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Endocrinology these patients’ nodules are malignant after an indeterminate biopsy has often required surgery. “Previously, the standard of care for determining if these nodules were cancerous was to remove the half of the thyroid with the suspicious nodule,” Dr. Harari says. “If pathology showed that it was cancer, the patient returned to the operating room within 10 days of surgery to remove the other side of the thyroid. Thus, patients who turn out to have cancer are subjected to two surgeries instead of one. That also unfortunately means that at least 70 percent of patients would end up having surgery for benign nodules.” That’s where molecular proﬁling comes in. The UCLA team has been using an analysis test that they have validated through their own use with patients. The analysis uses a so-called gene- expression classifier to determine whether a nodule is benign. “In about half of the cases where we have indeterminate cytology, the test will come back with a benign result, which means the likelihood of cancer is only 4 percent — the same likelihood as when the original biopsy comes back benign,” Dr. Yeh says. “That means these patients can avoid surgery.” If the gene-expression classiﬁer comes back as suspicious, which it does in about half of the patients, the risk of cancer is roughly 40 percent, and those patients are recommended for surgery. While the test is useful for its negative predictive value — determining which suspicious nodules are benign — a second test currently under study by the UCLA team is more useful for its ability to declare malignancies. The test looks for markers from among 17 mutations associated with cancer. When the test is positive, it is nearly 90-percent likely that the nodule is malignant and the patient should have a total thyroidectomy. Again, in such cases the patient is spared an initial diagnostic surgery. Now, Dr. Yeh says, the challenge is to determine how to optimally use the two types of molecular- proﬁling tests to maximize value for patients with indeterminate ﬁne-needle-aspiration biopsy results. As they continue to actively monitor how the molecular-proﬁling tests perform, Dr. Yeh and colleagues are looking into ways to better sort the patients with indeterminate cytology by risk. Ideally, the initial test would be used for the lower- risk patients and the second positive-marker test would be used for higher-risk patients. The airway (white semicircle with black in the middle) is to the left in this scan, with the cancer (gray with white dots plus a halo of mostly blue-colored blood ﬂow) in the center, and the carotid artery (multi-colored circle) on the right. “Unfortunately, we have no perfect test yet,” Dr. Yeh says. “We have some that are more sensitive and some that are more speciﬁc. In an ideal world there would be no such thing as diagnostic surgery — no patient would ever have to go through two operations, and no patient would have an unnecessary operation. We may never quite get there, but we can get closer.” To learn more about endocrine surgery at UCLA, go to: endocrinesurgery.ucla.edu “When a biopsy reveals a benign result ... we follow up with serial imaging and biopsy again later if sonographic changes are detected within the nodule. On the other end of the spectrum, when the biopsy gives a diagnosis of cancer, patients are treated with one definitive surgery.” — Avital Harari, MD 5 UCLA Physicians Update