Concordance of Molecular Classification Based on Fine Needle Biopsy (FNB) and Surgical Samples

NCT06133374 | Recruiting DMC

• 1 other identifier: HREBA.CC-23-0001
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether results from a fine needle biopsy are the same as results from a larger sample that is acquired from the surgical pathology using the Thyroid GuidePx® test in patients with papillary thyroid carcinoma.

Conditions

Papillary Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Concordance between Thyroid GuidePx® molecular classifications acquired from FNAs and matched frozen surgical samples

  The molecular class assignment (Type 1, Type 2 and Type 3), based on the pattern of expression of prognostic genes, will be compared between samples obtained by FNB and matched frozen surgical specimens. The significance of concordance between the two sample types will be determined using the kappa statistic.

  December 1, 2025

Secondary Outcomes (3)

• The technical success rate in completing a valid Thyroid GuidePx® using FNB and FFPE surgical samples

  December 1, 2025

• The recurrence outcomes using the ATA risk stratification system vs. patients classified by Thyroid GuidePx® using surgical samples

  May 1, 2028

• The test performance of Thyroid GuidePx® as a prognostic test (FNB and surgical samples) in comparison to ATA Risk Stratification.

  May 1, 2028

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with a preoperative tissue diagnosis of PTC (Bethesda VI) or suspicious for PTC (Bethesda V) or a tissue diagnosis of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS) interpreted as Bethesda III or IV cytology (indeterminate nodule) ThyroSpec positive for BRAFV600E, TERT, rearrangements in BRAF, RET, NTRK1, NTRK3, RAS + TERT, RAS + EIF1AX, AKT1, PI3CA, CTNNB1, EGFR, rearrangements in ALK, eligible for partial or total thyroidectomy

You may qualify if:

• Age ≥ 18 years
• A diagnosis of papillary thyroid cancer based on a fine needle biopsy (FNB) interpreted as a Bethesda V or VI cytology
• A diagnosis of Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS) interpreted as Bethesda III or IV cytology (indeterminate nodule) ThyroSpec positive for BRAFV600E, TERT, rearrangements in BRAF, RET, NTRK1, NTRK3, RAS + TERT, RAS + EIF1AX, AKT1, PI3CA, CTNNB1, EGFR, rearrangements in ALK
• Tumor size \> 1 cm in maximal diameter on imaging prior to surgery
• The patient is an operative candidate
• The patient has provided consent

You may not qualify if:

• History of radiation to the neck for situations such as medical radiation, radiation exposure in a work environment (nuclear power plant/reactor), or radiation exposure through release of radioactive materials into the nearby environment from a nuclear power plant/reactor.
• Unable or unwilling to have a fine needle biopsy
• Unwilling to undergo thyroidectomy
• Final pathology does not demonstrate papillary thyroid cancer
• Cases where there is no clear dominant nodule
• Cases where there are multiple nodules that preclude sampling of a defined nodule

Sponsors & Collaborators

• University of Calgary: lead
• Qualisure Diagnostics Inc.: collaborator
• Alberta Health services: collaborator

Study Sites (1)

Foothills Medical Centre

Calgary, Alberta, T2N 1N4, Canada

RECRUITING

Related Publications (25)

• Davies L, Morris LG, Haymart M, Chen AY, Goldenberg D, Morris J, Ogilvie JB, Terris DJ, Netterville J, Wong RJ, Randolph G; AACE Endocrine Surgery Scientific Committee. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER. Endocr Pract. 2015 Jun;21(6):686-96. doi: 10.4158/EP14466.DSCR.

  PMID: 26135963 BACKGROUND

• Sciuto R, Romano L, Rea S, Marandino F, Sperduti I, Maini CL. Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution. Ann Oncol. 2009 Oct;20(10):1728-35. doi: 10.1093/annonc/mdp050.

  PMID: 19773250 BACKGROUND

• Pacini F, Castagna MG. Approach to and treatment of differentiated thyroid carcinoma. Med Clin North Am. 2012 Mar;96(2):369-83. doi: 10.1016/j.mcna.2012.01.002. Epub 2012 Feb 10.

  PMID: 22443981 BACKGROUND

• Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010 Dec;20(12):1341-9. doi: 10.1089/thy.2010.0178. Epub 2010 Oct 29.

