title: Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment.
abstract: To better manage patients with de novo metastatic NPC (mNPC) including easily identifying individuals' survival outcomes and accurately choosing the most suitable treatment.
  
  
  
  Three independent cohorts of mNPC patients (a training set of n = 462, an internal prospective validation set of n = 272 and an external prospective validation set of n = 243) were studied. The radiological characteristics of distant metastases, including number of metastatic locations, number of metastatic lesions and size of metastatic lesions, were carefully defined based on imaging data. These three factors and other potential prognostic factors were comprehensively analysed and were further integrated into new subdivisions of stage M1 using a Cox proportional hazards model.
  
  
  
  We successfully subdivided the M1 stage into three categories: M1a, oligo metastasis without liver involvement; M1b, multiple metastases without liver involvement; and M1c, liver involvement irrespective of metastatic lesions. The 3-year overall survival ranged from 54.5% to 72.8%, from 34.3% to 41.6% and from 22.6.0%-23.6% for M1a, M1b and M1c, respectively (P < 0.001). Systemic chemotherapy combined with radical loco-regional radiotherapy may benefit patients in M1a and M1b, not in M1c. Further aggressive treatment of metastatic lesions based on systemic chemotherapy and definitive loco-regional radiotherapy showed no survival benefit, even for patients in M1a (P > 0.05).
  
  
  
  The subdividing of M1 provided promising prognostic value and could aid clinicians in choosing the most suitable treatment for de novo mNPC patients.
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: You
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital, 283 Tongzipo Road, Changsha 410000, PR China.
authors.forename: Huai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha 410008, PR China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, 78 Hengzhigang, Guangzhou 510095, PR China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Xie
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha 410008, PR China.
authors.forename: Zhi-Hai
authors.initials: ZH
authors.lastname: Xie
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Clinical Trials Center, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China.
authors.forename: Ji-Bin
authors.initials: JB
authors.lastname: Li
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Rou
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: You-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Hua
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: Department of Radiation Oncology, Cancer Center of Guangzhou Medical University, 78 Hengzhigang, Guangzhou 510095, PR China.
authors.forename: Dong-Ping
authors.initials: DP
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Hunan Cancer Hospital, 283 Tongzipo Road, Changsha 410000, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Radiation Oncology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha 410008, PR China.
authors.forename: Liang-Fang
authors.initials: LF
authors.lastname: Shen
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Clinical Trials Center, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, PR China; Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: chmingy@mail.sysu.edu.cn.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
mesh_terms: D002277:Carcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies
keywords: Chemotherapy; De novo; Distant metastasis; Nasopharyngeal carcinoma; Radiotherapy; Subdivisions