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.

This study is a multicenter, prospective, non-inferiority, open-label, phase III randomized controlled clinical trial. A total of 462 patients will be enrolled, with an anticipated accrual period of three years and a follow-up period of three years post-enrollment.

Eligible patients will have newly diagnosed, non-metastatic nasopharyngeal carcinoma, staged as T1-4N0-3M0, Stage I-III according to the UICC/AJCC 9th edition staging system. After confirmation of the radiotherapy technique, patients will be randomized. Patients in the investigational arm will receive bilateral upper neck irradiation covering at least Level II. If cervical lymph nodes are positive, the clinical target volume (CTV) will extend to 3 cm below the lowest level of metastatic (including suspected) lymph nodes. Patients in the control arm will receive bilateral upper neck irradiation; if upper neck nodes are positive, prophylactic irradiation of the lower neck will be performed. Primary tumor and nodal CTV delineation for both arms will adhere to the 2024 international contouring guidelines for nasopharyngeal carcinoma.

Photon IMRT alone or photon IMRT plus carbon-ion radiotherapy will serve as stratification factors. The prescribed doses for photon IMRT alone are as follows: GTVp and GTVn: 66-70.4 Gy in 30-33 fractions; high-risk CTV1: 60 Gy in 30-33 fractions; low-risk CTV2: 50 Gy in 30-33 fractions. For the combined photon IMRT and carbon-ion radiotherapy arm, the prescription doses are: Photon IMRT - GTVp and GTVn: 55 Gy in 25 fractions; high-risk CTV1: 55 Gy in 25 fractions; low-risk CTV2: 50 Gy in 25 fractions. Carbon-ion boost - GTVp and GTVn: 15-18 Gy (RBE) in 6 fractions.

If indicated, patients will receive induction chemotherapy with the GP regimen (Gemcitabine 1000 mg/m² on Day 1 and Day 8, plus Cisplatin 75 mg/m² divided over three days) for 2-3 cycles. Concurrent chemotherapy, if administered, will consist of Cisplatin 80 mg/m² divided over three days, given every 3 weeks for 2 cycles.

Tumor response will be assessed by EBV-DNA levels and MRI at the end of induction chemotherapy, at the end of concurrent chemoradiotherapy, and three months after treatment completion. Follow-up visits will be scheduled every three months for the first two years post-treatment. Subsequent follow-up will be conducted as per protocol. Quality of life questionnaires, as specified by the study, will be completed before treatment, after treatment completion, and during the follow-up period.

Inclusion Criteria:

1. Age 18-70 years.

2. Pathologically confirmed WHO type I, II, or III nasopharyngeal carcinoma.

3. Staged as T1-4N0-3 M0, Stage I-III according to the UICC/AJCC 9th edition staging system.

4. Absence of distant metastasis confirmed by systemic FDG PET/CT (or whole-body bone scan plus chest CT and abdominal ultrasound).

5. Ability to undergo MRI examination.

6. Adequate major organ function meeting radiotherapy requirements:

   1. Hematopoietic function: Hemoglobin ≥9 g/L, Platelets ≥100×10⁹/L, WBC ≥3.5×10⁹/L, Neutrophils ≥2.0×10⁹/L.
   2. Liver function: ALT and AST < 2.5 × ULN, Bilirubin < 1.5 × ULN.
   3. Renal function: Creatinine clearance ≥50 mL/min or serum creatinine within normal range.
   4. Patients with clinical symptoms will be evaluated based on specific manifestations.

7. 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).

8. Life expectancy ≥12 months.

9. Patients must be informed of the study details and provide written informed consent.

Exclusion Criteria:

1. Pathology not confirming WHO type I, II, or III nasopharyngeal carcinoma.
2. Distant metastasis identified clinically or radiologically before treatment, or presence of skip metastases in cervical lymph nodes.
3. Pregnancy (confirmed by serum or urine β-HCG test) or lactation.
4. Unwillingness to provide informed consent.
5. Prior radiotherapy to the head and neck region.
6. Comorbidities or other factors that may contraindicate photon or carbon-ion therapy.
7. Inability to comply with regular follow-up due to psychological, social, familial, or geographical reasons.
8. Known allergy to chemotherapeutic agents (e.g., cisplatin, docetaxel, gemcitabine) or contrast media used in the study's imaging examinations.
9. Contraindication to contrast-enhanced MRI.
10. Major organ dysfunction, or severe uncontrolled concurrent infection or medical illness (e.g., decompensated cardiac, pulmonary, renal, or hepatic failure).
11. History of immunodeficiency (positive HIV test), other acquired/congenital immunodeficiency disorders, or history of organ/allogeneic bone marrow transplantation.
12. History of other malignancies prior to enrollment (except for basal cell carcinoma of the skin).
13. History of substance or alcohol abuse.
14. Any other condition deemed by the investigator to potentially lead to study discontinuation, including co-morbidities (including psychiatric) requiring concomitant treatment, severely abnormal laboratory values, or familial/social factors compromising patient safety or data integrity.