Individualized Versus Standard Neck Prophylactic Irradiation in Nasopharyngeal Carcinoma: A Non-inferiority, Phase III, Multicenter, Prospective, Randomized Controlled Trial
Based on the pattern of nasopharyngeal carcinoma cervical lymph node metastasis, which typically follows a sequential downward spread with rare skip metastases and a tendency for ipsilateral neck involvement, and in accordance with the latest international guidelines, we propose the following scientific hypothesis: individualized neck prophylactic irradiation for nasopharyngeal carcinoma based on the superior-to-inferior extent of metastatic lymph nodes is feasible. Specifically: if there is no lymph node metastasis, irradiation need only extend to the lower border of Level II; if there are suspected metastatic lymph nodes, a prophylactic dose of 55-60 Gy should be administered; the investigational arm will only require irradiation extending to 3 cm below the lowest level of metastatic (including suspected) lymph nodes in each neck.This study will prospectively enroll patients with N0-N3 stage nasopharyngeal carcinoma and randomize them to compare individualized neck irradiation based on the vertebral body level of metastatic lymph nodes versus selective upper neck prophylactic irradiation. The primary endpoint is neck recurrence-free survival. Secondary endpoints include overall survival, local recurrence-free survival and other survival data, incidence of acute and late neck radiation-induced injuries, and quality of life, aiming to validate the feasibility of individualized neck irradiation based on metastatic patterns.Photon IMRT and photon plus carbon-ion radiotherapy will serve as stratification factors, enabling further comparison of local control and toxicity between photon-carbon-ion therapy and photon-only (or proton) therapy. This study seeks to protect critical structures such as the thyroid, trachea, esophagus, and neck muscles while maintaining therapeutic efficacy, ultimately improving the quality of life for nasopharyngeal carcinoma patients.
• Age 18-70 years.
• Pathologically confirmed WHO type I, II, or III nasopharyngeal carcinoma.
• Staged as T1-4N0-3 M0, Stage I-III according to the UICC/AJCC 9th edition staging system.
• Absence of distant metastasis confirmed by systemic FDG PET/CT (or whole-body bone scan plus chest CT and abdominal ultrasound).
• Ability to undergo MRI examination.
• Adequate major organ function meeting radiotherapy requirements:
‣ Hematopoietic function: Hemoglobin ≥9 g/L, Platelets ≥100×10⁹/L, WBC ≥3.5×10⁹/L, Neutrophils ≥2.0×10⁹/L.
⁃ Liver function: ALT and AST \< 2.5 × ULN, Bilirubin \< 1.5 × ULN.
⁃ Renal function: Creatinine clearance ≥50 mL/min or serum creatinine within normal range.
⁃ Patients with clinical symptoms will be evaluated based on specific manifestations.
• ECOG performance status 0-1; absence of severe comorbidities (e.g., severe pulmonary hypertension, cardiovascular disease, peripheral vascular disease, severe chronic heart disease) that may preclude radiotherapy. Cardiac function class 1-2 (NYHA classification).
• Life expectancy ≥12 months.
• Patients must be informed of the study details and provide written informed consent.