Response to Neoadjuvant Treatment in Locally Advanced Thyroid Cancer

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.

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.

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.