title: Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.
abstract: BACKGROUND
  The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era.
  
  
  METHODS
  We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease.
  
  
  RESULTS
  The incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994).
  
  
  CONCLUSIONS
  In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.
authors.affiliation: Department of Radiation oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Department of Radiation oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Radiation oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Radiation oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Lin
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Mai
authors.affiliation: Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Shao
authors.affiliation: Imaging Diagnosis and Interventional Center, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Radiation oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D002277:Carcinoma; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000532:radiotherapy*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology; D009367:Neoplasm Staging; D010614:Pharynx / Q000473:pathology*; D011379:Prognosis; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies