title: Exploring the Impact of Human Papillomavirus Status, Comorbidity, Polypharmacy, and Treatment Intensity on Outcome of Elderly Oropharyngeal Cancer Patients Treated With Radiation Therapy With or Without Chemotherapy.
abstract: To explore the impact of tumor human papillomavirus (HPV) status, comorbidity, polypharmacy, and treatment intensity on overall survival (OS) of elderly oropharyngeal cancer (OPC) patients.
  
  
  
  All elderly (>70 years) OPC patients receiving definitive (chemo-) radiation therapy in 2000 to 2013 were reviewed. Charlson comorbidity index (CCI, comorbidity alone) and the comorbidity-polypharmacy score (CPS, comorbidity and medication) were calculated. Overall survival was compared between HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Multivariable analyses (MVA) incorporating either the CCI (MVA-CCI) or the CPS (MVA-CPS) identified survival predictors.
  
  
  
  Among 231 of 287 patients (80%) with p16 staining, 117 were HPV+ and 114 HPV-. Systemic treatments were administered in 48 patients (21%) (chemotherapy 17; epidermal growth factor receptor inhibitor 31). The distribution of CCI (P=.59), CPS (P=.23), and age (P=.50) were similar between HPV+ versus HPV- cohorts. Median follow-up was 4.3 years. The HPV+ patients had better 5-year OS (57% vs 32%, P<.001) versus HPV- patients. Multivariable analysis adjusted for T-/N-category confirmed that HPV+ status (MVA-CCI: hazard ratio [HR] 0.58, P=.01; MVA-CPS: HR 0.60, P=.02), Zubrod scale score (0-1) (MVA-CCI: HR 0.44, P<.001; MVA-CPS: HR 0.43, P<.001), and higher radiation therapy dose (MVA-CCI: HR 0.97, P=.001; MVA-CPS: HR 0.96, P<.001) were correlated with higher OS. A marginal inverse correlation between CPS and OS was observed in the entire cohort (HR 1.05, P=.05) and was stronger for the HPV+ cohort (HR 1.11, P=.02). Nonsignificant higher OS was also found with ≤20 pack-years of smoking (MVA-CCI: P=.10; MVA-CPS: P=.15) and with systemic treatments (MVA-CCI: P=.13; MVA-CPS: P=.19). No association with OS was found for CCI (P=.46).
  
  
  
  Elderly HPV+ OPC patients have longer survival than their HPV- counterparts. Lower Zubrod scale score and higher radiation therapy dose are associated with longer OS, whereas fewer smoking pack-years and systemic agents have nonsignificant associations. Comorbidity-polypharmacy score, but not CCI, is correlated with OS, especially in HPV+ patients, suggesting the potential importance of assessing polypharmacy in addition to comorbidity burden in this population.
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caparrotti
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology-Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Bratman
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.affiliation: Department of Biostatistics, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Meredith
authors.initials: M
authors.lastname: Giuliani
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Department of Otolaryngology-Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Waldron
authors.affiliation: Division of Medical Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Hansen
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Department of Pathology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.affiliation: Department of Pathology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ilan
authors.initials: I
authors.lastname: Weinreb
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Biostatistics, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yuyao
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Biostatistics, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, The Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: shaohui.huang@rmp.uhn.on.ca.
authors.forename: Shao Hui
authors.initials: SH
authors.lastname: Huang
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015897:Comorbidity; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000821:virology*; D017063:Outcome Assessment, Health Care; D027383:Papillomaviridae / Q000302:isolation & purification; D019338:Polypharmacy; D011832:Radiation Injuries / Q000473:pathology; D011879:Radiotherapy Dosage; D012907:Smoking / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors