title: Development of a ten-signature classifier using a support vector machine integrated approach to subdivide the M1 stage into M1a and M1b stages of nasopharyngeal carcinoma with synchronous metastases to better predict patients' survival.
abstract: The aim of this study was to develop a prognostic classifier and subdivided the M1 stage for nasopharyngeal carcinoma patients with synchronous metastases (mNPC). A retrospective cohort of 347 mNPC patients was recruited between January 2000 and December 2010. Thirty hematological markers and 11 clinical characteristics were collected, and the association of these factors with overall survival (OS) was evaluated. Advanced machine learning schemes of a support vector machine (SVM) were used to select a subset of highly informative factors and to construct a prognostic model (mNPC-SVM). The mNPC-SVM classifier identified ten informative variables, including three clinical indexes and seven hematological markers. The median survival time for low-risk patients (M1a) as identified by the mNPC-SVM classifier was 38.0 months, and survival time was dramatically reduced to 13.8 months for high-risk patients (M1b) (P < 0.001). Multivariate adjustment using prognostic factors revealed that the mNPC-SVM classifier remained a powerful predictor of OS (M1a vs. M1b, hazard ratio, 3.45; 95% CI, 2.59 to 4.60, P < 0.001). Moreover, combination treatment of systemic chemotherapy and loco-regional radiotherapy was associated with significantly better survival outcomes than chemotherapy alone (the 5-year OS, 47.0% vs. 10.0%, P < 0.001) in the M1a subgroup but not in the M1b subgroup (12.0% vs. 3.0%, P = 0.101). These findings were validated by a separate cohort. In conclusion, the newly developed mNPC-SVM classifier led to more precise risk definitions that offer a promising subdivision of the M1 stage and individualized selection for future therapeutic regimens in mNPC patients.
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Department of Cancer Prevention, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Rou
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: You
authors.affiliation: Department of Ultrasonography, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pei
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Meng-Xia
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Tong-Min
authors.initials: TM
authors.lastname: Wang
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Luo
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Hua
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Lin-Quan
authors.initials: LQ
authors.lastname: Tang
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Mo
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Department of Clinical Trials Center, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.affiliation: School of Computer and Engineering, South China University of Technology, Guangzhou, P. R. China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Cai
authors.affiliation: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009303:Nasopharyngeal Neoplasms / Q000145:classification / Q000401:mortality* / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000145:classification / Q000401:mortality* / Q000556:secondary; D011379:Prognosis; D012189:Retrospective Studies; D060388:Support Vector Machine; D015996:Survival Rate
keywords: nasopharyngeal carcinoma; prognosis; support vector machine; synchronous metastases; therapy