Molecular Analysis for Thyroid Cancer

(MAPS Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, Los Angeles

Disqualifiers: Prior thyroid operation, Metastatic disease, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Ideal surgical extent for differentiated thyroid cancer remains unclear. Routine use of molecular analysis in biopsy-proven thyroid cancer could provide important prognostic information to help guide extent of surgery - thyroid lobectomy versus total thyroidectomy. This is a pilot feasibility study for the use of routine molecular analysis in Bethesda V and VI thyroid cancers, with randomization of the intermediate-molecular risk subgroup to thyroid lobectomy and total thyroidectomy. The investigators hypothesize that patients will 1) agree to preoperative molecular analysis, and 2) 50% of intermediate-risk patients will agree to and follow through with randomization. This will be a pilot study for a future randomized controlled trial (RTC) to compare between the two surgical approaches in intermediate-molecular risk thyroid cancer.

Do I need to stop my current medications for the trial?

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

What data supports the effectiveness of the treatment Molecular Analysis for Thyroid Cancer?

Research shows that molecular testing can help identify specific markers in thyroid cancer, which can improve decision-making and potentially spare patients from unnecessary surgeries. It can also help determine the best surgical approach, making treatment more personalized and effective. ^{1 2 3 4 5}

Is molecular analysis for thyroid cancer safe for humans?

The research does not specifically address the safety of molecular analysis for thyroid cancer, but it is widely used in clinical settings to help make decisions about surgery and treatment, suggesting it is generally considered safe. ^{1 2 5 6 7}

How is the Molecular Analysis for Thyroid Resection treatment different from other thyroid cancer treatments?

Molecular Analysis for Thyroid Resection is unique because it uses molecular testing to identify specific genetic markers in thyroid nodules, which helps doctors decide if surgery is necessary and what type of surgery to perform. This approach can prevent unnecessary surgeries and tailor treatment plans based on the tumor's genetic profile, unlike traditional methods that rely solely on imaging and biopsy results. ^{1 2 4 8 9}

Research Team

Eligibility Criteria

This trial is for individuals with a confirmed diagnosis of papillary thyroid cancer or other thyroid diseases, specifically those classified as Bethesda V and VI. Participants must be willing to undergo preoperative molecular analysis to guide the surgical approach: partial or complete removal of the thyroid.

Inclusion Criteria

I am 18 years old or older.

English-speaking

My thyroid nodule is classified as high risk and is between 1-4cm.

Exclusion Criteria

My thyroid cancer has spread beyond the thyroid or to lymph nodes.

I have had surgery on my thyroid.

My cancer has spread to distant parts of my body.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Molecular Testing

Participants undergo Thyroseq molecular testing to stratify thyroid cancer risk

4 weeks

1 visit (in-person)

Randomization and Treatment

Intermediate-risk patients are randomized to thyroid lobectomy or total thyroidectomy

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Routine follow-up visits

Treatment Details

Interventions

• Molecular Analysis for Thyroid Resection (Procedure)

Trial Overview The study is testing whether routine molecular analysis before surgery can help decide if patients should have part (thyroid lobectomy) or all (total thyroidectomy) of their thyroid removed. It's a pilot study that randomly assigns some patients to either surgery based on their molecular risk level.

Participant Groups

Group I: Thyroid Lobectomy Active Control 1 Intervention

Randomization Protocol Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further. Peri-operative Protocol Thyroid Lobectomy Patients undergoing thyroid lobectomy will have the thyroid lobe containing the cancer removed in the standard surgical technique. These operations will be performed at either the UCLA Health Westwood Ambulatory Surgery Center, UCLA Ronald Reagan Medical Center, or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

Group II: Total Thyroidectomy Active Control 1 Intervention

Randomization Protocol Patients with intermediate molecular-risk thyroid nodules will be randomized to thyroid lobectomy or total thyroidectomy. We will perform a 1:1 randomization in a consecutive manner. Patients will be informed of what operation they will receive and providers will also be aware what operation was performed as it dictates care moving forward. Details of operative management will be discussed further. Total Thyroidectomy and Completion Thyroidectomy Patients undergoing total thyroidectomy will have their whole thyroid gland removed in the standard surgical technique. Patients undergoing a completion thyroidectomy will have their remaining thyroid lobe removed. These operations will be performed at UCLA Ronald Reagan Medical Center or UCLA Santa Monica Medical Center. Patients will undergo our usual postoperative care.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Dr. Thomas Rando

University of California, Los Angeles

Chief Medical Officer since 2023

MD from UCLA

Amir Naiberg

University of California, Los Angeles

Chief Executive Officer since 2024

JD from UCLA

Findings from Research

Molecular testing for thyroid cancer can effectively reclassify over 50% of patients with indeterminate thyroid nodules, helping to identify benign cases and potentially avoiding unnecessary surgeries.

