DNA Methylation Testing for Thyroid Nodules

Overseen by John H. Yim

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: City of Hope Medical Center

Disqualifiers: Children

No Placebo Group

Trial Summary

What is the purpose of this trial?

This clinical trial evaluates deoxyribonucleic acid (DNA) methylation signatures in diagnosing and managing thyroid nodules. The purpose of this research is to develop a new test for thyroid cancer. This test will use needle biopsies (small collections of tissue with a needle) from the thyroid to determine whether the participant has a malignant (cancer) or benign (not showing cancer) thyroid tumor. The information learned from this trial may help develop a more accurate test so that patients do not have unnecessary surgeries for nodules that are thought to be suspicious but are actually benign.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment DNA Methylation Testing for Thyroid Nodules?

Research shows that combining DNA methylation markers with BRAF(V600E) mutation testing can improve the accuracy of diagnosing thyroid cancer from fine needle aspiration biopsy (FNAB) samples, helping to distinguish between cancerous and non-cancerous thyroid nodules. ^{1 2 3 4 5}

Is DNA methylation testing for thyroid nodules safe?

Fine-needle aspiration biopsy (FNAB), which is part of the DNA methylation testing process for thyroid nodules, is considered safe and reliable. It is a minimally invasive procedure used to assess thyroid nodules for cancer risk. ^{1 3 6 7 8}

How does DNA Methylation Testing for Thyroid Nodules differ from other treatments?

DNA Methylation Testing for Thyroid Nodules is unique because it uses molecular markers to analyze DNA changes, helping to distinguish between cancerous and non-cancerous thyroid nodules. This approach can improve diagnostic accuracy and potentially reduce unnecessary surgeries compared to traditional methods like cytology, which often have indeterminate results. ^{1 4 8 9 10}

Research Team

John H. Yim

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with thyroid nodules who are undergoing needle biopsies. Participants must be able to give informed consent and have the capacity to make decisions about their healthcare. Children are excluded because the biology of their thyroid nodules differs from that of adults.

Inclusion Criteria

I am over 18 years old.

My gender, race, or ethnicity does not limit my participation.

I am mentally capable and scheduled for a thyroid biopsy.

Exclusion Criteria

I am an adult.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic

Participants undergo needle biopsy for collection of tissue samples, which are analyzed using DDMS-2

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after diagnostic procedures

Up to 5 years

Treatment Details

Interventions

• Diagnostic Procedure (Diagnostic Test)
• Needle Biopsy (Procedure)

Trial Overview The study is testing a new diagnostic method using DNA methylation signatures from needle biopsy samples to distinguish between malignant (cancerous) and benign (non-cancerous) thyroid tumors, aiming to reduce unnecessary surgeries.

Participant Groups

Group I: Diagnostic (needle biopsy, DDMS-2) Experimental Treatment 3 Interventions

Patients undergo needle biopsy for collection of tissue samples. Tissue samples are analyzed using DDMS-2. Patients' medical records are also reviewed.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

The study analyzed fine needle aspiration biopsies (FNABs) from 117 patients and found that combining BRAF(V600E) mutation detection with DNA methylation markers significantly improved the diagnostic accuracy for papillary thyroid cancer (PTC).

BRAF(V600E) mutations were present in 71.4% of FNABs from patients with PTC, and specific methylation patterns of genes like DAPK1 and RASSF1A further distinguished malignant from benign nodules, enhancing the sensitivity and specificity of the diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies. Zhang, B., Liu, S., Zhang, Z., et al.[2021]

In a study of 66 patients with solitary thyroid nodules diagnosed as follicular neoplasms, intraoperative frozen-section analysis did not significantly improve the diagnosis of malignancy compared to existing clinical and cytological data.

Out of 64 deferred cases, only 15 were found to be malignant upon final pathology, indicating that routine frozen-section analysis may not be beneficial for distinguishing between benign and malignant follicular lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frozen section in a cytological diagnosis of thyroid follicular neoplasm. Alonso, N., Lucas, A., Salinas, I., et al.[2004]

In a study of 505 patients undergoing fine needle aspiration biopsy (FNAB) for thyroid nodules, the specimen adequacy ratio was found to be 85.3%, with larger nodules yielding more diagnostic samples (6.00 mL vs. 3.05 mL for non-diagnostic samples).

