Overview

Patients with stage II-III (AJCC8th) nasopharyngeal carcinoma have high local control in the IMRT era. More and more survivors have to suffer from late radiation-induced toxicities. A previous study showed inferior local control rate but lower late toxicities if radiation dose to primary site was reduced to 60Gy for patients who achieved partital or complete response to induction chemotherapy. Considering that neoadjuvant chemotherapy and immunotherapy has the potential to increase the response rate and long-term survival, the investigators try to reduce the radiation dose to primary site for patients after immunochemotherapy. Per the protocol, the investigators include participants with stage II-III (AJCC8th) except T2N0M0 and administer 3 courses of neoadjuvant gecitabine plus cisplatin and Toripalimab. If primary tumor regresses over 75%, it will receive de-escalted radiotherapy with 60Gy and participants will receive two cycles of cisplatin and Toripalimab during the radiotherapy course. Or else, participants will receive conventional radiotherapy and concurrent chemotherapy with cisplatin as usual. This study aims to explore the 3-year local control rate and toxicities of de-escalted radiotherapy.

Eligibility

Inclusion Criteria:

1. Pathologically confirmed nasopharyngeal carcinoma, patients who have not received anti-cancer therapy;
2. ECOG performance status score (PS score) 0 or 1.
3. 18-70 years old.
4. Exclude stage II-III except T2N0M0 (AJCC version 8).
5. Neutrophil count ≥ 1.5 × 10 9/L, hemoglobin ≥ 90 g/L and platelet count ≥ 100 × 10 9/L.
6. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN), bilirubin ≤ 1.5 times ULN; Creatinine clearance ≥ 60 ml/min
7. Patients must sign an informed consent form and must be willing and able to comply with the visits, treatment plan, laboratory tests, and other requirements specified in the study protocol.

Exclusion Criteria:

Patients will be excluded from the study, if any of the following criteria is met:

1. Age > 70 years or < 18 years.
2. HBsAg positive and HBV DNA > 1 × 10^3 copies/ml
3. HCV antibody positive.
4. Active, known or suspected autoimmune diseases; Subjects with type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and skin conditions not requiring systemic therapy (eg, vitiligo, psoriasis, or alopecia) were eligible.
5. History of interstitial lung disease;
6. Receiving systemic sex hormones or other immunosuppressive therapy at equivalent doses > 10 mg prednisone/day within 28 days prior to signing informed consent; Subjects with systemic sex hormone doses ≤ 10 mg prednisone/day or inhaled/topical corticosteroids were eligible.
7. Received or about to receive live vaccines within 30 days before signing the informed consent form;
8. Pregnant or lactating women;
9. Other malignancies within 5 years, except carcinoma in situ, adequately treated non-melanoma skin cancer and papillary thyroid cancer;
10. Known previous hypersensitivity to macromolecular protein preparations, or to any component of terreplumab;
11. Human immunodeficiency virus (HIV) infection.
12. Other conditions that may affect the safety of subjects or trial compliance as judged by the investigator, including symptomatic heart failure, unstable angina pectoris, myocardial infarction, active infection requiring systemic treatment, mental illness or family and social factors;