The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules

Hu, Theodore; Nguyen, Dalena T; Patel, Maitraya; Beckett, Katrina; Douek, Michael; Masamed, Rinat; Rhyu, Jane; Kim, Jiyoon; Tseng, Chi‐Hong; Yeh, Michael W.; Livhits, Masha J.

doi:10.1089/thy.2021.0659

Cited by 18 publications

(10 citation statements)

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“…Sonographic features of the nodule should be considered when evaluating the cost-effectiveness of molecular testing. No significant increase in malignancy rate was demonstrated in ATA ultrasound high suspicion nodules with a positive or suspicious molecular test result with ThyroSeq v3 or Afirma GSC, whereas malignancy rates were increased in ATA ultrasound low-to-intermediate suspicion nodules with a suspicious molecular test result [59 ▪▪ ]. Unlike indeterminate nodules with ATA low-intermediate features on ultrasound, for which molecular testing may add information to better direct management, indeterminate nodules with suspicious sonographic features may be best managed by surgical resection, as molecular testing is unlikely to obviate the need for surgery [59 ▪▪ ,60–62].…”

Section: Ongoing Investigations In Molecular Testingmentioning

confidence: 78%

Molecular testing for indeterminate thyroid nodules: past, present, and future

Raghunathan,

Praw,

Livhits

2023

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of review To examine the origin, current progress, and future directions of molecular testing in indeterminate Bethesda III and Bethesda IV thyroid nodules. Recent findings The diagnostic performance of current genomic tests shows improved benign call rates, specificity and positive-predictive values over prior test versions. The choice of test platform for clinical use should consider test performance, institutional rate of malignancy, nodule cytology and the potential for prognostication to help guide decision-making. Current challenges include test reliability, defining the optimal duration of surveillance, and improving test performance in challenging cytology, such as oncocytic nodules and NIFTP. Opportunities also remain to optimize cost-effectiveness across multiple clinical and practice settings and to refine the use of molecular testing for dynamic risk stratification, such as with BRAF V600E mutation testing. Summary Molecular testing of indeterminate thyroid nodules has helped to reduce the burden of diagnostic surgery, associated healthcare costs, and potential complications. Current-generation tests have demonstrated improvement in diagnostic performance, but challenges remain in improving test performance and refining the scope of testing in care. Decision-making for the management of indeterminate thyroid nodules should consider cytology, clinical and sonographic features, patient values and preferences and molecular testing results, whenever available.

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Section: Ongoing Investigations In Molecular Testingmentioning

confidence: 78%

Molecular testing for indeterminate thyroid nodules: past, present, and future

Raghunathan,

Praw,

Livhits

2023

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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“…Also, a positive molecular test result on a highly suspicious nodule is unlikely to change management. 31 Furthermore, different degrees of suspicion also identify different types of tumours. 9,32 A thyroid nodule with high suspicion sonographic pattern is not only more frequently found to be cancer than a nodule with low suspicion sonographic pattern, but it is also more frequently found to be a papillary thyroid cancer.…”

Section: Institutional Rate Of Malignancy Of Each Category Of Sonogra...mentioning

confidence: 99%

“…Further studies analysing the impact of sonographic pattern on the interpretation and usefulness of molecular tests' results are needed. 31…”

Section: Institutional Rate Of Malignancy Of Each Category Of Sonogra...mentioning

confidence: 99%

“…Such an elevated pretest malignancy rate is likely to render a negative/benign molecular test result unreliable. Also, a positive molecular test result on a highly suspicious nodule is unlikely to change management 31 . Furthermore, different degrees of suspicion also identify different types of tumours 9,32 .…”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

“…Although it seems that there is a higher agreement for diagnostic categories than individual sonographic features, differences in the malignancy rate of each diagnostic category may exist between centres; and therefore, need to be assessed locally before molecular tests are incorporated into the institutional thyroid nodule evaluation pathway. Further studies analysing the impact of sonographic pattern on the interpretation and usefulness of molecular tests' results are needed 31 …”

Section: Molecular Tests For the Evaluation Of Cytologically Indeterm...mentioning

confidence: 99%

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Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

Valderrábano

Eszlinger

Stewardson

et al. 2023

Clinical Endocrinology

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Objective Advances in our understanding of the molecular biology of thyroid tumours is being rapidly translated into their clinical management. This review summarizes the current use of molecular testing in thyroid tumours, focusing on their usefulness as diagnostic and prognostic tools to guide treatment with consideration of present limitations. Design Considerations about molecular testing applications for the diagnosis and treatment of thyroid tumours are divided into four sections/roles: (1) evaluating cytologically indeterminate thyroid nodules; (2) guiding extent of surgery in indeterminate thyroid nodules; (3) completing histological characterization of thyroid tumours and (4) identifying actionable mutations in advanced progressive thyroid cancers. Results Genomic testing can improve the presurgical malignancy risk assessment in indeterminate thyroid nodules. However, a prior in‐depth analysis of institutional quality and outcomes of sonographical, cytological and histological characterization of thyroid tumours is necessary. Presently, it remains uncertain whether knowing the molecular profile of a cytologically indeterminate thyroid nodule might be advantageous to modify the extent of initial surgery. Molecular characterization of thyroid tumours can be a valuable adjunct to morphological diagnosis in some challenging cases, such as in low‐risk follicular cell‐derived neoplasms, or rare tumours. Finally, as selective kinase inhibitors are available, molecular testing in locally advanced/metastatic progressive thyroid cancers should also be integrated into the institutional clinical management pathway to improve outcomes and limit toxicity. Conclusions Molecular testing needs to be implemented into the local evidence‐based clinical management thyroid nodule/cancer pathways to improve its diagnostic and prognostic value and to optimize cost‐effectiveness.

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Risks of malignancy in the major nongynecologic cytopathology reporting systems: Critiques and discussions

Pusztaszeri,

Saieg,

Baloch

2024

Cancer Cytopathology

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The ever‐increasing popularity of standardized systems for reporting cytopathology has led in part to much attention to and importance of the risk stratification schemes, especially the risks of malignancy (ROMs), which are associated with the different diagnostic categories and upon which recommendations for clinical management are based. However, it is well known that the ROM calculations are based on retrospective reviews of the existing literature, representing a heterogeneous patient population, and are plagued by significant biases and variations. Statistically, the ROM represents the post‐test probability of malignancy, which changes with the test result and with the prevalence of malignancy (or pretest probability) in an individual practice setting and individual patient presentation. Therefore, the clinical utility of the ROM is questioned and likely needs a second look in the nongynecologic cytopathology reporting systems. In this communication, the authors discuss the status of the ROM estimates according to the most commonly used nongynecologic reporting systems, including for thyroid, salivary glands, and others, highlighting similarities and differences with a focus on the limitations of ROM estimates and their application in clinical practice.

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The Effect Modification of Ultrasound Risk Classification on Molecular Testing in Predicting the Risk of Malignancy in Cytologically Indeterminate Thyroid Nodules

Cited by 18 publications

References 50 publications

Molecular testing for indeterminate thyroid nodules: past, present, and future

Molecular testing for indeterminate thyroid nodules: past, present, and future

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer

Risks of malignancy in the major nongynecologic cytopathology reporting systems: Critiques and discussions

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