagnostic tests. Data from North America and emerging real-world experience in Singapore will be highlighted. The clinical utility of molecular diagnostics in reducing unnecessary diagnostic surgery and informing the extent of surgical management will be discussed, together with current guidance from the ATA 2025 guidelines on integrating molecular results with clinical, radiologic, and cytopathologic findings. Re-Differentiation Therapy in RAI-Refractory Thyroid CancerRadioactive iodine (RAI) therapy remains a cornerstone in the management of differentiated thyroid cancer. However, a subset of patients develop RAI-refractory disease due to loss of iodine-handling gene expression, including the sodium–iodide symporter (NIS). This loss is frequently associated with activation of the MAPK signalling pathway driven by oncogenic alterations such as BRAF and RAS mutations. While systemic therapy with multi-targeted or mutation-specific tyrosine kinase inhibitors (TKIs) can control disease progression, these treatments are generally not curative and do not consistently restore RAI sensitivity.
Re-differentiation therapy has emerged as a promising strategy to restore iodine uptake by targeting MAPK signalling and re-inducing thyroid-specific gene expression. This presentation will review the biological rationale for re-differentiation therapy and summarize key clinical studies evaluating BRAF and MEK inhibition in patients with RAI-refractory thyroid cancer. Emerging approaches, optimal treatment duration, and potential predictors of response will also be discussed, highlighting the potential of re-differentiation therapy to restore the therapeutic benefit of RAI in selected patients.
201BC
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