title: The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma.
abstract: OBJECTIVE
  To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC).
  
  
  METHODS
  In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).
  
  
  RESULTS
  EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020).
  
  
  CONCLUSIONS
  Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.
authors.affiliation: Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Good Clinical Practice Center, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
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; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: maihq@sysucc.org.cn.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Mai
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000532:radiotherapy / Q000821:virology; D020360:Neoadjuvant Therapy; D011379:Prognosis; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D002945:Cisplatin; D005472:Fluorouracil