Role of NGS-based ThyroSeq Panel in Cancer Diagnosis in Thyroid Nodules

Thyroid Nodule Clinical Trial

Official title:

Role of NGS-based ThyroSeq Panel in Cancer Diagnosis in Thyroid Nodules

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352766
• Other study ID #: PRO14040164
• Secondary ID: PITT 9006477
• Status: Completed
• Start date: January 2015
• Est. completion date: February 15, 2019

Study information

• Verified date: July 2019
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recently, targeted next generation sequencing (NGS) platforms have been introduced that allow inexpensive testing for hundreds of mutational hotspots at the same time. A number of additional mutational markers in thyroid cancer have been identified. Highly promising markers associated with tumor prognosis have also been found. This multi-institutional study aims to validate the diagnostic use of mutational markers in thyroid nodules with indeterminate cytology.

The proposed hypothesis is that a broad NGS-based genotyping of thyroid nodules using a large panel of mutational markers applied to thyroid FNA samples can provide an accurate cancer risk stratification in thyroid nodules.

The performance of the panel will be tested in a multi-institutional double-blind prospective study of FNA samples from thyroid nodules with indeterminate cytology and available surgical outcome

Description:

Thyroid cancer is the fifth most common cancer type in women and the fastest growing cancer diagnosis in the U.S. In 2013, an estimated 60,000 new cases were diagnosed. However, thyroid nodules are much more common, particularly in woman and with increased age. The prevalence of palpable nodules in population-based studies is 3-4% and the prevalence of non-palpable nodules incidentally identified on imaging approaches 40-50% after the age of 60. Thyroid cancer is the primary clinical concern in patient with thyroid nodules, although only small proportion (~5%) of thyroid nodules is malignant . The diagnosis of thyroid cancer relies on cervical ultrasound and fine needle aspiration (FNA) biopsy with cytologic examination. FNA cytology provides a definitive diagnosis of benign or malignant thyroid disease in most cases, although in approximately 30% of nodules, FNA cytology cannot reliably rule out cancer and such cases are reported as indeterminate for malignancy. Because of the lack of a definitive diagnosis, most patients with indeterminate cytology undergo diagnostic surgery to establish histopathologic diagnosis. However, only 20-30% of such surgically resected thyroid nodules will prove to be malignant. It has been estimated that ~150,000 thyroid surgeries are performed in the U.S. for benign nodules due to inability to rule out cancer without surgery. Additionally, an indeterminate preoperative diagnosis does not always lead to the optimal initial surgical intervention for patients who have thyroid cancer, as many of them undergo a two-step surgery, i.e. thyroid lobectomy followed by completion total thyroidectomy. Both unnecessary and two-step surgeries can be avoided with a more accurate preoperative diagnosis of cancer in thyroid nodules.

For patients who have signed an informed consent, the physician investigator will then perform a research needle wash. The syringe will be rinsed with a buffer solution to gather left over cells for the research sample. This FNA material will be collected for potential molecular testing into a collection tube that is stored at -20C.

The first five samples acquired will be processed irrespective of cytologic diagnosis to evaluate the collection technique.

Those samples that have indeterminate cytologic diagnosis (Bethesda III, VI, or V) and surgical outcome are submitted for molecular testing. (Sample will be given a code that de-identifies the sample before it is sent to the testing laboratory. The lab that will analyze specimens is a CLIA certified Pitt lab.)

Molecular analysis is performed at the Pitt lab without knowing surgical outcome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: February 15, 2019
• Est. primary completion date: February 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients that undergo a clinically diagnostic thyroid FNA

Exclusion Criteria:

• Children

• pregnant women

Related Conditions & MeSH terms

• Thyroid Diseases
• Thyroid Nodule

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (9)

Lead Sponsor	Collaborator
University of Pittsburgh	Duke University, Johns Hopkins University, Ohio State University, University of Cincinnati, University of Colorado, Denver, University of Pennsylvania, University of Wisconsin, Madison, Washington Hospital Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcomes	The primary outcome measured in this study is the performance (sensitivity, specificity, NPV, PPV) of the Thyroseq Panel in diagnosing cancer in thyroid nodules with Bethesda III, VI and V cytology.	April 2016