title: The impact of the cumulative dose of cisplatin during concurrent chemoradiotherapy on the clinical outcomes of patients with advanced-stage nasopharyngeal carcinoma in an era of intensity-modulated radiotherapy.
abstract: BACKGROUND
  The impact of cumulative dose of cisplatin on clinical outcomes of nasopharyngeal carcinoma (NPC) patients who received intensity-modulated radiotherapy (IMRT) was evaluated.
  
  
  METHODS
  This study included 491 consecutive patients with histologically confirmed NPC who were treated with concurrent chemoradiotherapy with IMRT. The patients were divided into three groups: low- (cumulative dose≤100 mg/m2), medium- (cumulative dose>100 mg/m2 and ≤200 mg/m2), and high- (cumulative dose>200 mg/m2) dose groups. Subgroups of patients included pre-treatment levels of Epstein-Barr Virus DNA (EBV DNA)<4000 copies/ml and pre-treatment EBV DNA≥4000 copies/ml. To test for independent significance, the Kaplan-Meier with the log-rank test and the Cox proportional hazards model were used.
  
  
  RESULTS
  The 5-year overall survival (OS) rates of the low-, medium-, and high-dose groups were 64.1%, 91.1%, and 89.4%, respectively (P=0.002). Based on multivariate analysis, patients who were in the medium- and high-dose groups had compared with the low-dose group, with an odds ratio of 0.135 (95% CI 0.045-0.405, P<0.001) and 0.225 (95% CI 0.069-0.734, P=0.013), respectively. For the low-risk patients, the cumulative dose of cisplatin significantly associated with a lower OS (P<0.001). The medium-dose group had reduced odds of death compared with the low-dose group, with an odds ratio of 0.062 (95% CI 0.001-0.347, P=0.002), according to multivariate analysis.
  
  
  CONCLUSIONS
  The cumulative dose of cisplatin is associated with OS and distant metastasis-free survival (DMFS) among NPC patients who received IMRT.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. guoshsh@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. guoshsh@sysucc.org.cn.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. tanglq@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. tanglq@sysucc.org.cn.
authors.forename: Lin-Quan
authors.initials: LQ
authors.lastname: Tang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. zhanglu@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. zhanglu@sysucc.org.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. chenqy@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. chenqy@sysucc.org.cn.
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. liult@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. liult@sysucc.org.cn.
authors.forename: Li-Ting
authors.initials: LT
authors.lastname: Liu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. guoling@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. guoling@sysucc.org.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. mohy@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. mohy@sysucc.org.cn.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Mo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. luodh@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. luodh@sysucc.org.cn.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Luo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. huangpy@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. huangpy@sysucc.org.cn.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. xiangyq@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. xiangyq@sysucc.org.cn.
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Xiang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. sunrui@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. sunrui@sysucc.org.cn.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. chenmy@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. chenmy@sysucc.org.cn.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. wanglin@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. wanglin@sysucc.org.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. lvxing@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. lvxing@sysucc.org.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Lv
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. zhaochong@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. zhaochong@sysucc.org.cn.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. guoxiang@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. guoxiang@sysucc.org.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. caokj@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. caokj@sysucc.org.cn.
authors.forename: Ka-Jia
authors.initials: KJ
authors.lastname: Cao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. qiancn@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. qiancn@sysucc.org.cn.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. zengmsh@sysucc.org.cn.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. beijinxin@sysucc.org.cn.
authors.forename: Jin-Xin
authors.initials: JX
authors.lastname: Bei
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. hongmh@sysucc.org.cn.|Good Clinical Practice Center, Sun Yat-sen University Cancer Center, Guangzhou, China. hongmh@sysucc.org.cn.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Hong
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. shaojy@sysucc.org.cn.|Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China. shaojy@sysucc.org.cn.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. sunying@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. sunying@sysucc.org.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. majun@sysucc.org.cn.|Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. majun@sysucc.org.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. maihq@sysucc.org.cn.|Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, P. R. China. maihq@sysucc.org.cn.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002277:Carcinoma; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D016016:Proportional Hazards Models; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin