title: Validation that metabolic tumor volume predicts outcome in head-and-neck cancer.
abstract: OBJECTIVE
  We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment (18)F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16(INK4a) status as a surrogate marker for human papillomavirus (HPV).
  
  
  METHODS
  The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV(max)) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV.
  
  
  RESULTS
  Similarly to our prior findings, an increase in total MTV of 17 cm(3) (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV(max) was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16(INK4a)-positive oropharyngeal cancer.
  
  
  CONCLUSIONS
  This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Tang
authors.forename: James D
authors.initials: JD
authors.lastname: Murphy
authors.forename: Brian
authors.initials: B
authors.lastname: Khong
authors.forename: Trang H
authors.initials: TH
authors.lastname: La
authors.forename: Christina
authors.initials: C
authors.lastname: Kong
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Fischbein
authors.forename: A Dimitrios
authors.initials: AD
authors.lastname: Colevas
authors.forename: Andrei H
authors.initials: AH
authors.lastname: Iagaru
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
authors.forename: Billy W
authors.initials: BW
authors.lastname: Loo
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D017567:Karnofsky Performance Status; D008198:Lymph Nodes / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009959:Oropharyngeal Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000401:mortality / Q000556:secondary / Q000628:therapy / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18