title: Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma.
abstract: Plasma Epstein-Barr virus (EBV) DNA titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (NPC). However, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. We recruited 260 evaluable patients with non-metastatic NPC treated with radical intensity-modulated radiation therapy (IMRT) with or without adjunct chemotherapy. Plasma EBV DNA titers at baseline and then 8 weeks and 6 months after IMRT were measured. Cox regression models were employed to identify interaction between post-IMRT 8th week and 6th month undetectable titers and 3-year survival endpoints. Concordance indices (Ct) from time-dependent receiver-operating characteristics (TDROC) were compared between patients with post-IMRT undetectable and those with detectable titers. After a median follow-up duration of 3.4 years (range 1.4-4.6 years), patients with post-IMRT 8th week and 6th month undetectable plasma EBV DNA titers enjoyed longer 3-year survival endpoints than those who had detectable titers at the same time points. Post-IMRT 8th week, and more significantly, post-IMRT 6th month undetectable plasma EBV DNA were the only significant prognostic factors of 3-year survival endpoints. Ct values for all 3-year survival endpoints for both post-IMRT 8th week and 6th month undetectable plasma EBV DNA were significantly higher in those with stage IVA-IVB diseases compared to stage I-III counterparts. Early post-IMRT undetectable plasma EBV DNA titers were prognostic of 3-year survival endpoints in patients with non-metastatic NPC. Intensified treatment should be further explored for patients with persistently detectable titers after IMRT.
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Victor Ho-Fun
authors.initials: VH
authors.lastname: Lee
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Dora Lai-Wan
authors.initials: DL
authors.lastname: Kwong
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: To-Wai
authors.initials: TW
authors.lastname: Leung
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Cheuk-Wai
authors.initials: CW
authors.lastname: Choi
authors.affiliation: Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lai
authors.affiliation: Department of Radiation Oncology, University of Southern California, Los Angeles, California, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Ng
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Ka-On
authors.initials: KO
authors.lastname: Lam
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Sherry Chor-Yi
authors.initials: SC
authors.lastname: Ng
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Chun-Kin
authors.initials: CK
authors.lastname: Sze
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Tong
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Patty Pui-Ying
authors.initials: PP
authors.lastname: Ho
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Chan
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Lai-San
authors.initials: LS
authors.lastname: Wong
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Dennis Kwok-Chuen
authors.initials: DK
authors.lastname: Leung
authors.affiliation: Department of Clinical Oncology, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Sum-Yin
authors.initials: SY
authors.lastname: Chan
authors.affiliation: Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Pek-Lan
authors.initials: PL
authors.lastname: Khong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000097:blood / Q000532:radiotherapy* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000532:radiotherapy* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000532:radiotherapy* / Q000821:virology; D011379:Prognosis; D012372:ROC Curve; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016019:Survival Analysis; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: intensity-modulated radiation therapy; nasopharyngeal carcinoma; non-metastatic; plasma EBV DNA; prognostic factors