Under Whole-course of Immunotherapy, Gradient Fractionated RT with CCT Versus CFRT with CCT for LANPC Who Achieved PR Post Induction Chemotherapy.

Inclusion criteria

• Histologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
• Tumor staged as III-IVA (AJCC 8th).
• Patients who achieved partial response according to the RECIST criteria on the basis of MRI, PET-CT and endoscopic biopsy after 3 cycles of induction therapy of platinum-based chemotherapy plus immunotherapy.
• Eastern Cooperative Oncology Group performance status ≤1.
• Age: 18-65 years old.
• Adequate organ function:

Adequate marrow function: neutrocyte count≥4×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.

Adequate liver and kidney function: Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 2.5×ULN.; creatinine clearance rate ≥ 60 ml/min or creatinine of no more than 1.5 times the upper normal limit.

• Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion criteria

• Patients who are evaluated as CR or SD or PD after 3 cycles of induction therapy of platinum-based chemotherapy plus PD-1/PD-L1 blockades.
• The laboratory examination value does not meet the relevant standards within 7 days before enrollment.
• The images of PET-CT and enhanced MRI/CT before induction chemotherapy showed necrotic foci in the center of primary tumors or regional lymph nodes.
• The metabolic changes shown by PET-CT images after induction chemotherapy were inconsistent with the changes in the extent of tumor invasion shown by anatomical images such as enhanced MRI/CT.
• The primary and/or cervical metastases of patients have received prior chemotherapy, immunotherapy, targeted therapy, or surgery (except diagnostic treatment).
• Has a known history of hypersensitivity to any components of the PD-1/PD-L1 blockades formulation or other monoclonal antibodies.
• Has a known or suspected history of autoimmune diseases, including dementia and seizures.
• Patients with recurrence, distant metastasis and other malignant tumors.
• Severe heart disease, lung dysfunction, heart function, lung function below grade 3 (including grade 3)
• Patients who underwent anti-PD-1 /PD-L1 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell synergistic stimulation or checkpoint pathway) and anti-angiogenic drugs.
• Complications requiring long-term use of immunosuppressive drugs or systemic or local use of immunosuppressive-dose corticosteroids.
• HIV positive; HBsAg positive and HBV DNA copy number positive (quantitative detection ≥ 1000 cps/ml); chronic hepatitis C with blood screening positive (HCV antibody positive).
• Has a known history of allergic reactions to the drugs in the study (gemcitabine, cisplatin, docetaxel, abraxane, paclitaxel ).
• Has a known history of active TB (bacillus tuberculosis) within 1 year; anti-TB treatment is ongoing or within 1 year prior to screening.
• Has received a live vaccine; or a systematic glucocorticoid therapy ; or any anti-infective vaccine (e.g. influenza vaccine, varicella vaccine, etc.) ; any Chinese anti-tumor herbs within 4 weeks prior to enrollment.
• Pregnancy or breastfeeding.
• Other patients who were considered unsuitable by the treating physicians.