Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Prior treatment

• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to treatment. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic treatment.
• a. HBV viral load \< 1000 copies/mL (200 IU/mL) prior to first dosing, provided antiviral therapy is administered throughout the study period to prevent viral reactivation
• 2\. Vascular diseases: history of unstable angina, myocardial infarction, transient ischemic attack, or stroke within 6 months prior to enrollment

Other illness

• Diagnosis of another malignant tumor, or the primary lesion at the time of neoadjuvant therapy was not oral cancer.
• History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known history of human immunodeficiency virus (HIV) infection (i.e., positive HIV-1/2 antibody).
• b. Subjects who are anti-HBc(+), HBsAg(-), anti-HBs(-), and HBV-DNA(-) do not require prophylactic antiviral therapy but must undergo close monitoring for viral reactivation.
• Active hepatitis C virus (HCV) infection, defined as positive HCV antibody with detectable HCV-RNA above the lower limit of detection.
• Presence of severe or uncontrolled systemic diseases, including but not limited to:
• 1\. Cardiac disorders: severe arrhythmias (e.g., complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmia, or persistent atrial fibrillation), unstable angina, or congestive heart failure (NYHA class ≥ II)
• 3\. Poorly controlled hypertension: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg
• 4\. Pulmonary diseases: noninfectious pneumonitis requiring corticosteroid treatment within 1 year before first dosing, or active interstitial lung disease
• 5\. Infectious diseases: active infections requiring systemic therapy, or severe uncontrolled infections
• 6\. Active pulmonary tuberculosis
• 7\. Gastrointestinal diseases: clinically active diverticulitis, intra-abdominal abscess, or intestinal obstruction
• 8\. Hepatic disorders: liver cirrhosis, decompensated liver disease, or acute/chronic active hepatitis
• 11\. Psychiatric disorders: severe mental illness that may affect treatment compliance.

Lab values

• Untreated active hepatitis B infection, defined as HBsAg positivity with HBV-DNA levels exceeding the upper limit of normal (ULN) at the study site laboratory. Subjects meeting the following criteria may be enrolled:
• 9\. Uncontrolled diabetes mellitus: fasting blood glucose (FBG) \> 10 mmol/L

Other

• Pregnant or lactating women.
• 10\. Renal dysfunction: urine protein ≥ ++ on routine urinalysis and 24-hour urinary protein \> 1.0 g

• 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.