Clinical trial NCT06133374: Concordance of Molecular Classification Based on Fine Needle Biopsy (FNB) and Surgical Samples
Official title: Concordance of Molecular Classification Based on Fine Needle Biopsy (FNB) and Surgical Samples
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Papillary Thyroid Cancer
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Qualisure Diagnostics Inc.
name: Alberta Health services
First posted: 2023-11-15
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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.

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

Primary outcomes:
measure: Concordance between Thyroid GuidePx® molecular classifications acquired from FNAs and matched frozen surgical samples
timeFrame: December 1, 2025
Secondary outcomes:
measure: The technical success rate in completing a valid Thyroid GuidePx® using FNB and FFPE surgical samples
timeFrame: December 1, 2025
measure: The recurrence outcomes using the ATA risk stratification system vs. patients classified by Thyroid GuidePx® using surgical samples
timeFrame: May 1, 2028
measure: The test performance of Thyroid GuidePx® as a prognostic test (FNB and surgical samples) in comparison to ATA Risk Stratification.
timeFrame: May 1, 2028
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
Study officials:
affiliation: Alberta Health services
name: Caitlin Yeo, MD
role: PRINCIPAL_INVESTIGATOR
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