Individualized Neck Cervical Irradiation Prophylaxis Trial of NPC

Based on the pattern of nasopharyngeal carcinoma cervical lymph node metastasis, which typically follows a sequential downward spread with rare skip metastases and a tendency for ipsilateral neck involvement, and in accordance with the latest international guidelines, we propose the following scientific hypothesis: individualized neck prophylactic irradiation for nasopharyngeal carcinoma based on the superior-to-inferior extent of metastatic lymph nodes is feasible. Specifically: if there is no lymph node metastasis, irradiation need only extend to the lower border of Level II; if there are suspected metastatic lymph nodes, a prophylactic dose of 55-60 Gy should be administered; the investigational arm will only require irradiation extending to 3 cm below the lowest level of metastatic (including suspected) lymph nodes in each neck.This study will prospectively enroll patients with N0-N3 stage nasopharyngeal carcinoma and randomize them to compare individualized neck irradiation based on the vertebral body level of metastatic lymph nodes versus selective upper neck prophylactic irradiation. The primary endpoint is neck recurrence-free survival. Secondary endpoints include overall survival, local recurrence-free survival and other survival data, incidence of acute and late neck radiation-induced injuries, and quality of life, aiming to validate the feasibility of individualized neck irradiation based on metastatic patterns.Photon IMRT and photon plus carbon-ion radiotherapy will serve as stratification factors, enabling further comparison of local control and toxicity between photon-carbon-ion therapy and photon-only (or proton) therapy. This study seeks to protect critical structures such as the thyroid, trachea, esophagus, and neck muscles while maintaining therapeutic efficacy, ultimately improving the quality of life for nasopharyngeal carcinoma patients.

Sex

All

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

1. Age 18-70 years.
2. Pathologically confirmed WHO type I, II, or III nasopharyngeal carcinoma.
3. Staged as T1-4N0-3 M0, Stage I-III according to the UICC/AJCC 9th edition staging system.
4. Absence of distant metastasis confirmed by systemic FDG PET/CT (or whole-body bone scan plus chest CT and abdominal ultrasound).
5. Ability to undergo MRI examination.
6. Adequate major organ function meeting radiotherapy requirements:

   1. Hematopoietic function: Hemoglobin ≥9 g/L, Platelets ≥100×10⁹/L, WBC ≥3.5×10⁹/L, Neutrophils ≥2.0×10⁹/L.
   2. Liver function: ALT and AST \< 2.5 × ULN, Bilirubin \< 1.5 × ULN.
   3. Renal function: Creatinine clearance ≥50 mL/min or serum creatinine within normal range.
   4. Patients with clinical symptoms will be evaluated based on specific manifestations.
7. ECOG performance status 0-1; absence of severe comorbidities (e.g., severe pulmonary hypertension, cardiovascular disease, peripheral vascular disease, severe chronic heart disease) that may preclude radiotherapy. Cardiac function class 1-2 (NYHA classification).
8. Life expectancy ≥12 months.
9. Patients must be informed of the study details and provide written informed consent.

Exclusion Criteria:

1. Pathology not confirming WHO type I, II, or III nasopharyngeal carcinoma.
2. Distant metastasis identified clinically or radiologically before treatment, or presence of skip metastases in cervical lymph nodes.
3. Pregnancy (confirmed by serum or urine β-HCG test) or lactation.
4. Unwillingness to provide informed consent.
5. Prior radiotherapy to the head and neck region.
6. Comorbidities or other factors that may contraindicate photon or carbon-ion therapy.
7. Inability to comply with regular follow-up due to psychological, social, familial, or geographical reasons.
8. Known allergy to chemotherapeutic agents (e.g., cisplatin, docetaxel, gemcitabine) or contrast media used in the study's imaging examinations.
9. Contraindication to contrast-enhanced MRI.
10. Major organ dysfunction, or severe uncontrolled concurrent infection or medical illness (e.g., decompensated cardiac, pulmonary, renal, or hepatic failure).
11. History of immunodeficiency (positive HIV test), other acquired/congenital immunodeficiency disorders, or history of organ/allogeneic bone marrow transplantation.
12. History of other malignancies prior to enrollment (except for basal cell carcinoma of the skin).
13. History of substance or alcohol abuse.
14. Any other condition deemed by the investigator to potentially lead to study discontinuation, including co-morbidities (including psychiatric) requiring concomitant treatment, severely abnormal laboratory values, or familial/social factors compromising patient safety or data integrity.

• RESULTZhu GL, Zhang XM, Yang KB, Tang LL, Ma J. Metastatic patterns of level II-V cervical lymph nodes assessed per vertebral levels in nasopharyngeal carcinoma. Radiother Oncol. 2023 Feb;179:109447. doi: 10.1016/j.radonc.2022.109447. Epub 2022 Dec 19. PMID 36549338
• RESULTLiu Y, Han Y, Liu F, Hu D, Chen Z, Wang P, Li J, Qin J, Jin F, Li Y, Wang J, Yi J. Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial. BMC Cancer. 2023 Aug 3;23(1):724. doi: 10.1186/s12885-023-11212-7. PMID 37537541
• RESULTLiu Y, Yan W, Hu C, Huang X, Wang K, Qu Y, Chen X, Wu R, Zhang Y, Zhang J, Luo J, Li Y, Wang J, Yi J. Optimizing Cervical Target Volume in Patients with Nasopharyngeal Cancer Based On Nodal Drainage Distance. Clin Cancer Res. 2024 May 1;30(9):1801-1810. doi: 10.1158/1078-0432.CCR-23-3274. PMID 38349999
• RESULTWang L, Wu Z, He Q, Li Y, Wang S, Li F, Wang H, Li W, Han Y. Distribution of regional lymph nodes metastasis in 870 cases of nasopharyngeal carcinoma and the suggestions for individualized elective prophylactic neck irradiation with intensity-modulated radiotherapy. Cancer Med. 2024 Feb;13(3):e6723. doi: 10.1002/cam4.6723. Epub 2023 Dec 29. PMID 38156901
• RESULTXie DH, Wu Z, Li WZ, Cheng WQ, Tao YL, Wang L, Lv SW, Lin FF, Cui NJ, Zhao C, Ma J, Huang SM, Lu TX, Han YQ, Su Y. Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary. J Cancer Res Clin Oncol. 2022 Aug;148(8):1931-1942. doi: 10.1007/s00432-022-03974-7. Epub 2022 Apr 29. PMID 35486182
• RESULTWu Z, Qi B, Lin FF, Zhang L, He Q, Li FP, Wang H, Han YQ, Yin WJ. Characteristics of local extension based on tumor distribution in nasopharyngeal carcinoma and proposed clinical target volume delineation. Radiother Oncol. 2023 Jun;183:109595. doi: 10.1016/j.radonc.2023.109595. Epub 2023 Mar 3.