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

Overview

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.

Detailed description

Thyroid cancer is the 8th most common cancer, and incidence has been increasing. Papillary thyroid carcinoma (PTC) accounts for most thyroid cancers. Treatment decisions related to PTC depend on the doctor's estimate on whether the cancer is aggressive or not. Current methods for distinguishing aggressive tumors from less aggressive tumors rely on clinical factors as well as factors related to the final pathology (after the tumor has been removed). Ideally, the information required to make decisions would be available prior to surgery, so that surgical decisions can be made.

A new test is being developed to determine molecular features of a PTC and to estimate the risk of cancer recurrence after surgery. Thyroid GuidePx® provides unique information that may inform doctors' decisions. The greatest potential for Thyroid GuidePx® to impact on clinical care is if it can be performed prior to surgery on a fine needle biopsy (FNB). If Thyroid GuidePx® could be done on an FNB, it would inform surgeons on the type of surgery that would be most appropriate for an individual.

A recent feasibility study consisting of 12 patients with PTC demonstrated that performing the Thyroid GuidePx® assay on FNBs is feasible. However, reliance on a limited FNB for molecular disease characterization implies that the sample is representative of the entirety of the tumor. Genomic and transcriptomic heterogeneity has been described in primary tumors and metastases. Therefore, it will be important to document the concordance between samples acquired by FNB and surgical samples. The goal of this study is to determine whether the more limited sample from an FNB is sufficiently representative of the larger tumor to determine a valid molecular classification using the Thyroid GuidePx® test in patients with PTC.

Participants will be invited to participate if they have a preoperative tissue diagnosis of PTC (Bethesda VI) or suspicious for PTC (Bethesda V), and they are eligible for partial or total thyroidectomy. During surgery, when the thyroid gland and the tumor are exposed, the surgeon will perform an FNB of the dominant tumor (ie: the lesion identified preoperatively), under direct vision. The cellular material from the FNB will be sent for processing. Separate surgical samples will be processed and examined. This will follow routine specimen processing protocols and will not interfere with standard methods of pathologic diagnosis. Tissue will be released for research only once sufficient tissue is taken for diagnostic and clinical use. RNASeq for Thyroid GuidePx® for both FNB and surgical samples will be performed and compared.

Primary outcome measures

• Concordance between Thyroid GuidePx® molecular classifications acquired from FNAs and matched frozen surgical samples [Time frame: December 1, 2025]

Secondary outcome measures (3)

• The technical success rate in completing a valid Thyroid GuidePx® using FNB and FFPE surgical samples [Time frame: December 1, 2025]
• The recurrence outcomes using the ATA risk stratification system vs. patients classified by Thyroid GuidePx® using surgical samples [Time frame: May 1, 2028]
• The test performance of Thyroid GuidePx® as a prognostic test (FNB and surgical samples) in comparison to ATA Risk Stratification. [Time frame: May 1, 2028]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• Foothills Medical Centre — Calgary

Publications

• 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
• 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
• 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
• 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. d PMID 21034228
• 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
• 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 Di PMID 26462967
• 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
• 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

Identifiers

NCT: NCT06133374 · HREBA.CC-23-0001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