Plenary 7

21 Mar 2026 16:50 17:30

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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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16:50 17:30	Genomic Alterations in Thyroid Cancer: Biological and Clinical Insights Maria E. CabanillasUnited States Speaker Genomic Alterations in Thyroid Cancer: Biological and Clinical InsightsGenomic alterations play a central role in the initiation, progression, and clinical behavior of thyroid cancers, offering critical insights into their underlying biology and therapeutic vulnerabilities. Follicular cell derived thyroid tumors commonly harbor driver mutations that constitutively activate the MAPK signaling pathway, most notably BRAFV600E and RAS mutations. These early events define major molecular subtypes and strongly influence differentiation status, tumor phenotype, and response to therapy. Progression toward aggressive or dedifferentiated forms, such as poorly differentiated and anaplastic thyroid carcinomas, is driven by additional alterations in key genes regulating chromatin remodeling, cell cycle control, and genomic stability, including TERT promoter mutations, TP53, PIK3CA, and EIF1AX. Actionable genomic alterations are increasingly leveraged to personalize treatment strategies in thyroid cancer and underscore the importance of genomic characterization in improving outcomes in thyroid cancer. Anaplastic Thyroid CancerAnaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, characterized by rapid local invasion, early metastasis, and near‑universal disease‑specific mortality and is considered a medical emergency. Current treatment strategies prioritize rapid assessment of resectability, with surgery pursued only when complete or near‑complete tumor removal is feasible, as partial debulking offers limited benefit. For unresectable disease, localized disease, combined modality therapy—typically external‑beam radiation with concurrent systemic therapy—remains the cornerstone of local control. Recent advances in molecular profiling have transformed systemic management, enabling targeted therapies for tumors harboring BRAFV600E mutations. These agents have demonstrated meaningful responses and, in select cases, have converted unresectable tumors to operable ones, expanding the role of surgery in modern care. However, due to the high risk of relapses, immunotherapy has been added to the treatment strategy. Patients with distant metastatic disease without a BRAFV600E mutation have a more complicated treatment regimen which is still under investigation but require systemic therapy combination strategies involving immunotherapy. These evolving strategies reflect a shift toward precision‑based, time‑critical management aimed at improving outcomes in this highly lethal cancer. 101

Time

Session

16:50

17:30

Genomic Alterations in Thyroid Cancer: Biological and Clinical Insights

Maria E. CabanillasUnited States Speaker Genomic Alterations in Thyroid Cancer: Biological and Clinical InsightsGenomic alterations play a central role in the initiation, progression, and clinical behavior of thyroid cancers, offering critical insights into their underlying biology and therapeutic vulnerabilities. Follicular cell derived thyroid tumors commonly harbor driver mutations that constitutively activate the MAPK signaling pathway, most notably BRAFV600E and RAS mutations. These early events define major molecular subtypes and strongly influence differentiation status, tumor phenotype, and response to therapy. Progression toward aggressive or dedifferentiated forms, such as poorly differentiated and anaplastic thyroid carcinomas, is driven by additional alterations in key genes regulating chromatin remodeling, cell cycle control, and genomic stability, including TERT promoter mutations, TP53, PIK3CA, and EIF1AX. Actionable genomic alterations are increasingly leveraged to personalize treatment strategies in thyroid cancer and underscore the importance of genomic characterization in improving outcomes in thyroid cancer. Anaplastic Thyroid CancerAnaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies, characterized by rapid local invasion, early metastasis, and near‑universal disease‑specific mortality and is considered a medical emergency. Current treatment strategies prioritize rapid assessment of resectability, with surgery pursued only when complete or near‑complete tumor removal is feasible, as partial debulking offers limited benefit. For unresectable disease, localized disease, combined modality therapy—typically external‑beam radiation with concurrent systemic therapy—remains the cornerstone of local control. Recent advances in molecular profiling have transformed systemic management, enabling targeted therapies for tumors harboring BRAFV600E mutations. These agents have demonstrated meaningful responses and, in select cases, have converted unresectable tumors to operable ones, expanding the role of surgery in modern care. However, due to the high risk of relapses, immunotherapy has been added to the treatment strategy. Patients with distant metastatic disease without a BRAFV600E mutation have a more complicated treatment regimen which is still under investigation but require systemic therapy combination strategies involving immunotherapy. These evolving strategies reflect a shift toward precision‑based, time‑critical management aimed at improving outcomes in this highly lethal cancer.

101