Reducing High Risk Primary Tumor Clinical Target Volumes (CTVp1) in Non-metastatic Nasopharyngeal Carcinoma

This phase 3, multicenter,randomized controlled clinical trial recruits patients with newly-diagnosed non-metastatic nasopharyngeal carcinoma patients treated with IMRT. The intervention is delineating high risk primary tumor clinical target volumes (CTVp1) as GTV+5mm or GTV+5mm+whole nasopharynx. The objective is to compare the long-term local control, survival rate, acute and late radiation related toxicities between the two groups.

Inclusion criteria

• histologic confirmation of nonkeratinizing nasopharyngeal carcinoma(WHO II-III);
• newly diagnosed stage I to IVa according to the American Joint Committee on Cancer-Union for International Cancer Control 8th edition stage-classification system
• nasopharyngeal mass confined to one side of nasopharynx and did not exceed the midline(the line between the nasal septum and the midpoint of spinal cord/medulla) detected by electronic nasopharyngoscope (ENS) and magnetic resonance imaging (MRI). Pathological biopsy was recommended if it was unclear whether tumor invaded the contralateral side radiographically.
• planned to receive curative IMRT, Chemotherapy drugs should be administered according to Chinese Society of Clinical Oncology (CSCO) guidelines depending on the TNM stage;(T1N0: No chemotherapy required;T2N0：No chemotherapy or concurrent cisplatin chemoradiotherapy if there are adverse prognostic indicators such as Epstein-Barr virus (EBV) DNA>4000 copies，node >3cm or with extranodal extension;T1-2N1: concurrent cisplatin chemoradiotherapy;T3N0: concurrent cisplatin chemoradiotherapy; stage III-Iva: platinum-based neoadjuvant chemotherapy+ concurrent cisplatin chemoradiotherapy+/-metronomic capecitabine therapy )
• no previous treatment for cancer；
• a Karnofsky performance-status score of at least 70 (on a scale from 0 to 100, with lower scores indicating greater disability);
• between 18 and 70 years old;
• adequate hematologic, renal, and hepatic function: Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;Adequate liver function: ALT and AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;Adequate renal function: BUN and CRE ≤ 1.5×ULN , endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
• Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion criteria

• receipt of treatment with palliative intent;
• receipt of previous treatment (radiotherapy, chemotherapy, or surgery [except diagnostic procedures]) to the nasopharynx;
• had disease progress after neoadjuvant chemotherapy in local advantage NPC
• presence of distant metastasis;
• Keratinized squamous cell carcinoma or basal cell like squamous cell carcinoma;
• Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
• Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
• lactation or pregnancy;
• Any other condition including Mental disorder,drug or alcohol addition;do not have full capacity for civil acts.