ETA2024 Poster Presentations Diagnosis of thyroid cancer-1 (10 abstracts)
Appropriately positioned molecular testing for cytologically indeterminate thyroid nodules in an optimized thyroid nodule diagnostic pathway has incremental impact in addition to clinical assessment, cytology and ultrasound malignancy risk
Jiahui Wu 1 , Paul Stewardson 2 , Markus Eszlinger 3 , Moosa Khalil 4 , Sana Ghaznavi 5 , Erik Nohr 6 , Adrian Box 4 & Ralf Paschke 7
1University of Calgary, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, Calgary, Canada; 2University of Calgary, University of Calgary, Department of Medical Science, Calgary, Canada; 3Institute of Pathology, Molecular Pathology, Cumming School of Medicine, Halle (Saale), Germany; 4University of Calgary, Cumming School of Medicine, Department of Pathology and Laboratory Medicine, Calgary, Ab, Canada; 5University of Calgary, Department of Medicine, Section of Endocrinology, Calgary, Canada; 6University of Calgary, Canada; 7Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada
Objective: Molecular test (MT) of cytologically indeterminate thyroid nodules (ITNs) needs to be appropriately focused on clinical situations where it can influence decision making. We therefore evaluated MT as an adjunct to an optimized integrated interdisciplinary thyroid nodule diagnostic pathway.
Methods: 1024 consecutive ITNs were included, each underwent reflexive ThyroSPEC MT between July 30, 2020, and October 30, 2023. A multivariate regression model was built to assess the rates of malignancy (ROM) for ThyroSPEC MT categories and other clinical variables. A nomogram was generated based on the model as a graphical tool to compute the overall ROM in clinical practice.
Results: The model achieved a cross-validated AUC of 0.83. Patients with high-risk mutations or malignant molecular markers exhibited significantly higher odds (152.8 times) of malignancy compared to those with mutation-negative or benign molecular marker results. The ThyroSPEC MT demonstrated a negative predictive value of 92% [CI 84-97%] for ATA low suspicion or TR3 category and 89% [CI 83-94%] for ATA intermediate suspicion or TR4 category. Mutation was the predominant reason for surgery in 55% of patients with intermediate-risk mutations and in 100% of patients with malignant molecular marker and high-risk mutations. 40% of patients opted against surgery despite positive mutation results (64 intermediate-risk mutation, 4 malignant molecular marker or high-risk mutation) due to patient preference based on informed, shared decision-making. However, among patients with a benign mutation, 38% of cases were under surveillance because of the benign mutation, while 19% of cases under surveillance were due to patient preference.
| Covariate | OR (95% CI) | P |
| ThyroSPEC High-risk Mutations or Malignant molecular markers (vs. Mutation Negative or Benign Molecular Marker) | 152.8 (18.8, 1245.0) | <0.0001 |
| ThyroSPEC Intermediate-risk Mutations (vs. Mutation Negative or Benign Molecular Marker) | 5.7 (3.2, 10.1) | <0.0001 |
| Max nodule size >5 (vs. 0-2) | 4.3 (1.6, 11.5) | 0.003 |
| Bethesda Nuclear Atypia (vs. no atypia mentioned) | 4.3 (2.2, 8.3) | <0.0001 |
| USMR 5 (vs. 1-3) | 2.9 (1.3, 6.4) | 0.009 |
| USMR 4 (vs. 1-3) | 1.8 (1.0, 3.4) | 0.063 |
| Palpation Discovery yes (vs. no) | 1.8 (1.1, 3.2) | 0.033 |
| Bethesda BIV (vs. BIII) | 1.6 (0.8, 3.0) | 0.161 |
| USMR 1-3: ATA benign–low risk, ACR-TIRADS 1–3 | ||
| USMR 4: ATA intermediate risk, ACR-TIRADS 4 | ||
| USMR 5: ATA high risk, ACR-TIRADS 5 | ||
Conclusions: High-risk mutations or malignant molecular markers were associated with significantly higher odds of histological malignancy and always impacted clinical management. For the most frequent intermediate-risk mutation nodules, integrating the ROM of the MT results with the ROM of additional clinical variables may further improve clinical decision making. Overall, these results highlight the importance of appropriately positioning and interpreting MTs as an adjunct to an optimized integrated interdisciplinary thyroid nodule diagnostic pathway to further improve diagnostic impact.Model result
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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