title: Surrogate endpoints for overall survival in combined chemotherapy and radiotherapy trials in nasopharyngeal carcinoma: Meta-analysis of randomised controlled trials.
abstract: OBJECTIVE
  We used a literature-based meta-analysis to assess whether failure-free survival (FFS) or progression-free survival (PFS) could be reliable surrogate endpoints for overall survival (OS) in trials of combined chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  We identified randomised trials that evaluated combined chemoradiotherapy strategies, and reported FFS or PFS and OS in NPC. We analysed the treatment effects on FFS or PFS, and OS. We used the coefficient of determination (R(2)), and the surrogate threshold effect (STE) to assess the trial-level correlation.
  
  
  RESULTS
  Twenty-one trials (5212 patients), with sixteen treatment-control comparisons for FFS, and nine for PFS, were analysed. FFS was strongly correlated with OS (R(2)=0.88, STE=0.84), as was PFS (R(2)=0.90, STE=0.88). Moreover, FFS and PFS at 3 years were still strongly correlated with 5-year OS (R(2)=0.80, STE=0.83; R(2)=0.85, STE=0.84).
  
  
  CONCLUSIONS
  Both FFS and PFS could be valid surrogate endpoints for OS in trials of combined chemotherapy and radiotherapy for NPC; PFS may be a more acceptable surrogate endpoint compared with FFS.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Wen-Na
authors.initials: WN
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Guan-Qun
authors.initials: GQ
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China. Electronic address: majun2@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D014408:Biomarkers, Tumor
keywords: Chemotherapy; Failure-free survival; Nasopharyngeal carcinoma; Progression-free survival; Radiotherapy; Surrogate endpoint