Clinical Value of Patient‐Derived Tumor Organoids in Guiding Precision Chemotherapy for Locally Advanced Thyroid Cancer: A Single‐Center, Single‐Arm, Phase 2 Trial

ABSTRACT While thyroid cancer generally carries a favorable prognosis, the 5‐year survival rate for advanced cases, particularly poorly differentiated and anaplastic subtypes, remains below 20%. The latest guidelines recommend conservative use of chemotherapy in thyroid cancer, primarily due to the absence of reliable efficacy prediction systems. Tumor‐derived organoid‐based strategies represent a powerful tool for assessing individual‐level drug sensitivity and identifying novel treatment regimens. This prospective single‐arm cohort study enrolled 25 patients. Thyroid tumor tissue was procured via ultrasound‐guided core needle biopsy, and organoids were established using a modified Matrigel‐air‐liquid interface culture method. Drug sensitivity testing encompassed clinically relevant chemotherapeutic agents, utilizing IC50 values as the primary parameter for formulating individualized regimens. Eventually, the objective response rate (ORR) of 15 patients who received the recommended regimens reached 53.3%, among which the ORR of patients with anaplastic thyroid carcinoma (ATC) was as high as 87.5%. The tumor diameters of the patients were significantly reduced, with a median reduction of 40.32% (IQR: 7.89%–65.22%), and 80% of the patients had a progression‐free survival (PFS) exceeding 6 months. This preliminary study confirmed the feasibility of extracting and culturing tumor organoids from patients' tumor lesions, which can serve as an effective tool for chemotherapy drug screening, highlighting the potential of precision medicine in individualized chemotherapy for locally advanced thyroid carcinoma (LATC).