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10:30
12:00
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Preoperative Thyroid Nodule Diagnosis
Chia-Hung LinTaiwan
Moderator
Novel Biomarkers and Treatment Strategies in Thyroid Eye DiseaseThyroid Eye Disease (TED), also known as Graves' orbitopathy, remains a complex autoimmune condition that significantly impacts patients' vision and quality of life. Traditionally, management has relied mainly on non-specific anti-inflammatory therapies. However, as our understanding of its molecular pathogenesis evolves, there is an increasing clinical demand for more precise diagnostic tools and targeted therapeutic interventions.
This presentation provides a comprehensive overview of the current landscape and future directions in the management of TED. We will discuss the emergence of novel serum and molecular biomarkers that offer potential for earlier diagnosis and more accurate prediction of disease progression. These biomarkers may bridge the gap between clinical observation and underlying immunological activity. Furthermore, we will explore the shift in treatment paradigms, moving from conventional systemic corticosteroids toward innovative biological agents. By targeting specific signaling pathways involved in orbital inflammation and remodeling, these new strategies aim to provide more effective and durable clinical outcomes.
The integration of novel biomarkers and advanced treatment modalities is reshaping the management of TED. Moving toward a more individualized approach will allow clinicians to optimize therapeutic timing and selection, ultimately improving the long-term prognosis for patients with this challenging condition.
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Guodong FuCanada
Speaker
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.
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Samantha Peiling YangSingapore
Speaker
Harnessing Molecular Diagnostics in Cytologically-Indeterminate Thyroid NodulesRe-Differentiation Therapy in RAI-Refractory Thyroid Cancer
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13:50
15:20
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Thyroid Eye Disease Management
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Chia-Hung LinTaiwan
Speaker
Novel Biomarkers and Treatment Strategies in Thyroid Eye DiseaseThyroid Eye Disease (TED), also known as Graves' orbitopathy, remains a complex autoimmune condition that significantly impacts patients' vision and quality of life. Traditionally, management has relied mainly on non-specific anti-inflammatory therapies. However, as our understanding of its molecular pathogenesis evolves, there is an increasing clinical demand for more precise diagnostic tools and targeted therapeutic interventions.
This presentation provides a comprehensive overview of the current landscape and future directions in the management of TED. We will discuss the emergence of novel serum and molecular biomarkers that offer potential for earlier diagnosis and more accurate prediction of disease progression. These biomarkers may bridge the gap between clinical observation and underlying immunological activity. Furthermore, we will explore the shift in treatment paradigms, moving from conventional systemic corticosteroids toward innovative biological agents. By targeting specific signaling pathways involved in orbital inflammation and remodeling, these new strategies aim to provide more effective and durable clinical outcomes.
The integration of novel biomarkers and advanced treatment modalities is reshaping the management of TED. Moving toward a more individualized approach will allow clinicians to optimize therapeutic timing and selection, ultimately improving the long-term prognosis for patients with this challenging condition.
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Ichiro YamauchiJapan
Speaker
Management of Thyroid Eye Disease: Insights from Clinical Experience and MRI Findings in JapanIn Japan, disease activity of thyroid eye disease (TED) is commonly assessed using magnetic resonance imaging (MRI) in addition to clinical activity score (CAS). Recently, we proposed an MRI-guided categorization of active moderate-to-severe TED based on our retrospective data.
We retrospectively analyzed TED cases treated at our department between 2015 and 2022 with a combination of daily steroid pulse therapy and orbital radiation. Among 44 cases with diplopia, we classified 17 cases as severe (diplopia in the primary position) and 27 as non-severe (diplopia only in non-primary positions). The severe group was older (median 67 years) and had lower TSAb titers (median 324%) compared to the non-severe group (median 56 years, median TSAb 2443%). CAS was similar between the groups. MRI revealed that proptosis was more pronounced in the non-severe group (median 21.4 mm) than in the severe group (median 17.5 mm), whereas the difference in proptosis between eyes was larger in the severe group (median 2.0 mm) than in the non-severe group (median 0.9 mm). High signal intensity of orbital fat on STIR sequence was more frequently observed in the non-severe group (68.2%) than in the severe group (20.0%).
These findings suggest that TED patients with severe diplopia are characterized by older age, lower TSAb titers, and greater asymmetry in proptosis. In contrast, CAS and STIR signal intensity of orbital fat were not indicative of severity. In this context, severe diplopia often develops despite low CAS and mild proptosis.
We also present our clinical experience with teprotumumab, an anti–IGF-1 receptor antibody. Since its launch in Japan in 2024, we have treated several patients with severe TED, the majority of whom showed remarkable improvement in clinical features. However, adverse effects such as hearing impairment and hyperglycemia were occasionally observed, highlighting the importance of appropriate management.
In conclusion, MRI-guided evaluation provides valuable insights for individualized management of TED. Evidence regarding the efficacy of teprotumumab remains limited in the subtype characterized by severe diplopia, which often presents with low CAS and mild proptosis. The MRI-guided approach may help clinicians select optimal therapeutic strategies, including steroid pulse therapy, teprotumumab, and other emerging agents.
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Kelvin ChongHong Kong, China
Speaker
Update on Thyroid Eye Disease Management - Asia Pacific PerspectivesExisting guidelines/recommendations/consensus on the management of thyroid eye disease (TED)/Graves' orbitopathy (GO) pose significant difficulties when applied in the Asia Pacific region. The presenter will share his experiences and challenges in setting up the first thyroid eye clinic in Hong Kong, developing an image-guided medical and surgical decompression, while looking into the future of intelligence-based management of TED/GO.
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