Malignancy Predictors, Bethesda and TI-RADS Scores Correlated With Final Histopathology in Thyroid Diseases

Correlation of Malignancy Predictors, Bethesda (I-VI) and TI-RADS Scores (I-V) With Final Histopathology in Patients Undergoing Total Thyroidectomy 34 Years After Chernobyl Disaster: Multi-centric Trial

In the last decades, thyroid cancer incidence has continuously increased all over the world, almost exclusively due to a sharp rise in the incidence of the papillary histologic subtype, which has the highest incidence of multifocality. Furthermore, Black Sea and Eastern European regions are both endemic and known to have been under the influence of Chernobyl nuclear explosion. Although overscreening might have a role in certain parts of the world, the predictors of malignancy such as family history, genetical disorders, previous radiation exposure, low iodine intake, diabetes and obesity, should also be taken into consideration in determining the extent of surgery.

Study Overview

• Status: Unknown
• Conditions: Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroid Carcinoma; Thyroid Nodule; Aspiration; Thyroid Goiter; Thyroid Papillary Carcinoma; Multinodular Goiter, Adolescent; Solitary Thyroid Nodule; Multifocal Dysplasia
• Intervention / Treatment: Procedure: Total thyroidectomy (TT)

Detailed Description

High-frequency ultrasound (US) is increasingly used to help distinguish malignancy in patients with solitary or multiple nodules, and US-guided fine needle aspiration (FNA) has become the gold standard test for detecting thyroid cancer. Moreover, a further US-based risk stratification of thyroid nodules with Thyroid Imaging Reporting and Data System (TI-RADS) has been currently proposed for better and easier decision making. However, the presence of multiple nodules in the thyroid gland may decrease the diagnostic value of these preoperative diagnostic tools. The prevalence of incidental carcinoma identified on the final histological examination of the patients who underwent surgery for presumably benign thyroid diseases was previously reported to be roughly around 5 to 10%. Most of the previous studies also showed a lower risk of carcinoma in multinodular goitre (MNG) compared to solitary thyroid nodule (STN). However, some recent surgical series have reported that the risk of thyroid carcinoma in benign thyroid diseases is significantly higher than previously reported.

The purpose of the present study is to detect the accuracy of preoperative cytology and US-findings (TI-RADS) and the prevalence of thyroid carcinoma in patients operated for thyroid diseases and to discuss all malignancy risk factors in detail along with final histopathological report. Cytology-histology discrepant cases will also be further evaluated for sampling and interpretation errors, and possible solutions to increase the accuracy of preop testing are going to be proposed. The accuracy of the preference of total thyroidectomy procedure will be evaluated considering the prevalence of incidental carcinomas diagnosed postoperatively, and whether there are variations in the risk of malignancy with respect to final pathology of patients will also be discussed in detail.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34764
    • Umraniye Education and Research Hospital, Health Sciences Universit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with benign or malign thyroid disease, eligable for total thyroidectomy

Description

Inclusion Criteria:

• >17 years all patients with benign/malign thyroid disease, total thyroidectomy is indicated/preferred by both primary surgeon and patient (signed informed consent is a must)
• All patients should have a malignancy predictive factors forms filled in
• All patients should have fine needle aspiration cytology (Bethesda category) available
• All patients should have an ultrasound evaluated according to TI-RADS
• All patients should have a final histopathology report

Exclusion Criteria:

• Patients who are prepared for thyroid surgery other than total thyroidectomy procedure
• Age<17 years