  PMID: 21034228 BACKGROUND

• Castagna MG, Maino F, Cipri C, Belardini V, Theodoropoulou A, Cevenini G, Pacini F. Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients. Eur J Endocrinol. 2011 Sep;165(3):441-6. doi: 10.1530/EJE-11-0466. Epub 2011 Jul 12.

  PMID: 21750043 BACKGROUND

• Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.

  PMID: 26462967 BACKGROUND

• Cheng SP, Chien MN, Wang TY, Lee JJ, Lee CC, Liu CL. Reconsideration of tumor size threshold for total thyroidectomy in differentiated thyroid cancer. Surgery. 2018 Sep;164(3):504-510. doi: 10.1016/j.surg.2018.04.019. Epub 2018 May 26.

  PMID: 29843911 BACKGROUND

• Dhir M, McCoy KL, Ohori NP, Adkisson CD, LeBeau SO, Carty SE, Yip L. Correct extent of thyroidectomy is poorly predicted preoperatively by the guidelines of the American Thyroid Association for low and intermediate risk thyroid cancers. Surgery. 2018 Jan;163(1):81-87. doi: 10.1016/j.surg.2017.04.029. Epub 2017 Nov 8.

  PMID: 29128185 BACKGROUND

• Lang BH, Shek TW, Wan KY. The significance of unrecognized histological high-risk features on response to therapy in papillary thyroid carcinoma measuring 1-4 cm: implications for completion thyroidectomy following lobectomy. Clin Endocrinol (Oxf). 2017 Feb;86(2):236-242. doi: 10.1111/cen.13165. Epub 2016 Sep 1.

  PMID: 27467318 BACKGROUND

• Kluijfhout WP, Pasternak JD, Lim J, Kwon JS, Vriens MR, Clark OH, Shen WT, Gosnell JE, Suh I, Duh QY. Frequency of High-Risk Characteristics Requiring Total Thyroidectomy for 1-4 cm Well-Differentiated Thyroid Cancer. Thyroid. 2016 Jun;26(6):820-4. doi: 10.1089/thy.2015.0495. Epub 2016 May 20.

  PMID: 27083216 BACKGROUND

• Murthy SP, Balasubramanian D, Subramaniam N, Nair G, Babu MJC, Rathod PV, Thankappan K, Iyer S, Vijayan SN, Prasad C, Nair V. Prevalence of adverse pathological features in 1 to 4 cm low-risk differentiated thyroid carcinoma. Head Neck. 2018 Jun;40(6):1214-1218. doi: 10.1002/hed.25099. Epub 2018 Feb 8.

  PMID: 29417654 BACKGROUND

• Craig SJ, Bysice AM, Nakoneshny SC, Pasieka JL, Chandarana SP. The Identification of Intraoperative Risk Factors Can Reduce, but Not Exclude, the Need for Completion Thyroidectomy in Low-Risk Papillary Thyroid Cancer Patients. Thyroid. 2020 Feb;30(2):222-228. doi: 10.1089/thy.2019.0274. Epub 2020 Jan 9.

  PMID: 31813323 BACKGROUND

• Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014 Oct 23;159(3):676-90. doi: 10.1016/j.cell.2014.09.050.

  PMID: 25417114 BACKGROUND

• Craig S, Stretch C, Farshidfar F, Sheka D, Alabi N, Siddiqui A, Kopciuk K, Park YJ, Khalil M, Khan F, Harvey A, Bathe OF. A clinically useful and biologically informative genomic classifier for papillary thyroid cancer. Front Endocrinol (Lausanne). 2023 Sep 12;14:1220617. doi: 10.3389/fendo.2023.1220617. eCollection 2023.

  PMID: 37772080 BACKGROUND

• Rubino C, de Vathaire F, Dottorini ME, Hall P, Schvartz C, Couette JE, Dondon MG, Abbas MT, Langlois C, Schlumberger M. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003 Nov 3;89(9):1638-44. doi: 10.1038/sj.bjc.6601319.

  PMID: 14583762 BACKGROUND

• Pitoia F, Jerkovich F, Urciuoli C, Schmidt A, Abelleira E, Bueno F, Cross G, Tuttle RM. Implementing the Modified 2009 American Thyroid Association Risk Stratification System in Thyroid Cancer Patients with Low and Intermediate Risk of Recurrence. Thyroid. 2015 Nov;25(11):1235-42. doi: 10.1089/thy.2015.0121. Epub 2015 Aug 6.

