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Molecular-Directed Treatment of Differentiated Thyroid Cancer Advances in Diagnosis and Treatment

Linwah Yip, MD1; Julie Ann Sosa, MD, MA2,3,4
[+] Author Affiliations
1Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
2Section of Endocrine Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
3Duke Clinical Research Institute, Durham, North Carolina
4Deputy Editor, JAMA Surgery
JAMA Surg. 2016;151(7):663-670. doi:10.1001/jamasurg.2016.0825.
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Importance  Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer.

Objective  To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer.

Evidence Review  A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only.

Findings  Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer.

Conclusions and Relevance  Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.

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