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Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer

ConditionsThyroid CancerThyroid Neoplasms
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age14-80
SponsorFujian Medical University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial 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.

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

  • Multitarget Tyrosine Kinase Inhibitors

    Drug

    Patients with or without actionable genomic alterations may receive a multikinase inhibitor (e.g., lenvatinib or anlotinib) as neoadjuvant therapy.

  • BRAF inhibitor dabrafenib and MEK inhibitor trametinib

    Drug

    Patients with BRAF V600E mutation may receive combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib.

  • RET Inhibitor

    Drug

    Patients with RET fusion may receive a selective RET inhibitor (e.g., selpercatinib).

  • PD(L)-1 inhibitor

    Drug

    In selected cases, combination regimens incorporating immunotherapy may be considered.

  • Biopsy

    Procedure/Surgery

    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.

  • Surgery

    Procedure/Surgery

    Patients considered resectable after neoadjuvant therapy will undergo definitive surgery, as determined by consensus of the multidisciplinary team (MDT).

  • Surgery

    Procedure/Surgery

    Patients deemed resectable at baseline will undergo immediate surgery based on MDT consensus and informed patient preference.

Treatment groups

120 Participants
are divided into 2 treatment groups
Group A: Neoadjuvant Treatment Group6 interventions
Group B: Upfront Surgery Group2 interventions

Trial outcomes

Primary outcomes

1

Radiographic Response

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.

Time frame
From baseline to preoperative imaging assessment after neoadjuvant therapy.
2

Pathologic Response

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.

Time frame
At the time of surgery, based on postoperative pathological evaluation.
3

Progression-Free Survival (PFS)

Time from surgery to the earliest date of disease progression or all-cause death.

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.

Secondary outcomes

1

Biochemical Response

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.

Time frame
From 4 weeks to 12 months after surgery.
2

R0/1 Resection Rate

Percentage of resected participants with no residual tumor (R0) or microscopic residual tumor (R1) on final pathology.

Time frame
At the time of surgery.
3

Change in Surgical Complexity and Morbidity Score

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.

Time frame
From baseline to preoperative imaging assessment after neoadjuvant therapy.
4

Surgery Related Adverse Events

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.

Time frame
During surgery or within 30 days after surgery.

Other outcomes

1

Tumor Microenvironment and Immune Profiling

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.

Time frame
From baseline (pre-neoadjuvant therapy biopsy) to surgery.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fujian Medical University

Lead sponsor

Fujian Medical University Union Hospital

Sponsor institution

Source ClinicalTrials.gov
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