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Original Investigation |

Effect of Gene Expression Classifier Molecular Testing on the Surgical Decision-Making Process for Patients With Thyroid Nodules

Salem I. Noureldine, MD1; Matthew T. Olson, MD2; Nishant Agrawal, MD1; Jason D. Prescott, MD, PhD3; Martha A. Zeiger, MD3; Ralph P. Tufano, MD, MBA1
[+] Author Affiliations
1Division of Head and Neck Endocrine Surgery, Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
2Division of Cytopathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
3Endocrine Surgery, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA Otolaryngol Head Neck Surg. 2015;141(12):1082-1088. doi:10.1001/jamaoto.2015.2708.
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Importance  Commercial molecular testing, such as the gene expression classifier (GEC), is now being used in the work up of cytologically indeterminate thyroid nodules. While this test may be helpful in ruling out malignancy in a thyroid nodule, its effect on surgical decision making has yet to be fully defined.

Objective  We aimed to determine the effect and outcome of GEC test results on the decision-making process for patients with thyroid nodules presenting for surgical consultation.

Design, Setting, and Participants  A surgical management algorithm was developed that incorporated individual Bethesda System for Reporting Thyroid Cytopathology classifications, in addition to clinical, laboratory, and radiological findings. We then retrospectively applied this algorithm to 273 consecutive patients with thyroid nodules and GEC test results who had presented for surgical consultation between February 1, 2012, and December 31, 2014.

Interventions  GEC testing.

Main Outcomes and Measures  Changes in management were recorded to identify the effect of GEC testing on the surgical decision-making process. An alteration in management of 20% of cases was considered significant.

Results  Of the 273 consecutive patients assessed by the GEC, mean (SD) age was 50.8 (14.7) years, 204 (74.7%) were female, and the mean (SD) nodule size was 2.4 (1.3) cm. Test results were suspicious for 233 (85.3%); benign for 31 (11.4%); and indeterminate for 8 (2.9%). The GEC test was also positive for medullary thyroid cancer for 1 patient (0.4%). The GEC test was correctly used as a rule-out test in only 127 patients (46.5%) with indeterminate nodules who lacked a clinical indication for surgery. The clinical management plan of only 23 (8.4%) patients was altered as a result of GEC test results, and of these 23 patients who proceeded to surgery, 16 patients (72.7%) were found to be inappropriately overtreated relative to postoperative histopathology analysis. We found that GEC testing did not affect the surgical decision-making process in 250 (91.6%) of our patients. In 146 cases, the use of GEC testing was not clinically indicated, and the test was being overused in patients for whom the results would not change surgical management. The positive predictive value of the GEC test for cytologically indeterminate nodules was 42.1%, and the negative predictive value was 83.3%.

Conclusions and Relevance  The GEC testing did not significantly affect the surgical decision-making process. Gene expression classifier testing is often used incorrectly and is overused in patients for whom the results would not change management. The GEC test demonstrated a lower than expected negative predictive value, and there was evidence of overtreatment among patients whose treatment was altered based on this test.

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Management Algorithm for Patients Presenting With Nodular Thyroid Disease

Symptoms included hoarseness, dysphagia, discomfort, pain, pressure, and/or difficulty breathing. If preoperative suspicious lymph nodes were identified, total thyroidectomy with therapeutic central compartment neck dissection would be performed.

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Use of GEC in the General Population
Posted on December 27, 2015
Prerak Shah, MD, FACS
New England ENT & Facial Plastic Surgery, Clinical Instructor, Harvard Medical School
Conflict of Interest: None Declared
Thank you for sharing your experience with use of the GEC in your patient population. With the increased scrutiny and demand for accountability with the health care dollar and with the overuse, and often misuse, of this technology, these types of reviews are going to become more and more important to help standardize our approach. As mentioned in your article, there does seem to be a referral bias with your patient population resulting in your higher rate of malignancy in Bethesda III patients (38%) compared to historical norms (5-10%) and with the rate of GEC suspicious results in category III/IV(87%/88%) compared to Alexander, et al, study from the NEJM (57%/60%). The presumable lack of referrals for GEC benign and cytopathologically low risk nodules would impact the number of patients who were spared surgery and may not fully represent the true value of GEC if used in a general population (with a likely higher NPV and lower incidence of malignancy). I think larger scale studies in the future will hopefully help determine if the GEC should be instituted as an appropriate and cost-effective strategy for Bethesda III/IV patients in general rather than from a tertiary thyroid referral center. Given a large patient study group in its entirety, the GEC could have positively impacted your surgical decision-making process in a cost-effective manner - I am not sure if we know that answer at this time. In addition, I think it was important to highlight that a suspicious GEC result should not routinely impact the decision-making process for extent of surgery in light of its poor specificity. Thanks again for sharing this data.
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