Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer (NeoLATC)

February 12, 2026 updated by: wenxin zhao, Fujian Medical University

Biochemical, Radiological and Pathological Responses to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer: A Multicenter Study

This multicenter observational study aims to evaluate the safety and efficacy of neoadjuvant therapy in patients with locally advanced thyroid cancer, focusing on imaging, biochemical, and pathological responses, as well as short-term surgical outcomes and long-term prognosis.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Locally advanced thyroid cancer (LATC) is characterized by tumors that extensively invade critical adjacent structures, leading to a poor prognosis and significantly contributing to thyroid cancer-related mortality. In recent years, neoadjuvant therapy has been increasingly applied to LATC, resulting in tumor downstaging and improved resectability in some patients. However, challenges remain in optimizing radical treatment strategies and improving long-term outcomes for LATC patients.

This study aims to systematically analyze the clinical data of LATC patients who underwent neoadjuvant treatment followed by radical thyroidectomy, with a focus on the following objectives: (1) to summarize the imaging, biochemical, and pathological responses to neoadjuvant therapy and investigate associated recurrence risk stratification; (2) to evaluate the short-term efficacy of surgical outcomes (e.g., R0/R1 resection rates, perioperative complications) and long-term prognosis (e.g., survival outcomes), with comparisons to a control cohort of patients undergoing upfront surgery.

Furthermore, the investigators will examine changes in the profiles and functions of immune cells within tumors, lymph nodes, and peripheral blood after the interventions, and assess their correlation with neoadjuvant response and prognosis. Additionally, based on multi-omics features, including pathological histology, ultrasonomics, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics, the study aims to identify potential biological markers for tumor resistance mechanisms and explore biomarkers that could inform clinical decision-making.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China, 350001
        • Recruiting
        • Fujian Medical University Union Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients diagnosed with LATC may be managed with either neoadjuvant therapy followed by surgery or upfront surgery, depending on resectability and multidisciplinary team assessment.

Description

Inclusion Criteria:

  • Age ≥ 14 years at enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Histologically or cytologically confirmed thyroid carcinoma, including differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC).
  • LATC defined as clinical stage T4N0-1 at baseline, as confirmed by a multidisciplinary thyroid oncology board.
  • For patients with distant metastasis, the potential benefit from surgical intervention must be documented by the treating team.
  • Presence of at least one measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Normal function of major organs.
  • Written informed consent obtained.

Exclusion Criteria:

  • Patients who refuse tumor tissue biopsy or surgery.
  • Prior thyroid or major neck surgery.
  • History of other treatments for cancer, including surgery, chemotherapy, radiotherapy, or molecular targeted therapy, that may affect the current treatment plan.
  • Concurrent active malignancies.
  • Uncontrolled systemic diseases, including diabetes, hypertension, etc.
  • Pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Neoadjuvant Treatment Group
Participants will undergo neoadjuvant treatment with multikinase inhibitors (mTKIs), specific receptor inhibitors (including RET inhibitors or BRAF ± MEK inhibitors), or combination regimens containing a PD-1 inhibitor. All regimens will be administered for at least two cycles prior to surgery.
Drug: Multitarget Tyrosine Kinase Inhibitors
Patients with or without actionable genomic alterations may receive a multikinase inhibitor (e.g., lenvatinib or anlotinib) as neoadjuvant therapy.
Other Names:
  • Lenvatinib
  • Anlotinib
Drug: BRAF inhibitor dabrafenib and MEK inhibitor trametinib
Patients with BRAF V600E mutation may receive combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib.
Other Names:
  • Trametinib
  • Dabrafenib
Drug: RET Inhibitor
Patients with RET fusion may receive a selective RET inhibitor (e.g., selpercatinib).
Other Names:
  • Selpercatinib
  • Pralsetinib
Drug: PD(L)-1 inhibitor
In selected cases, combination regimens incorporating immunotherapy may be considered.
Other Names:
  • Pembrolizumab
  • Nivolumab
Procedure: Biopsy
While fine-needle aspiration (FNA) is the standard initial diagnostic modality for thyroid nodules, core needle biopsy (CNB) is performed to obtain tissue cores for histological subtyping and molecular profiling in locally advanced cases.
Other Names:
  • Core Needle Biopsy
  • Fine-needle Aspiration
Procedure: Surgery
Patients considered resectable after neoadjuvant therapy will undergo definitive surgery, as determined by consensus of the multidisciplinary team (MDT).
Procedure: Surgery
Patients deemed resectable at baseline will undergo immediate surgery based on MDT consensus and informed patient preference.
Upfront Surgery Group
The participants in this group will undergo radical surgery directly after the diagnosis of LATC, based on MDT consensus and patient's preference.
Procedure: Biopsy
While fine-needle aspiration (FNA) is the standard initial diagnostic modality for thyroid nodules, core needle biopsy (CNB) is performed to obtain tissue cores for histological subtyping and molecular profiling in locally advanced cases.
Other Names:
  • Core Needle Biopsy
  • Fine-needle Aspiration
Procedure: Surgery
Patients considered resectable after neoadjuvant therapy will undergo definitive surgery, as determined by consensus of the multidisciplinary team (MDT).
Procedure: Surgery
Patients deemed resectable at baseline will undergo immediate surgery based on MDT consensus and informed patient preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic Response
Time Frame: From baseline to preoperative imaging assessment after neoadjuvant therapy.
Radiographic response of tumors and lymph nodes to neoadjuvant treatment will be assessed using contrast-enhanced computed tomography (CT) and defined by RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions. Partial response (PR) is defined as ≥30% decrease in the sum of the longest diameter of target lesion; progressive disease (PD) as ≥20% increase in the sum of the longest diameter of target lesions. Stable disease (SD) is defined as <20% increase and <30% decrease in the sum of the longest diameter of target lesions. The objective response rate (ORR) will be calculated as the proportion of patients achieving CR or PR.
From baseline to preoperative imaging assessment after neoadjuvant therapy.
Pathologic Response
Time Frame: At the time of surgery, based on postoperative pathological evaluation.
Pathologic response in resected tumors and lymph nodes will be assessed on hematoxylin and eosin (H&E)-stained slides of the entire tumor bed and all sampled lymph nodes. All slides will be digitally scanned and independently reviewed by two pathologists. Pathological complete response (pCR) is defined as the absence of viable tumor cells in all examined slides. For this study, pathological partial response (pPR) is defined as <50% viable residual tumor, and pathological non-response (pNR) as ≥50% viable residual tumor in the resected specimen.
At the time of surgery, based on postoperative pathological evaluation.
Progression-Free Survival (PFS)
Time Frame: From the date of surgery until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Time from surgery to the earliest date of disease progression or all-cause death.
From the date of surgery until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical Response
Time Frame: From 4 weeks to 12 months after surgery.

