Radscopal Radiotherapy Plus Immunotherapy for Chemotherapy-Ineligible Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer: A Single-Center, Open-Label, Phase II Study

Inclusion criteria

• 1. Age 18-80 years.
• 2. Histologically or cytologically confirmed de novo metastatic nasopharyngeal carcinoma (TxNxM1 according to AJCC 9th edition), with ≤10 measurable metastatic lesions.
• 3. At least one measurable nasopharyngeal lesion suitable for low-dose radiotherapy and at least one distant metastatic lesion suitable for stereotactic body radiotherapy.
• 4. ECOG performance status 0-2.
• 5. PD-L1 combined positive score (CPS) ≥1.
• 6. Chemotherapy-ineligible, including patients medically unsuitable for platinum-based chemotherapy or patients who refuse standard platinum-based chemotherapy after being fully informed.
• 7. Life expectancy ≥6 months.
• 8. Adequate organ function, including ANC ≥1.0 × 10^9/L, platelets ≥75 × 10^9/L, hemoglobin ≥80 g/L, ALT/AST ≤3 × ULN, bilirubin ≤2 × ULN, creatinine clearance ≥30 mL/min, and LVEF ≥45% or normal echocardiography.
• 9. No major surgery within 1 month before enrollment.
• 10. No immunosuppressive or immunomodulatory therapy within 1 month before immune checkpoint inhibitor treatment.
• 11. Written informed consent and ability to comply with study procedures and follow-up.

Exclusion criteria

• 1. Age <18 years.
• 2. >10 metastatic lesions, meningeal metastasis, spinal cord compression, or lesions unsuitable for safe stereotactic body radiotherapy.
• 3. Other malignancy within 5 years, except cured basal cell carcinoma, squamous cell carcinoma of the skin, papillary thyroid carcinoma, or cervical carcinoma in situ.
• 4. Prior systemic immune checkpoint inhibitor therapy or prior nasopharyngeal radiotherapy.
• 5. Active hepatitis B infection, defined as HBsAg positivity with HBV DNA >200 IU/mL or >1000 copies/mL.
• 6. Positive hepatitis C virus antibody.
• 7. Active, known, or suspected autoimmune disease, except type 1 diabetes, hypothyroidism requiring only hormone replacement, or skin disorders not requiring systemic treatment.
• 8. Systemic corticosteroids equivalent to >10 mg prednisone daily or other immunosuppressive therapy within 28 days before informed consent, except low-dose, inhaled, or topical corticosteroids.
• 9. Active tuberculosis, active tuberculosis within the previous year, or prior active tuberculosis without documented adequate anti-tuberculosis treatment.
• 10. History of interstitial lung disease.
• 11. Uncontrolled diabetes mellitus (fasting blood glucose >13.9 mmol/L).
• 12. Live vaccine within 30 days before informed consent or planned live vaccination.
• 13. Known allergy to macromolecular protein preparations or to any component of sintilimab or ipilimumab.
• 14. HIV infection.
• 15. Any condition that may affect participant safety or compliance, including uncontrolled cardiovascular disease, active infection requiring systemic treatment, psychiatric illness, severe cognitive impairment, suicidal tendency, or relevant psychological, family, or social factors.