Individualized neck irradiation for nasopharyngeal carcinoma

Individualized Versus Standard Neck Prophylactic Irradiation in Nasopharyngeal Carcinoma: A Non-inferiority, Phase III, Multicenter, Prospective, Randomized Controlled Trial

This trial will test whether tailoring how far the neck is radiated based on each patient's lymph node spread works as well as standard broader neck radiation for adults with newly diagnosed, non-metastatic nasopharyngeal carcinoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 462 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: radiation, chemotherapy
• Locations: 6 sites (Shanghai, Shanghai Municipality and 5 other locations)
• Trial ID: NCT07303023 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective, randomized, open‑label phase III non‑inferiority trial enrolling 462 patients with newly diagnosed, non‑metastatic nasopharyngeal carcinoma (T1‑4N0‑3M0). Patients are randomized to an individualized neck irradiation arm—where prophylactic coverage extends to 3 cm below the lowest involved or suspected lymph node—versus a standard bilateral upper‑plus‑lower neck prophylactic irradiation arm. Radiotherapy planning follows the 2024 international contouring guidelines and stratifies by photon IMRT alone versus photon IMRT combined with carbon‑ion radiotherapy, with prescribed dose levels specified for gross tumor and elective volumes. The planned accrual is three years with three years of post‑treatment follow‑up to compare regional control and safety between arms.

Who should consider this trial

Good fit: Adults 18–70 with newly diagnosed, non‑metastatic WHO type I–III nasopharyngeal carcinoma staged T1–4N0–3M0 (UICC/AJCC 9th ed.), ECOG 0–1, adequate organ function, and ability to undergo MRI and required staging scans.

Not a fit: Patients with distant metastases, poor performance status, severe comorbidities that preclude radiotherapy, or with tumor/lymph node patterns requiring comprehensive lower‑neck irradiation are unlikely to benefit from the individualized approach.

Why it matters

Potential benefit: If successful, this approach could reduce radiation exposure to the lower neck and thereby lower long‑term side effects like fibrosis and dry mouth while maintaining the same cancer control.

How similar studies have performed: Retrospective series and small prospective cohorts have suggested that limited or selective elective neck irradiation can preserve regional control in selected NPC patients, but large phase III evidence has been limited until now.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality and 5 other locations

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Eye, Ear, Nose and Throat Hospital of Fudan University — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Not_yet_recruiting)
• Sichuan Cancer Hospital & Institute — Chengdu, China (Not_yet_recruiting)
• Chongqing Cancer Hospital — Chongqing, China (Not_yet_recruiting)
• Shanghai Proton and Heavy Ion Center — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Xiyin Guan, MD. PhD.

Conditions Nasopharyngeal Carcinoma; IMRT; carbon ion radiotherapy; Prophylactic Neck Irradiation