SIX YEAR CLINICAL AND IMAGING FOLLOW UP OF AN OFFICE BASED GENE EXPRESSION CLASSIFIERUSED TO MANAGE THYROID NODULES

Transcription

1 SIX YEAR CLINICAL AND IMAGING FOLLOW UP OF AN OFFICE BASED GENE EXPRESSION CLASSIFIERUSED TO MANAGE THYROID NODULES

2 Investigator B Michael MD FACE ECNU Gettysburg PA

3 Disclosures Speakers Bureau Veracyte Corp Genzyme Corp

4 The Blind Men and The Elephant

5 The Blind Men and the Elephant by John Godfrey Saxe ( ) It was eight men of Indostan To learning much inclined, Who went to see the Elephant (Though all of them were blind), That each by observation Might satisfy his mind So oft in Hippocratic wars, The disputants, I ween, Rail on in utter ignorance Of what the other means, And prate about an Elephant Not one of them has seen

6 The Thyroid Cancer Parable

7 The Thyroid Cancer Challenge In the early days of thyroidology, 5% of thyroid nodules turned out to be malignant and without sophisticated testing, most pts went to surgery to rule out cancer 1 In the mid-80 s FNA reduced the number of diagnostic surgeries by about 50%, by identifying patients with benign cytology Today, however, 10-30% of thyroid FNA s are pre-classified by cytologists as indeterminate (not clearly benign or malignant), and in this group only 25% are malignant on surgical path (so that 75% of surgeries in this group could be avoided at a cost of $12-15,000 per surgery) 2,3 1 Mazzaferri EL NEJM Bryson et al Arch O Matolaryngol Head Neck Surg Li H, et al J Clin Endocrinol Metab 2011

8 Molecular Diagnostics in Thyroidology 60% of thyroid cancers appear to contain at least one known genetic mutation Molecular analysis has an evolving role as an adjunct to cytologic analysis of FNA material Several commercial products are now available to evaluate thyroid aspirates using genetic technologies

9 Veracyte/Afirma A commercially available gene expression classifier is approved for clinical use with indeterminate FNA specimens In three validation studies, the Afirma/GEC has demonstrated high sensitivity and high negative predictive value while helping physicians decide which patients with indeterminate FNA s should undergo Tx

10 METHODS The collection period constituted the first 26 months that the Afirma/GEC technique was commercially available

11 Study Structure 447 individual thyroid nodules were evaluated in adult patients between January 2011 and March 2014 in my location All nodules were >1 cm in size All material was submitted for liquid based cytology or alcohol fixation cytology to the same thyroid cytopathology group Preserved RNA was submitted for Afirma/GEC analysis on all indeterminate specimens (Veracyte in San Francisco)

12 44 GEC were successfully run on 44 patients with indeterminate cytology. 28 GEC suspicious specimens were referred for surgery

13 The compiled short term results of a larger multi city sample have been reported elsewhere. 16 GEC benign nodule patients were evaluated for long term follow up from the Gettysburg location This is the subject group of the study

14 Limited long term follow up data are available regarding patients evaluated in this manner I am reporting the 6 year outcomes data from the patients in a single location

15 Study Design Patients with benign Afirma/GEC markers were observed with interval history, physical exam and ultrasound at 6 months from initial biopsy, then annually thereafter with exceptions for symptoms or cosmesis)

16 RESULTS Three of the GEC benign Group underwent surgery within the first year of observation (18%) One had a large symptomatic nodule with benign histopathology One had rapid symptomatic enlargement of a nodule during pregnancy. (benign histopathology)

17 RESULTS One had two GEC evaluated nodules with one reported benign and the second suspicious. The classifier was correct in each case on final pathology

18 This raises the obvious questions What could possibly go wrong? Does utilizing this expensive test really save money in the long run?

19 RESULTS The remaining thirteen GEC benign patients(82%) were successfully followed by the criteria discussed. 6 have been followed 5-6 years 4 have been followed years 3 have been followed years

20 RESULTS All patients in this group have remained asymptomatic Physical exam has remained stable Serial ultrasound examination has shown no change in appearance, volume or characteristics of the nodules under surveillance

21 CONCLUSIONS Literature suggests 10-30% of thyroid nodules biopsied and submitted for cytology are not clearly benign or malignantcytologically indeterminate Initial results in pooled group reported previously 17.8 % Gettysburg subset 10%

22 CONCLUSIONS 37 percent of patients in this indeterminate group who previously would have been referred for surgery have been observed using Afirma/GEC results for guidance

23 CONCLUSIONS Long term Follow up of GEC benign thyroid nodules in a community practice setting for a time period of up to six years appears to be a viable option to surgery in many patients with indeterminate cytology on initial biopsy

24 CONCLUSIONS Potential savings to the medical system in this small sample are estimated at $91,000 using average medicare reimbursement for thyroid surgery in South Central PA plus facility fees and deducting the cost of genetic testing

25 UNANSWERED ISSUES What is the Afirma/GEC false negative rate in clinical practice? My numbers of operated benign Afirma/GEC s are too small at this point to be meaningful If a substantial number of GEC benign indeterminate patients can be safely followed over long time periods without adverse outcome does the above issue matter?

26 In the future, larger numbers of GEC benign patients who undergo surgery for other reasons will likely provide a real world answer to this question I am preparing the data from the initial collection dates onward and hope to report these larger patient numbers as well

27 IN 2017 Clinical judgment using all the historic and diagnostic data still trumps any one test As the arbiter of who gets surgery and who doesn t, the endocrinologist remains the blind-man-in-chief.

28 The unexamined life is not worth living SOCRATES ( B.C.E.)

29 The unexamined practice is not worth paying CMS (1965-? )

30 SPECIAL THANKS RM Harrell MD FACP FACE ECNU Memorial Center for Integrative Endocrine Surgery, Hollywood FL (previous) Kathleen Hands MD FACE ECNU Thyroid Diagnostic Center of S. Texas San Antonio TX (previous)

31 THANK YOU