Understanding the molecular risk profile of thyroid nodules, along with clinical and radiologic features, can guide better surgical decisions for patients with suspicious or positive malignancy results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada. Rajab, M., Payne, RJ., Forest, VI., et al.[2022]

Molecular profiling tests for thyroid nodules are becoming essential tools for surgeons, particularly in making decisions about surgery and the extent of resection, especially for cases with indeterminate fine-needle aspiration cytology.

The effectiveness of these diagnostic tests is highly dependent on the prevalence of cancer in specific cytologic categories at individual medical centers, highlighting the importance of understanding local cancer rates to accurately interpret test results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making. Ferris, RL., Baloch, Z., Bernet, V., et al.[2023]

In a study of 578 thyroid cancer patients, molecular testing categorized tumors into three risk groups, revealing that higher risk groups were associated with more aggressive tumor characteristics and a higher likelihood of recurrence.

Patients with molecular risk group-high cancers had a significantly increased risk of recurrence compared to those in the intermediate and low groups, with hazard ratios indicating a fourfold and fivefold increase in recurrence risk, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes. Liu, JB., Ramonell, KM., Carty, SE., et al.[2022]

Molecular testing can enhance the assessment of malignancy risk in indeterminate thyroid nodules, potentially guiding better surgical decisions, although its impact on modifying surgery extent remains uncertain.

Integrating molecular characterization into clinical management for advanced thyroid cancers can help identify actionable mutations and improve treatment outcomes while minimizing toxicity, especially with the availability of selective kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer. Valderrabano, P., Eszlinger, M., Stewardson, P., et al.[2023]

Molecular genetic analysis of thyroid nodules, particularly through fine-needle aspiration biopsy (FNAB), is becoming an important tool in diagnosing thyroid cancer and determining which patients may need surgery versus those who can be monitored safely.

Understanding the genetics of thyroid cancer can help in personalizing treatment plans and improving management strategies for patients, as it provides insights into prognosis and the likelihood of recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science. Richmond, BK., Gallimore, J.[2023]

Molecular testing for thyroid nodules with malignant cytology (Bethesda VI) shows a high BRAF mutation detection rate of 70%, indicating its potential value in risk assessment for elective surgeries during a pandemic.

Incorporating additional gene alterations and classifiers can significantly enhance diagnostic accuracy, raising the detection rate of actionable mutations to as high as 95%, which supports better surgical and therapeutic decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative molecular testing in thyroid nodules with Bethesda VI cytology: Clinical experience and review of the literature. Labourier, E., Fahey, TJ.[2021]

A new molecular test analyzing the expression of 19 genes has been developed to help distinguish between malignant and benign thyroid tumors, validated in a study of 730 patients with thyroid nodules.

In a separate analysis of 200 papillary thyroid carcinomas, significant genetic differences were found, with over 75% of invasive tumors showing specific mutations, which could aid in identifying tumors with a higher risk of metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analyses of thyroid tumors for diagnosis of malignancy on fine-needle aspiration biopsies and for prognosis of invasiveness on surgical specimens. Rousset, B., Ziercher, L., Borson-Chazot, F.[2019]

In a study of 103 patients with malignant thyroid tumors, specific mutations like BRAF V600E, RET/PTC1 rearrangement, and TERT promoter mutations were linked to more aggressive tumor behavior, including extra-thyroidal extension and lymph node metastasis.

Molecular testing for these mutations can help predict the aggressiveness of thyroid cancers, which may guide surgical decisions and treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mutations as a possible factor for determining extent of thyroid surgery. Krasner, JR., Alyouha, N., Pusztaszeri, M., et al.[2020]

Molecular testing for mutations like BRAF, RAS, and RET/PTC in thyroid cancer can help accurately diagnose and manage differentiated thyroid cancer, potentially reducing unnecessary surgeries by identifying benign cases.

About 20% to 30% of certain thyroid lesions are malignant, while 70% to 80% of diagnostic thyroid surgeries reveal benign conditions, highlighting the importance of molecular testing to improve patient outcomes and tailor treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and management of differentiated thyroid cancer using molecular biology. Witt, RL., Ferris, RL., Pribitkin, EA., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Testing for Thyroid Nodules: The Experience at McGill University Teaching Hospitals in Canada. [2022]

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

American Thyroid Association Statement on Surgical Application of Molecular Profiling for Thyroid Nodules: Current Impact on Perioperative Decision Making. [2023]

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

Association of comprehensive thyroid cancer molecular profiling with tumor phenotype and cancer-specific outcomes. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Clinical value of molecular markers as diagnostic and prognostic tools to guide treatment of thyroid cancer. [2023]

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

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science. [2023]

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

Preoperative molecular testing in thyroid nodules with Bethesda VI cytology: Clinical experience and review of the literature. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Molecular analyses of thyroid tumors for diagnosis of malignancy on fine-needle aspiration biopsies and for prognosis of invasiveness on surgical specimens. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Molecular mutations as a possible factor for determining extent of thyroid surgery. [2020]

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

Diagnosis and management of differentiated thyroid cancer using molecular biology. [2022]