Biochemical, Radiological and Pathological Responses to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer: A Multicenter Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Radiographic Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 14 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 14 years at enrollment.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •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.
- •Normal function of major organs.
- •Written informed consent obtained.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Multitarget Tyrosine Kinase Inhibitors (Drug)
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.
干预措施: BRAF inhibitor dabrafenib and MEK inhibitor trametinib (Drug)
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.
干预措施: RET Inhibitor (Drug)
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.
干预措施: PD(L)-1 inhibitor (Drug)
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.
干预措施: Biopsy (Procedure)
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.
干预措施: Surgery (Procedure)
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.
干预措施: Biopsy (Procedure)
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.
干预措施: Surgery (Procedure)
结局指标
主要结局
Radiographic Response
时间窗: 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.
Pathologic Response
时间窗: 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.
Progression-Free Survival (PFS)
时间窗: 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.
次要结局
- R0/1 Resection Rate(At the time of surgery.)
- Biochemical Response(From 4 weeks to 12 months after surgery.)
- Change in Surgical Complexity and Morbidity Score(From baseline to preoperative imaging assessment after neoadjuvant therapy.)
- Surgery Related Adverse Events(During surgery or within 30 days after surgery.)
- Incidence of Grade ≥ 3 Neoadjuvant Treatment-Related Advert Events(From baseline to 30 days after the last dose of neoadjuvant therapy.)
- Overall Survival (OS)(From the date of surgery to death from any cause, assessed up to 24 months.)
研究者
wenxin zhao
Professor and Chief Surgeon, Department of Thyroid Surgery
Fujian Medical University Union Hospital