Diagnostic and prognostic value of a 7-panel mutation testing in thyroid nodules with indeterminate cytology: the SWEETMAC study

Bardet, Stéphane; Goardon, Nicolas; Lequesne, Justine; Vaur, Dominique; Ciappuccini, Renaud; Leconte, Alexandra; Monpeyssen, Hervé; Saguet-Rysanek, Virginie; Clarisse, Bénédicte; Lasne-Cardon, Audrey; Ménégaux, Fabrice; Leenhardt, Laurence; Buffet, C

doi:10.1007/s12020-020-02411-4

Cited by 14 publications

(8 citation statements)

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“…In a European setting, with relatively limited costs for surgery and hospital admission, cost-effectiveness of these commercial molecular tests seems unattainable [7]. Locally developed and less comprehensive European molecular panels are available, but their diagnostic accuracy appears too limited for routine application in daily practice [35][36][37]. Due to large global variations in local healthcare expenses, case-mix, and availability of techniques, cost-utility, and convenience of any diagnostic workup will greatly vary among different healthcare systems [7,25,38,39].…”

Section: Discussionmentioning

confidence: 99%

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

Koster

Geus‐Oei

Brouwers

et al. 2022

Eur J Nucl Med Mol Imaging

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Purpose To assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32–53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68–93%]) in the diagnostic surgery group (p < 0.001). [18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28–53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33–63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2–40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively. Conclusion An [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. Trial registration number This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.

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Section: Discussionmentioning

confidence: 99%

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

Koster

Geus‐Oei

Brouwers

et al. 2022

Eur J Nucl Med Mol Imaging

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“… 3 , 4 Strong-driver, BRAF V600E-like mutations, are highly predictive of malignancy but occur in extremely low frequency in benign nodules. 5 , 6 Weak-driver, RAS -like mutations are common but much less predictive of malignancy. 7 , 8 Additional epigenomic factors, including miRNAs, likely contribute to the ultimate phenotype.…”

Section: Introductionmentioning

confidence: 99%

A Retrospective Evaluation of the Diagnostic Performance of an Interdependent Pairwise MicroRNA Expression Analysis with a Mutation Panel in Indeterminate Thyroid Nodules

Finkelstein

Sistrunk

Malchoff

et al. 2022

Thyroid

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Background: The addition of genetic analysis to the evaluation of thyroid nodule fine-needle aspiration biopsy samples improves diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs) with Bethesda III or IV cytopathology. We previously reported the performance of a multiplatform molecular test, referred to in this study as MPTXv1, that includes a mutation panel (ThyGeNEXT ® ) plus an algorithmic microRNA (miRNA) risk classifier (ThyraMIR ® ). Complex interactions of growth-promoting and -suppressing miRNAs affect the phenotype. We previously demonstrated that accounting for these interactions with pairwise miRNA expression analysis improves the diagnosis of medullary thyroid carcinoma. In this study, we assess the impact of pairwise miRNA expression analysis on risk stratification of ITNs. Methods: Pairwise expression analysis of 11 miRNAs was performed on a training cohort of histopathology-proven benign nodules ( n = 50) to define the mean and standard deviation of each pairwise analysis and create a Benign/Malignant Profiler (MPTXv2), deviations from which predicted the malignancy risk. Clinical validation of MPTXv2 was assessed using a cohort of 178 ITN (Bethesda III and IV) samples from a multicentered, blinded retrospective study, previously evaluated by MPTXv1. Results: Compared with MPTXv1, MPTXv2 significantly improved the test performance. The receiver operating characteristic (ROC) areas under the curve (AUC) increased from 0.85 to 0.97 ( p < 0.001), and the diagnostic accuracy at the positive threshold increased significantly ( p < 0.05) from 83% [95% confidence interval (CI) = 76–88] to 93% [CI = 89–96]. The significant improvement in the ROC AUC and the diagnostic accuracy was due to a strong statistical trend for improvement in specificity at the positive threshold. At the positive threshold, the specificity for MPTXv1 was 90% [CI = 84–95] and improved to 98% [CI = 94–99] for MPTXv2. Using the MPTXv2, the Moderate-Risk cohort decreased from 50 samples (28% of the cohort) to 24 samples (13% of the cohort). This 52% decrease is statistically significant ( p < 0.001) and clinically meaningful. Conclusion: As compared with MPTXv1, pairwise miRNA expression analysis used in MPTXv2 significantly improved the diagnostic accuracy of ITN risk stratification and reduced the size of the Moderate-Risk group. Prospective trials are indicated to confirm these findings in a clinical practice setting.

