title: Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Half of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort.
  
  
  METHODS
  Eligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients.
  
  
  RESULTS
  The validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (kappa=0.64), and very good rater agreement when compared with the standard (kappa=0.87).
  
  
  CONCLUSIONS
  We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.
authors.affiliation: Einstein/Montefiore Head and Neck Research Group, Department of Pathology, Bronx, NY, USA. MGensler@UAB.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: Brandwein-Gensler
authors.forename: Richard V
authors.initials: RV
authors.lastname: Smith
authors.forename: Beverly
authors.initials: B
authors.lastname: Wang
authors.forename: Carla
authors.initials: C
authors.lastname: Penner
authors.forename: Andrea
authors.initials: A
authors.lastname: Theilken
authors.forename: Darcy
authors.initials: D
authors.lastname: Broughel
authors.forename: Bradley
authors.initials: B
authors.lastname: Schiff
authors.forename: Randall P
authors.initials: RP
authors.lastname: Owen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Smith
authors.forename: Cathy
authors.initials: C
authors.lastname: Sarta
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hebert
authors.forename: Rick
authors.initials: R
authors.lastname: Nason
authors.forename: Marie
authors.initials: M
authors.lastname: Ramer
authors.forename: Mark
authors.initials: M
authors.lastname: DeLacure
authors.forename: David
authors.initials: D
authors.lastname: Hirsch
authors.forename: David
authors.initials: D
authors.lastname: Myssiorek
authors.forename: Keith
authors.initials: K
authors.lastname: Heller
authors.forename: Michael
authors.initials: M
authors.lastname: Prystowsky
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Abdissa
authors.initials: A
authors.lastname: Negassa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000401:mortality / Q000473:pathology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000145:classification / Q000401:mortality / Q000473:pathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008350:Manitoba / Q000453:epidemiology; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D015996:Survival Rate