This study aims to evaluate the effectiveness and safety of endoscopic nasopharyngeal pseudomembrane removal in reducing radiation-induced nasopharyngeal necrosis in patients with recurrent nasopharyngeal carcinoma who have received re-irradiation. This is a prospective, single-arm, multicenter interventional study. Participants with recurrent nasopharyngeal carcinoma who develop pseudomembrane reaction during or after re-irradiation will receive endoscopic pseudomembrane removal. Based on published literature, the 2-year incidence of radiation-induced nasopharyngeal necrosis after re-irradiation is approximately 40%. This study expects to reduce the incidence to 20%. The primary outcome measure is the 2-year incidence of nasopharyngeal necrosis after re-irradiation. Secondary outcome measures include: necrosis-free survival, overall survival, progression-free survival, local regional recurrence-free survival, distant metastasis-free survival, as well as safety and adverse events. A total of 40 participants will be enrolled from multiple hospitals in China.

Study Design: This is a prospective, single-arm, multicenter interventional study without randomization or blinding. The study will be conducted at three hospitals in China: Jiangxi Provincial Cancer Hospital, The Fifth Affiliated Hospital of Sun Yat-sen University, and The First Affiliated Hospital of Nanchang University. A total of 40 participants will be enrolled.

Sample Size Calculation: Based on published literature, the 2-year incidence of radiation-induced nasopharyngeal necrosis after re-irradiation (re-RT) in patients with recurrent nasopharyngeal carcinoma is approximately 40%. This study expects to reduce the incidence to 20%. With a one-sided alpha of 0.05 and power of 80% (beta = 0.20), the calculated sample size is 36 patients. Considering a 10% dropout or loss to follow-up rate, the target enrollment is 40 patients.

Inclusion Criteria (key): Age 18-80 years; ECOG ≤ 2; prior radical radiotherapy with dose ≥ 66Gy; imaging or histopathology confirmed local recurrence and/or retropharyngeal lymph node recurrence with or without cervical lymph node recurrence; re-irradiation with single dose < 2.3Gy and total dose ≥ 50Gy; presence of pseudomembrane reaction on nasopharyngeal mucosa during or after re-irradiation; expected survival > 1 year; induction chemotherapy, immunotherapy, concurrent chemotherapy, adjuvant chemotherapy, or radiotherapy alone are all permitted.

Intervention Procedure: Endoscopic nasopharyngeal pseudomembrane removal will be performed by experienced otolaryngologists. The procedure is carried out in patients with recurrent nasopharyngeal carcinoma who develop pseudomembrane reaction during or after re-irradiation.

Follow-up Schedule: Participants will be followed up every 3 months for 2 years after the intervention. Follow-up assessments include nasopharyngeal endoscopy, imaging studies (MRI or CT), symptom evaluation, and recording of adverse events.

Statistical Methods: The primary outcome (2-year incidence of nasopharyngeal necrosis) will be reported as a proportion with 95% confidence interval. Secondary outcomes including necrosis-free survival, overall survival, progression-free survival, local regional recurrence-free survival, and distant metastasis-free survival will be analyzed using Kaplan-Meier methods. Safety will be assessed by summarizing the type, frequency, and severity of adverse events.

Data Monitoring and Safety: Adverse events will be collected from the time of informed consent through the end of the study follow-up. Serious adverse events will be reported to the ethics committee and regulatory authorities according to local requirements.

Inclusion Criteria:

• Voluntarily sign the informed consent form.
• Age between 18 and 80 years.
• ECOG performance status ≤ 2.
• Prior radical radiotherapy with total dose ≥ 66 Gy.
• Imaging or histopathology confirmed local recurrence and/or retropharyngeal lymph node recurrence, with or without cervical lymph node recurrence.
• Re-irradiation with single dose < 2.3 Gy and total dose ≥ 50 Gy.
• Presence of pseudomembrane reaction on nasopharyngeal mucosa during or after re-irradiation.
• Expected survival > 1 year.
• Induction chemotherapy, immunotherapy, concurrent chemotherapy, adjuvant chemotherapy, or radiotherapy alone are all permitted.

Exclusion Criteria:

• History of other malignancies within the past 5 years, except cured non-melanoma skin cancer or carcinoma in situ of the cervix.
• Severe uncontrolled systemic diseases (e.g., uncontrolled infection, severe cardiovascular disease, uncontrolled diabetes).
• Pregnant or breastfeeding women.
• Known allergy to any equipment or medication used during endoscopy.
• Inability to tolerate endoscopic procedure due to anatomical or medical reasons.
• Concurrent participation in another interventional clinical trial.
• Any condition that, in the investigator's judgment, would interfere with study compliance or outcome assessment.