Predominantly solid nodules had better specimen adequacy (87.8%) compared to predominantly cystic nodules (75.3%), and cystic nodules took longer for definitive cytological diagnosis (376 seconds vs. 294 seconds for solid nodules), suggesting that repeated sampling may be necessary for cystic nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time? Cengic, I., Tureli, D., Ozden, F., et al.[2015]

About 15-30% of thyroid nodules are classified as indeterminate after fine-needle aspiration biopsy (FNAB), and understanding their molecular causes can help reduce unnecessary surgeries.

Current molecular tests, including mutation detection and gene expression analysis, show promise in improving the diagnosis of thyroid cancer in indeterminate cases, but more validation and local data are needed before they can be routinely used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can current molecular tests help in the diagnosis of indeterminate thyroid nodule FNAB? Ferraz, C.[2023]

Fine needle biopsy (FNB) is the safest and most effective method for evaluating thyroid nodules, with specific sampling techniques recommended to minimize false negatives, such as taking at least 6 aspirates and ensuring adequate benign cell clusters.

FNB results can be reliable enough to guide surgical decisions, and patients with benign diagnoses should be monitored, with re-biopsy recommended for nodules that do not shrink after one year of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fine needle biopsy diagnosis of thyroid nodules. Perspective. Hamburger, JI.[2016]

In a study of 474 patients with thyroid nodules ≥4 cm that had benign fine-needle aspiration biopsies, 5.3% were found to be malignant upon surgery, highlighting the potential for false negatives in FNAB results.

Younger patients (under 55 years old) had a significantly higher risk of malignancy (7.7%) compared to older patients (2.0%), indicating that age is an important factor in assessing the risk of malignancy in large thyroid nodules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule? Sutton, W., Canner, JK., Rooper, LM., et al.[2022]

Sequential fine-needle aspiration biopsy (FNAB) significantly improves the accuracy, sensitivity, and specificity of diagnosing thyroid nodules, with accuracy increasing by 22.6% and sensitivity by 13.8% compared to single FNABs.

While sequential FNABs are more costly (70% higher per patient), they reduce false positive/negative results by 14.2% and eliminate nondiagnostic results, potentially leading to lower overall healthcare costs by improving treatment selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease. Furlan, JC., Bedard, YC., Rosen, IB.[2018]

A new diagnostic tool using DNA methylation biomarkers can effectively differentiate between benign and malignant thyroid lesions, achieving up to 94.3% sensitivity and 82.4% specificity in identifying thyroid cancers.

This tool shows promise in preoperative screening, potentially reducing unnecessary surgeries for patients with thyroid nodules, especially in cases with indeterminate cytology, where it demonstrated 100% sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions. Barros-Filho, MC., Dos Reis, MB., Beltrami, CM., et al.[2020]

Molecular testing has become a crucial part of managing thyroid nodules, especially for those with indeterminate biopsy results, as it helps clarify the risk of malignancy and guides treatment decisions.

Advancements in understanding the genetic landscape of thyroid cancers, particularly papillary thyroid carcinoma, have improved the accuracy of molecular tests, allowing for more personalized and effective management strategies for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Molecular Diagnostics in Thyroid Pathology: A Review. Alzumaili, B., Sadow, PM.[2023]

A new molecular diagnostic test for thyroid cancer, based on DNA methylation analysis of 109 thyroid tissues, shows significant differences between benign nodules, adjacent tissues, and cancerous tissues, leading to improved diagnostic accuracy.

In a validation cohort of 65 thyroid nodules, the test demonstrated exceptional performance with 100% sensitivity and 97% specificity, indicating it can accurately identify cancerous nodules while minimizing unnecessary surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics. Yim, JH., Choi, AH., Li, AX., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Analysis of BRAF(V600E) mutation and DNA methylation improves the diagnostics of thyroid fine needle aspiration biopsies. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Frozen section in a cytological diagnosis of thyroid follicular neoplasm. [2004]

3. England pubmed.ncbi.nlm.nih.gov

Thyroid fine needle aspiration biopsy: do nodule volume and cystic degeneration ratio affect specimen adequacy and cytological diagnosis time? [2015]

4. Brazil pubmed.ncbi.nlm.nih.gov

Can current molecular tests help in the diagnosis of indeterminate thyroid nodule FNAB? [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Fine needle biopsy diagnosis of thyroid nodules. Perspective. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule? [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

DNA Methylation-Based Method to Differentiate Malignant from Benign Thyroid Lesions. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Update on Molecular Diagnostics in Thyroid Pathology: A Review. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics. [2020]