This is an open-label, multi-center, phase II trial to evaluate the safety and efficacy of postponing or omitting re-irradiation after systemic therapy with tislelizumab and chemotherapy in patients with unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. Patients who did not respond to or progressed on another ICI are allowed to receive tislelizumab rechallenge as a subgroup.

High dose reirradiation is usually recommended for unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. However, it potentially adds to the RT-related severe toxicities and deaths. This trial aims to investigate the feasibility of postponing or even omitting re-irradiation based on effective first-line systemic therapy with tislelizumab and chemotherapy. For patients that progressed after exposure to another PD-1 antibody,tislelizumab rechallenge is accepted as a second subgroup.In this trial, all patients will receive chemotherapy (on doctors' recommendation) and PD-1 antibody (tislelizumab 200mg every three weeks). Patients with no response to the systemic therapy will receive salvage low dose re-irradiation delivered by SBRT, while those who showed complete or partial response will continue maintenance therapy until progression, death or intolerable toxicity, and reirradiation will be postponed or omitted.

Inclusion Criteria:

1. Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment;
2. Not suitable for surgery;
3. Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery.
4. ECOG score 0-1;
5. No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
6. No contraindications to immunotherapy or chemoradiotherapy;
7. Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
8. Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
9. Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
10. Take effective contraceptions during and two months after treatment;
11. Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

1. Have local necrosis in recurrent lesions, estimated with bleeding risk;
2. Unexplained fever > 38.5 ℃, except for tumor fever;
3. Treated with ≥ 5 days antibiotics one month before enrollment;
4. Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);
5. Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;
6. Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
7. Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
8. Have known allergy to large molecule protein products or any compound of study therapy;
9. Pregnant or breastfeeding;
10. Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
11. Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.