Serum thyroglobulin (Tg) levels in patients with DTC and serum calcitonin and carcinoembryonic antigen (CEA) levels in patients with MTC will be measured after definitive surgery. Levels will be:

  1. compared across subgroups defined by radiographic response (per RECIST v1.1) and pathologic response (e.g., pCR, pPR, pNR) within the neoadjuvant therapy cohort; and
  2. compared between the neoadjuvant therapy plus surgery group and the upfront surgery group at matched postoperative timepoints.
From 4 weeks to 12 months after surgery.
R0/1 Resection Rate
Time Frame: At the time of surgery.
Percentage of resected participants with no residual tumor (R0) or microscopic residual tumor (R1) on final pathology.
At the time of surgery.
Change in Surgical Complexity and Morbidity Score
Time Frame: From baseline to preoperative imaging assessment after neoadjuvant therapy.
The MGH/MEE-MSK-MD Anderson Surgical Morbidity Complexity Score (SMCS) will be used to assess surgical complexity. The SCMS is a validated 5-level scale [mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)] that quantifies surgical complexity based on preoperative radiographic assessment of tumor involvement with critical neck structures.、 The SMCS will be collected at enrollment (baseline imaging) and prior to surgery using restaging imaging. The change in SCMS will be reported as the median SCMS value.
From baseline to preoperative imaging assessment after neoadjuvant therapy.
Surgery Related Adverse Events
Time Frame: During surgery or within 30 days after surgery.
Surgery related adverse events (SRAEs) are defined as complications occurring during surgery or within 30 days postoperatively. Postoperative complications will be documented and classified according to the Clavien-Dindo grading system, including but not limited to hemorrhage, hypoparathyroidism, vocal cord palsy, chyle leakage, and wound infection.
During surgery or within 30 days after surgery.
Incidence of Grade ≥ 3 Neoadjuvant Treatment-Related Advert Events
Time Frame: From baseline to 30 days after the last dose of neoadjuvant therapy.
Number and percentage of participants experiencing Grade 3 or higher adverse events, assessed according to CTCAE v5.0.
From baseline to 30 days after the last dose of neoadjuvant therapy.
Overall Survival (OS)
Time Frame: From the date of surgery to death from any cause, assessed up to 24 months.
Time from surgery to all-cause death, with survivors censored at the date of last follow-up.
From the date of surgery to death from any cause, assessed up to 24 months.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Microenvironment and Immune Profiling
Time Frame: From baseline (pre-neoadjuvant therapy biopsy) to surgery.
Changes in tumor immune cell composition following neoadjuvant therapy, assessed by single-cell RNA sequencing of tumor tissue obtained at baseline (pre-neoadjuvant biopsy) and at surgery. The outcome measure will be the change in the proportion of major immune cell subsets within the tumor microenvironment.
From baseline (pre-neoadjuvant therapy biopsy) to surgery.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fujian Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 23, 2025

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

February 6, 2026

First Submitted That Met QC Criteria

February 12, 2026

First Posted (Actual)

February 19, 2026

Study Record Updates

Last Update Posted (Actual)

February 19, 2026

Last Update Submitted That Met QC Criteria

February 12, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMUUH-LACTCS002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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