Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier.

Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III-VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9-100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1-100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.

Disparities in the initial presentation of differentiated thyroid cancer in a large public hospital and adjoining university teaching hospital.

BACKGROUND: Healthcare disparities associated with insurance and socioeconomic status have been well characterized for several malignancies, such as lung cancer. To assess whether there are healthcare disparities in thyroid cancer, this study evaluated the stage on initial presentation of patients with differentiated thyroid cancer (DTC) in a public versus university teaching hospital. METHODS: A retrospective chart review was performed to identify patients with a new diagnosis of DTC from January 1, 2007, to January 1, 2010, in a large public and adjoining university teaching hospital at a single academic medical center. Medical records were reviewed for demographics, pathology, and American Joint Committee on Cancer tumor-node-metastasis stage at initial presentation. RESULTS: There were 49 cases of well-DTC (96% papillary and 4% Hürthle) in the public hospital and 370 cases (95% papillary, 2% Hürthle, and 3% follicular) in the university teaching hospital. Median age (years) at presentation was 50 in the public versus 48 in the university teaching hospital (p=0.39). Ninety-six percent of public hospital patients were from ethnic minorities compared with 16% of university teaching hospital patients (p<0.0001). Only 1 (2%) public hospital patient had private insurance compared with 85% of university teaching hospital patients. Tumor status (p=0.002) and stage (p=0.03) were more advanced and extrathyroidal extension (p=0.02) was more prevalent among public hospital patients compared with university teaching hospital patients. In a multivariable analysis, public hospital, male gender, increasing age, advanced tumor status, and the presence of lymphovascular invasion were the best predictors of more advanced disease stage. Public hospital patients were 3.4 times more likely to present with advanced DTC than university teaching hospital patients of the same age, gender, tumor status, and lymphovascular invasion status (95% confidence interval 1.29-8.95). CONCLUSIONS: In a public hospital, where the patient population is defined primarily by insurance status, patients were more likely to present with advanced-stage DTC than patients presenting to an adjacent university teaching hospital. These results suggest a disparity in the stage on initial presentation of DTC, possibly resulting in a delayed diagnosis of cancer.