Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Randomized, Single-center Exploratory Clinical Study
This is a single-center, open-label, randomized, controlled, exploratory clinical trial designed to evaluate the efficacy and safety of de-escalated surgery compared with standard surgery in patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who achieved a partial response (PR) or complete response (CR) after neoadjuvant immunochemotherapy. Eligible patients will be randomly assigned in a 1:1 ratio to either the de-escalated surgery group (experimental) or the standard surgery group (control). The de-escalated surgery group will undergo limited tumor resection and selective neck dissection based on clinical and imaging response, while preserving important anatomical structures and functions when feasible. The control group will receive standard surgical treatment following NCCN guidelines. All patients will be evaluated using RECIST 1.1 criteria for radiological response and will undergo enhanced CT or MRI at baseline, before the second cycle of neoadjuvant therapy, within one week before surgery, 30 days after surgery, and every 3 months thereafter until 2 years post-surgery, disease recurrence, death, or study completion. The study aims to assess whether de-escalated surgery can achieve similar oncologic outcomes while improving postoperative function and quality of life. The primary endpoints are disease-free survival (DFS), health-related quality of life (HRQoL), and 3- and 5-year overall survival rates (OS rate). A total of 60 patients will be enrolled over a 3-year period, with 30 in each group.
• Patients diagnosed with stage III-IVa head and neck squamous cell carcinoma (HNSCC) according to the AJCC 8th edition TNM staging system, who have achieved a partial response (PR) or complete response (CR) after receiving neoadjuvant immunochemotherapy consisting of a PD-1 inhibitor in combination with nab-paclitaxel and carboplatin/cisplatin.
• No prior history of other malignant tumors.
• Aged between 18 and 75 years.
• Normal baseline (preoperative) clinical and laboratory findings:
• 1.Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without the use of granulocyte colony-stimulating factor (G-CSF) within the previous 14 days
• 2.Platelet count ≥ 100 × 10⁹/L without blood transfusion within the previous 14 days
• 3.Hemoglobin \> 9 g/dL without blood transfusion or erythropoietin use within the previous 14 days
• 4.Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• 5\. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
• 6\. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 60 mL/min
• 7\. Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN
• 8\. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Subjects with TSH outside the normal range may be included if total T3 (or FT3) and FT4 are within normal limits
• 9\. Normal myocardial enzyme profile (minor laboratory abnormalities judged by the investigator to be clinically insignificant are acceptable)
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose of study treatment (Cycle 1, Day 1). If the urine test is indeterminate, a serum test must be performed. Non-childbearing females are defined as those who have been postmenopausal for at least one year or have undergone surgical sterilization or hysterectomy.
• All subjects (male or female) with reproductive potential must agree to use highly effective contraception (annual failure rate \<1%) during treatment and for at least 120 days after the last dose of study drug, or 180 days after the last dose of chemotherapy.
• Adverse events related to neoadjuvant therapy (e.g., bone marrow suppression, thyroiditis, hypothyroidism, hepatitis, nephritis, myocarditis, myositis, etc.) must have been adequately controlled and resolved to grade 0-2 before surgery. Patients assessed by anesthesiology as fit for general anesthesia may be included.
• Patients with pre-existing comorbidities prior to neoadjuvant therapy may also be enrolled if evaluated by anesthesiology and deemed able to tolerate general anesthesia.
• Signed written informed consent.