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“…В некоторых случаях после лобэктомии обнаруживают злокачественный процесс, и объем операции расширяется -выполняется тиреоидэктомия [7]. Проведение избыточных по объему и повторных оперативных вмешательств сопряжено с риском возникновения осложнений, а также со значительными экономическими затратами [8]. Таким образом, необходима более точная предоперационная оценка риска развития злокачественного процесса с целью выработки оптимальной хирургической тактики.…”

Section: Introductionunclassified

Diagnostic and prognostic significance of detecting mutations in the <i>BRAF, TERT, RAS, RET/PTC, PAX8/PPARG</i> in the material of fine needle aspiration biopsy thyroid nodules in the IV cytological group (Bethesda, 2017)

Musaelyan

Лапин

Назаров

et al. 2022

Opuholi golovy i šei

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Introduction. Fine needle aspiration biopsy followed by cytological examination is the gold standard in the diagnosis of thyroid nodules. However, up to one third of cases represent an indeterminate result (Bethesda Thyroid Classification, 2017) III—V). Among such cases, category IV is the most common and most difficult to interpret (Bethesda, 2017). The study objective is to determination of the diagnostic and prognostic significance of the molecular genetic study of the fine needle aspiration biopsy material in patients with thyroid nodules with the cytological category Bethesda, IV.Materials and methods. The study included surgical thyroid samples obtained from patients whose cytological examination revealed pathology of cytological category IV according to the Bethesda classification (2017). group 1 included surgical samples from 143 patients with thyroid lesions, and group 2 - cytological material from 45 patients. Determination of the BRAF V600E mutation, mutations in the RAS genes (KRAS, HRAS, NRAS) was carried out using allele-specific polymerase chain reaction, and the RET / PTC1, RET / PTC3 and PAX8 / PPARG translocations were determined using reverse transcription polymerase chain reaction. Sanger sequencing was used to detect mutations in the promoter region of the TERT gene.Results. In group 1, an overall prevalence of the studied mutations in thyroid cancer was 35.1 %: 8.8 % of cases were mutation BRAF V600E, 24.6 % - mutations in the RAS genes, 1.8 % - mutation C228T in the TERT gene. The C228T mutation in the TERT gene was found in 1 case of widely invasive Hurtle cell carcinoma. The prevalence of mutations in benign formations was 4.7 %. mutations in RAS genes were also found in them in group 1, mutation BRAF V600E was associated with the presence of extrathyroid invasion (p = 0.024), vascular invasion (p = 0.018), and lymph node metastases (p = 0.018). In group 2, using the genetic panel sensitivity and specificity were equal: 36.4 and 93.9 %, respectively. positive and negative predictive values were 66.7 and 81.6 %, respectively. No RET / PTC and PAX8 / PPARG translocations were found in groups 1 and 2.Conclusion. The investigated molecular genetic panel, having a high specificity for carcinomas, will make it possible to supplement the cytological diagnostics of material in the category Bethesda, IV. BRAF V600E was associated with an aggressive morphological pattern.

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Diagnostic and prognostic value of a 7-panel mutation testing in thyroid nodules with indeterminate cytology: the SWEETMAC study

Cited by 14 publications

References 38 publications

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial

A Retrospective Evaluation of the Diagnostic Performance of an Interdependent Pairwise MicroRNA Expression Analysis with a Mutation Panel in Indeterminate Thyroid Nodules

Diagnostic and prognostic significance of detecting mutations in the <i>BRAF, TERT, RAS, RET/PTC, PAX8/PPARG</i> in the material of fine needle aspiration biopsy thyroid nodules in the IV cytological group (Bethesda, 2017)

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