Immediate biopsy versus active ultrasound monitoring for suspicious thyroid nodules

ThyRoid Active Monitoring and Intervention Longitudinal (TRAIL) Study: Feasibility and Pilot

This will try immediate biopsy versus careful ultrasound monitoring to see which causes less anxiety and better thyroid-related quality of life for adults with newly found suspicious thyroid nodules (TI‑RADS 4–5) that are 2 cm or smaller.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dartmouth-Hitchcock Medical Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Lebanon, New Hampshire)
• Trial ID: NCT06220656 on ClinicalTrials.gov

What this trial studies

This is a randomized pilot comparing two management strategies for newly identified thyroid nodules judged likely to be cancerous by ultrasound. Adults with TI‑RADS 4 or 5 nodules ≤2 cm who would ordinarily be offered biopsy are randomized to immediate biopsy (usual care) or active monitoring with serial ultrasound and close clinical follow-up. The co-primary outcomes include anxiety at 6 months measured by Anxiety-CA and thyroid-specific quality of life measures, with feasibility endpoints for a larger trial. The study is conducted at Dartmouth‑Hitchcock Medical Center and is intended to inform whether surveillance can be a safe, lower-anxiety option for selected patients.

Who should consider this trial

Good fit: Adults aged 18 or older with a newly found TI‑RADS 4 or 5 thyroid nodule ≤2 cm who are being considered for biopsy and do not have symptoms like visible or bothersome nodules or difficulty swallowing.

Not a fit: Patients with symptomatic or clearly bothersome nodules, nodules larger than 2 cm, prior non‑papillary thyroid cancer, prior neck radiation, removed thyroid gland, or those who need or prefer immediate tissue diagnosis are unlikely to benefit from monitoring here.

Why it matters

Potential benefit: If successful, this approach could reduce unnecessary biopsies and related harms while lowering patient anxiety and preserving quality of life.

How similar studies have performed: Active surveillance has shown success for small papillary thyroid cancers in multiple cohorts, but using surveillance instead of immediate biopsy for TI‑RADS 4–5 nodules is less well studied and remains investigational.

Eligibility criteria

Inclusion Criteria:

* Participants must be ≥18 years of age.
* Participants must be able and willing to provide informed consent or have a surrogate capable of providing same.
* Participants must be absent of symptoms referable to the nodule: dysphagia or nodule physically visible and/or bothersome to patient.
* Participants' thyroid nodule must have a TI-RADS rating of 4 or 5.
* Participants thyroid nodule must be ≤2 cm in largest diameter.
* Participants must be being considered for biopsy.
* Participants with a prior history of papillary thyroid cancer are eligible.

Exclusion Criteria:

Patients who fall into one of the following categories will NOT be eligible for this study:

* Adults who are unable to provide informed consent.
* Patients for whom biopsy is not a consideration.
* Patients with a prior history of thyroid cancer other than papillary thyroid cancer.
* Patients with a history of radiation to the neck.
* Patients who are athyroidal (thyroid gland has been removed or patient has only lingual thyroid tissue).
* Patients who have ultrasound evidence of one or more of the following:
* Airway invasion of the nodule.
* Nodule adjacency to/invading the recurrent nerve.
* Extra-thyroidal invasion by the nodule.
* Patients who have metastasis to cervical lymph nodes (confirmed by needle biopsy if ultrasound suspicious), distant metastases, if identified) testing not required, not usual care)
* Patients who have already had a biopsy of the nodule being considered for inclusion in the study.

TRAIL Pilot Integrated QRI: Inclusion/Exclusion Criteria

Inclusion Criteria for Study Patient Participants:

* Participants must meet the eligibility requirements above and will be or have been approached about enrolling in the pilot study.
* Participants must be willing to allow audio recorder presence and / or willing to be interviewed by the QRI team.

Exclusion Criteria for Study Patient Participants:

-Patients who are not willing to allow audio recorder presence and/or not willing to be interviewed by QRI team will be excluded from this study.

Inclusion Criteria for Study Staff Participants:

* Staff must be willing to audio record their communications with patients about enrolling in the study.
* Staff must be willing to participate in interviews with QRI team about their views of the study.

Exclusion Criteria for Study Staff Participants:

-Staff members who are not willing to participate in audio taping of recruitment discussions and/or interviews with QRI team about their views of the study will be excluded.

Where this trial is running

Lebanon, New Hampshire

• Dartmouth Hitchcock Medical Center — Lebanon, New Hampshire, United States (Recruiting)

Study contacts

• Principal investigator: Louise Davies, MD, MS — Dartmouth-Hitchcock Medical Center
• Study coordinator: Michaela M Geffert, BS

Conditions Thyroid Nodule; Thyroid Neoplasms; Thyroid Cancer