  PMID: 26132983 BACKGROUND

• Zhou H, Mody DR, Smith D, Lloyd MB, Kemppainen J, Houghton J, Wylie D, Szafranska-Schwarzbach AE, Takei H. FNA needle rinses preserved in Cytolyt are acceptable specimen type for mutation testing of thyroid nodules. J Am Soc Cytopathol. 2015 May-Jun;4(3):128-135. doi: 10.1016/j.jasc.2015.01.001. Epub 2015 Jan 9.

  PMID: 31051693 BACKGROUND

• Fuller MY, Mody D, Hull A, Pepper K, Hendrickson H, Olsen R. Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules. Arch Pathol Lab Med. 2018 Feb;142(2):178-183. doi: 10.5858/arpa.2017-0136-OA. Epub 2017 May 24.

  PMID: 28537807 BACKGROUND

• Chen T, Gilfix BM, Rivera J, Sadeghi N, Richardson K, Hier MP, Forest VI, Fishman D, Caglar D, Pusztaszeri M, Mitmaker EJ, Payne RJ. The Role of the ThyroSeq v3 Molecular Test in the Surgical Management of Thyroid Nodules in the Canadian Public Health Care Setting. Thyroid. 2020 Sep;30(9):1280-1287. doi: 10.1089/thy.2019.0539. Epub 2020 May 5.

  PMID: 32242511 BACKGROUND

• Eszlinger M, Bohme K, Ullmann M, Gorke F, Siebolts U, Neumann A, Franzius C, Adam S, Molwitz T, Landvogt C, Amro B, Hach A, Feldmann B, Graf D, Wefer A, Niemann R, Bullmann C, Klaushenke G, Santen R, Tonshoff G, Ivancevic V, Kogler A, Bell E, Lorenz B, Kluge G, Hartenstein C, Ruschenburg I, Paschke R. Evaluation of a Two-Year Routine Application of Molecular Testing of Thyroid Fine-Needle Aspirations Using a Seven-Gene Panel in a Primary Referral Setting in Germany. Thyroid. 2017 Mar;27(3):402-411. doi: 10.1089/thy.2016.0445. Epub 2017 Feb 7.

  PMID: 28071986 BACKGROUND

• Titov S, Demenkov PS, Lukyanov SA, Sergiyko SV, Katanyan GA, Veryaskina YA, Ivanov MK. Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier. J Clin Pathol. 2020 Nov;73(11):722-727. doi: 10.1136/jclinpath-2020-206445. Epub 2020 Mar 25.

  PMID: 32213552 BACKGROUND

• Gonzalez HE, Martinez JR, Vargas-Salas S, Solar A, Veliz L, Cruz F, Arias T, Loyola S, Horvath E, Tala H, Traipe E, Meneses M, Marin L, Wohllk N, Diaz RE, Veliz J, Pineda P, Arroyo P, Mena N, Bracamonte M, Miranda G, Bruce E, Urra S. A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study. Thyroid. 2017 Aug;27(8):1058-1067. doi: 10.1089/thy.2017.0067. Epub 2017 Jul 11.

  PMID: 28521616 BACKGROUND

• Le Pennec S, Konopka T, Gacquer D, Fimereli D, Tarabichi M, Tomas G, Savagner F, Decaussin-Petrucci M, Tresallet C, Andry G, Larsimont D, Detours V, Maenhaut C. Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases. Endocr Relat Cancer. 2015 Apr;22(2):205-16. doi: 10.1530/ERC-14-0351. Epub 2015 Feb 17.

  PMID: 25691441 BACKGROUND

• Kamarudin AN, Cox T, Kolamunnage-Dona R. Time-dependent ROC curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017 Apr 7;17(1):53. doi: 10.1186/s12874-017-0332-6.

  PMID: 28388943 BACKGROUND

• Flack V, Afifi A, Lachenbruch P, Schouten H. Sample size determinations for the two rater kappa statistic. Psychometrika. 1988;53(3):321-5.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

fine needle biopsy sample, frozen tissue

MeSH Terms

Conditions

Thyroid Cancer, Papillary

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Caitlin Yeo, MD

  Alberta Health services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elleine Allapitan

CONTACT

403-220-8440; elleine.allapitan@ucalgary.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2023
• First Posted: November 15, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2028
• Last Updated: January 15, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)