title: Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma.
abstract: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC.
  
  
  
  Retrospective cohort study.
  
  
  
  We examined 101 patients with primary NPC who underwent pretreatment18F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features.
  
  
  
  The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001).
  
  
  
  Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity.
  
  
  
  4 Laryngoscope, 127:E22-E28, 2017.
authors.affiliation: Department of Nuclear Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.|Molecular Imaging Center and Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Sheng-Chieh
authors.initials: SC
authors.lastname: Chan
authors.affiliation: Department of Otorhinolaryngology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Hua Dean
authors.initials: YD
authors.lastname: Fang
authors.affiliation: Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.affiliation: Department of Diagnostic Radiology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Department of Otorhinolaryngology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.affiliation: Molecular Imaging Center and Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.|Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
mesh_terms: D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy / Q000821:virology*; D003131:Combined Modality Therapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy / Q000821:virology*; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography; D011379:Prognosis; D011857:Radiographic Image Interpretation, Computer-Assisted; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Epstein-Barr virus; F-18 fluorodeoxyglucose; Nasopharyngeal carcinoma; heterogeneity; positron emission tomography; prognosis; risk stratification; texture features