A Single Arm, Phase II Clinical Study of Low-Dose Radiotherapy Combined With Anti-PD-1 Monoclonal Antibody Immunotherapy as Neoadjuvant Treatment for Surgically Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
Over 60% of head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at a locally advanced stage. While standard treatments involve surgery and chemoradiotherapy, prognosis remains poor, with 50-60% experiencing local recurrence within two years. Neoadjuvant therapy can potentially reduce tumor burden, preserve organs, and lower distant metastasis risk. Despite the KEYNOTE-689 trial showing that adjuvant two-cycle pembrolizumab increased major pathological response to 9.8% in stage III-IVB HNSCC, this result remains insufficient. More effective immunotherapy-based combinations are urgently needed to improve long-term survival after neoadjuvant treatment. Preclinical and clinical evidence indicates that low-dose radiotherapy can activate the tumor immune microenvironment and synergize with immunotherapy. Based on this rationale, the present clinical trial will evaluate a neoadjuvant regimen combining LDRT with two cycles of an anti-PD-1 inhibitor in patients with surgically resectable, locally advanced HNSCC.
• Voluntarily sign and date the informed consent form.
• Untreated, histologically confirmed squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx, or larynx) with CPS ≥1, classified as stage T3-4bN0M0 or T1-4bN1-3M0, corresponding to stage III-IVB according to the AJCC Staging System, 8th Edition.
• Deemed eligible for curative surgery based on surgeon's assessment.
• Age: 18 to 75 years.
• ECOG performance status of 0 or 1.
• Life expectancy greater than 6 months.
• At least one measurable lesion as per RECIST 1.1 criteria.
• Adequate organ function, defined as meeting all the following criteria (without receipt of blood products, colony-stimulating factors, or hematopoietic growth factors within 14 days prior to testing): Hemoglobin ≥ 90 g/L Absolute neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Serum albumin ≥ 28 g/L Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ALT and AST ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min Activated partial thromboplastin time (aPTT) and international normalized ratio (INR) ≤ 1.5 × ULN (patients on a stable dose of anticoagulant therapy such as low molecular weight heparin or warfarin are eligible if INR is within the therapeutic range) Thyroid-stimulating hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels must be evaluated, and patients with normal T3 and T4 levels are eligible.
• Women of childbearing potential must agree to use effective contraception (e.g., intrauterine device, oral contraceptives, or condoms) during the treatment period and for 3 months after the last dose.
• Good compliance with the study protocol.