title: Externally validated HPV-based prognostic nomogram for oropharyngeal carcinoma patients yields more accurate predictions than TNM staging.
abstract: OBJECTIVE
  Due to the established role of the human papillomavirus (HPV), the optimal treatment for oropharyngeal carcinoma is currently under debate. We evaluated the most important determinants of treatment outcome to develop a multifactorial predictive model that could provide individualized predictions of treatment outcome in oropharyngeal carcinoma patients.
  
  
  METHODS
  We analyzed the association between clinico-pathological factors and overall and progression-free survival in 168 OPSCC patients treated with curative radiotherapy or concurrent chemo-radiation. A multivariate model was validated in an external dataset of 189 patients and compared to the TNM staging system. This nomogram will be made publicly available at www.predictcancer.org.
  
  
  RESULTS
  Predictors of unfavorable outcomes were negative HPV-status, moderate to severe comorbidity, T3-T4 classification, N2b-N3 stage, male gender, lower hemoglobin levels and smoking history of more than 30 pack years. Prediction of overall survival using the multi-parameter model yielded a C-index of 0.82 (95% CI, 0.76-0.88). Validation in an independent dataset yielded a C-index of 0.73 (95% CI, 0.66-0.79. For progression-free survival, the model's C-index was 0.80 (95% CI, 0.76-0.88), with a validation C-index of 0.67, (95% CI, 0.59-0.74). Stratification of model estimated probabilities showed statistically different prognosis groups in both datasets (p<0.001).
  
  
  CONCLUSIONS
  This nomogram was superior to TNM classification or HPV status alone in an independent validation dataset for prediction of overall and progression-free survival in OPSCC patients, assigning patients to distinct prognosis groups. These individualized predictions could be used to stratify patients for treatment de-escalation trials.
authors.affiliation: Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, The Netherlands; Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Emmanuel_Rios@dfci.harvard.edu.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rios Velazquez
authors.affiliation: Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Hoebers
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Hugo J W L
authors.initials: HJ
authors.lastname: Aerts
authors.affiliation: Department of Pathology, Maastricht University Medical Centre+, GROW Research Institute, The Netherlands.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rietbergen
authors.affiliation: Department of Pathology, Maastricht University Medical Centre+, GROW Research Institute, The Netherlands.
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
authors.affiliation: Department of Pathology, Maastricht University Medical Centre+, GROW Research Institute, The Netherlands.
authors.forename: René C
authors.initials: RC
authors.lastname: Leemans
authors.affiliation: Department of Pathology, Maastricht University Medical Centre+, The Netherlands.
authors.forename: Ernst-Jan
authors.initials: EJ
authors.lastname: Speel
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Maastricht University Medical Centre+, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Straetmans
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Maastricht University Medical Centre+, The Netherlands.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kremer
authors.affiliation: Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, The Netherlands.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D059248:Chemoradiotherapy / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049451:Nomograms; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D012737:Sex Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
keywords: Decision support systems; Human papillomavirus; Oropharyngeal cancer; Outcome prediction; Predictive nomogram