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Total Thyroidectomy (TT)-indicated patients; Patients with presumably benign thyroid disease (multinodular goitre, solitary thyroid nodule, toxic goitre, etc.) Patients with thyroid carcinoma (biopsy-proved) Total thyroidectomy preference by the primary surgeon	Procedure: Total thyroidectomy (TT); Final total thyroidectomy histopathology report should be available for correlations with preoperatively determined malignancy predictive factors, Bethesda (cytology) and TI-RADS (ultrasound findings)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative Evaluation of Malignancy Risk Factors-How many risk factors are present?	Malignancy risk factors: 1. Demographics (Age and gender-Male/Female), 2. Smoking history (Yes/No, duration and number/day), 3. Iodine-deficient diet (Yes/No), 4. Born at an endemic area (Yes/No), 5. Presence in an endemic area (Yes/No), 6. Radiation exposure (Yes/No), 7. Radiation treatment during childhood (Yes/No), 8. Head and neck carcinoma (Yes/No), 9. Other carcinoma history (Yes/No, if yes specify.........) 10. Family history of thyroid disease (Yes/No), 11. Family history of other carcinomas (Yes/No), 12. Personal history of thyroid carcinoma/surgery (Yes/No, if yes, pathology……..), 13. Personal history of other carcinomas (e.g. colonic polyps? breast disease?......) 14. Genetic disorders (Yes/No), 15. Obesity (Body mass index - ? kg/m2), 16. Diabetes mellitus (Yes/No) should be evaluated for each patient before surgery- The number of risk factors will be compared with malignancy rate found at final histopathology report.	12 months
Preoperative Bethesda category, Fine needle aspiration (FNA) cytology report	Bethesda score-FNA cytology report- as I, II, III, IV, V or VI. Cytology report will be compared with final histology report for each patient for malşgnancy rate and multifocality I. Nondiagnostic or unsatisfactory, II. Benign, III. Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS), IV. Follicular neoplasm or suspicious for a follicular neoplasm-Preoperative cytology category will be compared with postoperative final histopathology report for malignancy rate, multifocality and cases with cytology-histopathology discrepancy will be evaluated further for biopsy techniques and cytology mis-interpretations. V. Suspicious for malignancy, VI. Malignant.	12 months
Preoperative ultrasound evaluation with Thyroid Imaging Reporting and Data System (TI-RADS)	TI-RADS score-Ultrasound evaluation of thyroid nodues- as I, II, III, IV or V. TI-RADS scores will be compared with final histopathology report to see malignancy rates and accuracy of TI-RADS. TI-RADS 1: Normal thyroid gland. No focal lesion. TI-RADS 2: Benign nodules. Noticeably benign pattern (0% risk of malignancy) TI-RADS 3: Probably benign nodules (<5% risk of malignancy) TI-RADS 4: 4a - Undetermined nodules (5-10% risk of malignancy) Score of 1.; 4b - Suspicious nodules (10-50% risk of malignancy) Score of 2.; 4c - Highly suspicious nodules (50-85% risk of malignancy) Score of 3-4 TI-RADS 5: Probably malignant nodules (>85% risk of malignancy) Score of 5 or higher TI-RADS 6: Biopsy-proven malignancy	12 months
Total thyroidectomy for both benign and malign thyroid diseases	Final histopathology report-After surgery (all patients should have a final histopathology report after total thyroidectomy operation). Final histology report will be correlated to Malignancy risk factors (number), Bethesda category (accuracy, false negativity/positivity) and TI-RADS (accuracy, false negativity/positivity)	12 months

Collaborators and Investigators

• Sponsor: Umraniye Education and Research Hospital
• Investigators: Study Chair: Ethem UNAL, MD, PhD, Assoc. Professor of General Surgery and Surgical Oncology

Publications and helpful links

General Publications

• Delfim RLC, Veiga LCGD, Vidal APA, Lopes FPPL, Vaisman M, Teixeira PFDS. Likelihood of malignancy in thyroid nodules according to a proposed Thyroid Imaging Reporting and Data System (TI-RADS) classification merging suspicious and benign ultrasound features. Arch Endocrinol Metab. 2017 May-Jun;61(3):211-221. doi: 10.1590/2359-3997000000262. Epub 2017 Mar 27.
• Tufano RP, Noureldine SI, Angelos P. Incidental thyroid nodules and thyroid cancer: considerations before determining management. JAMA Otolaryngol Head Neck Surg. 2015 Jun;141(6):566-72. doi: 10.1001/jamaoto.2015.0647.
• Tan H, Li Z, Li N, Qian J, Fan F, Zhong H, Feng J, Xu H, Li Z. Thyroid imaging reporting and data system combined with Bethesda classification in qualitative thyroid nodule diagnosis. Medicine (Baltimore). 2019 Dec;98(50):e18320. doi: 10.1097/MD.0000000000018320.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 27, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: International; Radiation; Cytology; Endemic; Total Thyroidectomy; Multi-centric; Black Sea; Eastern Europe; Fine needle aspiration (FNA); Multifocality; Bethesda; Thyroid Imaging Reporting and Data System (TI-RADS); Multicentric study
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Adenocarcinoma, Papillary; Carcinoma; Thyroid Diseases; Thyroid Neoplasms; Thyroid Cancer, Papillary; Goiter; Thyroid Nodule; Carcinoma, Papillary
• Other Study ID Numbers: B.10.1.TKH.4.34.H.GP.0.01/172

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All Excel documents will be available (Patient initials and medical record numbers shaded XX). Demographics, BMI, malignancy risk factors, Bethesda and TI-RADS scores and final histopathology reports
• IPD Sharing Time Frame: June 01, 2020
• IPD Sharing Access Criteria: Contact for all available forms by email Open to all centers (especially for Black Sea and Estern European centers, but not limited to)
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Study Data/Documents

1. Principal investigator data

Drug and device information, study documents

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