Efficacy of Irreversible Electroporation Ablation for Postoperative Recurrent or Metastatic Cervical Lymph Node Disease in Thyroid Cancer: A Prospective, Multicenter, Single-Arm, Exploratory Clinical Trial
This is a single-arm, open-label, multicenter, exploratory clinical trial designed to systematically evaluate the efficacy, safety, and patient benefit of ultrasound-guided irreversible electroporation (IRE) ablation for recurrent or metastatic cervical lymph node disease in patients with thyroid cancer after prior curative thyroid surgery and neck dissection. A total of 85 participants will be enrolled. After providing written informed consent, participants will enter a screening period of up to 28 days. During screening, baseline imaging of target lymph nodes will be performed (contrast-enhanced ultrasound or computed tomography), and patient-reported and clinician-reported assessments will be completed, including quality of life, pain, neck appearance, and, when applicable, voice-related outcomes. Laboratory testing and immunology samples will also be collected. Eligible participants will undergo the first IRE ablation on Day 0 under ultrasound guidance. Acute pain will be assessed using the Numeric Rating Scale (NRS) at 0, 4, 8, 24, 48, and 72 hours after the procedure, and all adverse events and device deficiencies will be recorded. The first imaging re-assessment will be performed at Day 30 (±7 days). If residual enhancement suggests incomplete ablation, one salvage IRE ablation may be performed within 14 days. After confirmation of no need for salvage ablation or after completion of salvage ablation, participants will enter follow-up. Follow-up visits will occur every 3 months starting from Month 3 after the first (or salvage) ablation and will continue until 24 months or until imaging progression, withdrawal, death, or loss to follow-up, whichever occurs first. Imaging assessments will be performed at each follow-up visit. At 12 months, the volume reduction rate (VRR), complete disappearance rate, and recurrence rate of treated lymph nodes will be assessed. Patient-reported outcomes (ThyPRO-39, EQ-5D-5L, neck appearance satisfaction visual analog scale) and clinician-reported scar assessment (Vancouver Scar Scale) will be repeated at Months 1, 3, 6, and 12, with the Voice Handicap Index-10 collected as needed. Laboratory tests (blood count, biochemistry, electrolytes) and immunology samples will be collected every 3 months. The primary efficacy endpoint is the lymph node volume reduction rate at 12 months after a single IRE ablation. Secondary efficacy endpoints include 12-month lymph node volume reduction rate after single and/or salvage ablation, complete disappearance rate and recurrence rate at 12 months, volume reduction rate at 12 months for lesions located in high-risk anatomical areas, progression-free survival and overall survival, and improvements in quality of life and cosmetic outcomes. Safety endpoints include the incidence of adverse events and serious adverse events graded by NCI CTCAE v5.0, device-related serious adverse events, acute pain tolerability (NRS area under the curve and the proportion of participants with NRS ≥4 of sustained duration), laboratory abnormalities, and changes in voice-related outcomes. Exploratory endpoints include longitudinal changes in immune cell subsets, immune checkpoint and inhibitory molecule expression, and serum cytokine/chemokine profiles. Adverse events will be followed from the last IRE procedure (including salvage ablation) through 12 months.
• 2: Age ≥ 18 years at the time of enrollment, male or female.
• 3: ECOG performance status score of 0 or 1.
• 4: Expected survival time ≥ 12 months.
• 5: Cervical lymph node metastases confirmed by pathology (core needle biopsy, fine-needle aspiration biopsy, or thyroglobulin testing in fine-needle aspiration washout fluid), and all of the following: ① Thyroid cancer has recurred/metastasized after standard thyroid lobectomy plus lymph node dissection; ② The number of lymph nodes on one side of the neck is ≤ 5, and the maximum long-axis diameter is \< 3.0 cm.
• 6: Not suitable for repeat surgical resection or the patient refuses repeat surgery, or \^131I therapy is ineffective or the patient refuses \^131I therapy.
• 7: Adequate organ function as defined below: a) Hematologic (no transfusion of blood components or use of hematopoietic growth factors within 7 days prior to initiation of study treatment): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (1,500/mm³); ii. Platelet count (PLT) ≥ 100 × 10\^9/L (100,000/mm³); iii. Hemoglobin ≥ 90 g/L. b) Renal: i. Calculated creatinine clearance (CrCl)\* ≥ 50 mL/min. CrCl (mL/min) is calculated using the Cockcroft-Gault formula: CrCl (mL/min) = {(140 - age) × body weight (kg) × F} / \[SCr (mg/dL) × 72\] where F = 1 for males and F = 0.85 for females; SCr = serum creatinine. ii. Urine protein ≤ 2+ (dipstick) or 24-hour urine protein \< 1.0 g. c) Hepatic: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN (upper limit of normal); for subjects with liver metastases or confirmed/suspected Gilbert's syndrome, TBil ≤ 3 × ULN; ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for subjects with liver metastases, AST and ALT ≤ 5 × ULN. d) Coagulation: International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) ≤ 1.5 × ULN. e) Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%.
• 8: Women of childbearing potential must undergo a urine or serum pregnancy test within 3 days prior to the first dose of study treatment (if the urine pregnancy test result cannot be definitively interpreted as negative, a serum pregnancy test must be performed, and the serum result shall prevail), and the result must be negative. If a woman of childbearing potential has sexual intercourse with a male partner who has not been surgically sterilized, she must use an acceptable method of contraception starting from screening and agrees to continue contraception for 180 days after the last dose of the study drug.
• 9: Male subjects who have not been surgically sterilized and have female partners of childbearing potential must use effective contraception from screening until 180 days after the last dose of the study drug.
• 10: The subject is willing and able to comply with the visit schedule, treatment regimen, laboratory examinations, and other requirements of the study.
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