title: Integrating pretreatment diffusion weighted MRI into a multivariable prognostic model for head and neck squamous cell carcinoma.
abstract: BACKGROUND
  In head and neck squamous cell carcinoma (HNSCC) the ability to anticipate an individual patient's outcome is very valuable. With this study we wanted to assess the prognostic value of pretreatment apparent diffusion coefficient (ADC) in a large patient population and integrate it into a multivariable prognostic model.
  
  
  METHODS
  From 2004 to 2010 175 patients with pathology proven HNSCC were included in this study. All patients underwent a pretreatment MRI with diffusion weighted imaging (DWI) using six b-values. For each tumor, three ADC values were calculated using different b-value combinations: ADC(low) (b 0-50-100 s/mm(2)), ADChigh (b 500-750-1000 s/mm(2)) and ADC(avg) (all b-values). The clinical and radiological variables included: tumor and nodal volume, tumor location and age. Disease recurrence was analyzed using competing risk regression. A prognostic model for disease recurrence was developed, and internal validation was performed using bootstrapping and by dividing patients in three equal sized groups based on prognosis.
  
  
  RESULTS
  One hundred and sixty-one patients were eligible for analysis. Median follow-up was 50 months (range 4-86). A total of 67 patients experienced disease recurrence during follow-up (42%). ADC(high) was a prognostic factor for disease recurrence (adjusted hazard ratio: 1.14 per 10(-4) mm(2)/s, 95% CI 1.04-1.25). Harrell's c-index of the multivariable prognostic model was 0.62 (95% CI 0.56-0.70) after internal validation. The validated 3-year disease recurrence rates for the groups with worst, intermediate, and best prognosis were 56%, 33% and 31% respectively.
  
  
  CONCLUSIONS
  Pretreatment ADC value derived from high b-values is an independent prognostic factor in HNSCC and increases the performance of a multivariable prognostic model in addition to known clinical and radiological variables. Integration of other biomarkers and external validation is necessary to ensure its clinical applicability.
authors.affiliation: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Belgium. Electronic address: maarten.lambrecht@uzleuven.be.
authors.forename: Maarten
authors.initials: M
authors.lastname: Lambrecht
authors.affiliation: Department of Development and Regeneration, KU Leuven, Belgium; Biostatistics Unit, Leuvens Kankerinstituut, University Hospitals Leuven, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Calster
authors.affiliation: Department of Radiology, University Hospitals Leuven, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vandecaveye
authors.affiliation: Department of Radiology, University Hospitals Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: De Keyzer
authors.affiliation: Department of Radiology, University Hospitals Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Roebben
authors.affiliation: Department of Radiology, University Hospitals Leuven, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Hermans
authors.affiliation: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuyts
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Diffusion weighted imaging; Head and neck cancer; Prognostic model