Molecular Classifier for the Fine Needle-based Assessment of Malignancy Risk in Thyroid Nodules (ThyroPred-1)

Prospective Validation of the Molecular Classifier for the Fine Needle-based Assessment of Malignancy Risk in Thyroid Nodules

This study evaluates the usefulness of molecular classifier to aid the diagnosis of malignancy in the material obtained by fine-needle aspiration biopsy (FNAB) of thyroid nodule. All participants will undergo FNAB with routine cytological assessment and molecular testing. Patients will undergo surgery or be followed-up, according to the clinical guidelines. The diagnostic power of combined molecular/clinical classifier will be compared to prediction based on clinical features only, by investigators blinded to the final diagnosis of surgical assessment.

Study Overview

• Status: Completed
• Conditions: Thyroid Cancer; Thyroid Nodule; Thyroid Neoplasm

Detailed Description

Currently, the diagnosis of malignancy of thyroid nodule is based on cytological assessment of fine-needle aspiration biopsy (FNAB) classified according to the Bethesda System for Reporting of Thyroid Cytopathology. This does not allow for the definitive diagnosis of cancer in significant proportion of tumors, so called indeterminate nodules (Bethesda class III, IV and V). These patients require surgery to establish a definitive diagnosis, leading to unnecessary operating procedures in at least 2/3 of subjects.

Molecular classifiers could significantly improve thyroid preoperative diagnostics, although they are not optimal and provide either high specificity to the detriment of low sensitivity or conversely, relatively low specificity with high sensitivity. The classifiers could be based on gene expression or mutations present in FNAB specimen.

In the present study the investigators plan to assess the improvement of classification power by molecular gene-expression-based multi-feature classifier when added to standard clinical parameters indicating the risk of malignancy (Bethesda class, tumor size, patient age and sex). Participants will undergo FNAB with prospective collection of material for molecular testing and simultaneous preoperative recording of all clinical parameters. The patients will be operated on or followed-up according to the clinical guidelines. The comparison of a predictive power of clinical criteria to the combined clinical-molecular classifier will be carried out by the group of investigators blinded to the results of final surgery.

• Study Type: Observational
• Enrollment (Actual): 599

Contacts and Locations

Study Locations

• Poland
  • Gliwice, Poland, 44-101
    • Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (above 18 years old) diagnosed with a thyroid nodule, in whom the fine-needle aspiration biopsy is undertaken to establish the necessity of thyroid surgery

Description

Inclusion Criteria:

• a diagnosis of thyroid nodule
• considerable chance for surgical procedure following biopsy result
• patient's consent for collection of material during routine fine needle aspiration biopsy

Exclusion Criteria:

• age below 18 years
• the presence of contraindications that make surgical treatment impossible
• prior diagnosis of thyroid cancer
• antithrombotic treatment except of acetylsalicylic acid or low molecular weight heparin at a prophylactic dose

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy in patients with indeterminate FNAB results who undergone surgery within 6 months from biopsy	The improvement in accuracy of classification will be compared between sole clinical criteria (Bethesda class, tumor size, age, and sex) and combined classifier built on both clinical parameters and gene expression data. The population of indeterminate nodules will be defined by expert analysis of cytological samples by pathologists blinded to the outcome of surgery. Diagnostic accuracy will defined as the percentage of patients who were correctly diagnosed as benign or malignant based on the data available preoperatively.	until surgery or 6 months from biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy in all patients recruited to the study, who were operated on or remained in follow-up for at least 24 months from biopsy.	The improvement in accuracy of classification will be compared between sole clinical criteria (Bethesda class, tumor size, age, and sex) and combined classifier built on both clinical parameters and gene expression data. All patients after surgery will be included. Tumors in patients not operated on will be considered benign after confirmation of stable tumor status at least with 24 months follow-up. Patients not operated on and with shorter follow-up will be excluded.	until surgery or 24 months from biopsy

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Investigators: Study Chair: Barbara Jarzab, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology; Study Director: Rafal Tarnawski, MD, PhD, Maria Sklodowska-Curie National Research Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 3, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Indeterminate thyroid nodule; Thyroid nodule; Molecular biopsy; Gene expression classifier
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Thyroid Nodule
• Other Study ID Numbers: 267398/4/NCBR/2015/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No