| Time | Session |
|---|---|
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10:30
11:00
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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.
102
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11:00
11:30
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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.
102
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11:30
12:00
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102
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