medwireNews: A novel genomic sequencing classifier (GSC) can identify cytologically indeterminate thyroid nodules that are benign with a high degree of sensitivity and accuracy, according to a blinded validation study.
Looking at a total of 10,196 genes plus seven other components (including a parathyroid and medullary thyroid cancer cassette), the GSC was able to correctly identify 41 of 45 malignant (Bethesda grade V and VI) thyroid biopsy samples as suspicious, giving a sensitivity of 91.1%. A total of 99 of 145 nonmalignant (Bethesda grade II) samples were correctly identified as benign, providing a specificity of 68.3%.
The study, published in JAMA Surgery, was performed using thyroid nodules collected using fine-needle aspiration biopsy from patients at 49 US centers. Overall, 210 samples had Bethesda grade III/IV indeterminate cytopathology and had been previously used to validate an earlier algorithm, known as the gene expression classifier (GEC). A total of 191 of these samples had enough residual RNA to allow validation of the GSC. Among these Bethesda III/IV samples, the GSC had a negative predictive value of 96.1% and a positive predictive value of 47.1%.
The GEC uses messenger RNA transcript expression levels to categorize cytologically indeterminate nodules as either benign or suspicious, and was previously shown to have a sensitivity and specificity of 90% and 52%, respectively, explain Kepal Patel (New York University Langone Medical Center, USA) and colleagues.
They therefore decided to develop a test that increased the specificity for identifying benign nodules while maintaining high sensitivity for detecting malignancies, feeling that such a test “could spare even more patients from surgery with an accurate benign genomic result […] and increase the cancer yield among those with a suspicious result.”
The GSC fulfills these aims, say the researchers. “In practice, this enhanced performance suggests that among Bethesda III and IV nodules that are histopathologically benign, at least one-third more will receive a benign result using the GSC compared with the GEC,” they write.
Patel et al continue: “This increased benign call rate is expected to result in more patients being assigned to active observation as opposed to diagnostic surgery.”
In an accompanying comment, Peter Angelos, from the University of Chicago in Illinois, USA, writes: “Although the data from this study suggest that genomic sequence classifier testing is an improvement over GEC testing for avoiding surgery for benign nodules, clinicians must be careful in deciding when to use the test.
“If a patient has an indication for surgery other than cytology, then there is little value in pursuing any molecular testing.”
By Catherine Booth
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