Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Multitarget Tyrosine Kinase Inhibitors
  Patients with or without actionable genomic alterations may receive a multikinase inhibitor (e.g., lenvatinib or anlotinib) as neoadjuvant therapy.
• Препарат 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.
• Препарат RET Inhibitor
  Patients with RET fusion may receive a selective RET inhibitor (e.g., selpercatinib).
• Препарат PD(L)-1 inhibitor
  In selected cases, combination regimens incorporating immunotherapy may be considered.
• Процедура 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.
• Процедура Surgery
  Patients considered resectable after neoadjuvant therapy will undergo definitive surgery, as determined by consensus of the multidisciplinary team (MDT).
• Процедура Surgery
  Patients deemed resectable at baseline will undergo immediate surgery based on MDT consensus and informed patient preference.

Первичные конечные точки

• Radiographic Response [Срок оценки: From baseline to preoperative imaging assessment after neoadjuvant therapy.]
• Pathologic Response [Срок оценки: At the time of surgery, based on postoperative pathological evaluation.]
• Progression-Free Survival (PFS) [Срок оценки: From the date of surgery until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.]

Вторичные конечные точки (6)

• Biochemical Response [Срок оценки: From 4 weeks to 12 months after surgery.]
• R0/1 Resection Rate [Срок оценки: At the time of surgery.]
• Change in Surgical Complexity and Morbidity Score [Срок оценки: From baseline to preoperative imaging assessment after neoadjuvant therapy.]
• Surgery Related Adverse Events [Срок оценки: During surgery or within 30 days after surgery.]
• Incidence of Grade ≥ 3 Neoadjuvant Treatment-Related Advert Events [Срок оценки: From baseline to 30 days after the last dose of neoadjuvant therapy.]
• Overall Survival (OS) [Срок оценки: From the date of surgery to death from any cause, assessed up to 24 months.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Китай · 1 центр

• Fujian Medical University Union Hospital — Фучжоу

Идентификаторы

NCT: NCT07419932 · FMUUH-LACTCS002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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