title: Comparative effectiveness of induction chemotherapy for oropharyngeal squamous cell carcinoma: A population-based analysis.
abstract: OBJECTIVE
  Despite several randomized trials, the optimal chemotherapy paradigm for locally advanced oropharyngeal carcinoma (OPSCC) is controversial. This population-based analysis assessed the overall survival (OS) benefit of induction chemotherapy (IC) for patients with stage III-IVB OPSCC.
  
  
  METHODS
  Patients in the National Cancer Database with stage III-IVA-B OPSCC treated with curative-dose radiotherapy and IC or concurrent chemotherapy (CRT) between 2003 and 2011 were eligible. The primary outcome was OS, and secondary endpoints included OS for high-risk (T4 and/or N3 disease) and human papillomavirus (HPV) subsets.
  
  
  RESULTS
  Of the 14,856 analyzed patients, 78% and 22% received CRT and IC, respectively. With a median follow-up for surviving patients of 44 months, the 5-year OS probability for the entire cohort was 66% (66% CRT vs. 64% IC, p=0.022). Multivariable survival analysis showed no significant difference between CRT and IC (hazard ratio, HR, 0.95 for IC, p=0.255), and sensitivity analyses to adjust for immortal time bias brought the HR to 1.0 (p=0.859). There was also no OS difference for high-risk patients. There was a trend in favor of CRT for HPV-positive OPSCC (HR 1.63 with IC, p=0.064), with a significant OS benefit for HPV-negative, high-risk OPSCC (HR 0.63, p=0.048).
  
  
  CONCLUSIONS
  For the vast majority of patients, including HPV-positive individuals, there was no difference in OS with IC, arguing for CRT to remain as the standard therapy. Subset analysis revealed a small cohort of aggressive cancer (T4/N3 HPV-negative) which may benefit from from IC, although selection bias could not be ruled out.
authors.affiliation: Department of Radiation Oncology and Division of Outcomes and Health Services Research, UT Southwestern Medical Center, Dallas, TX, United States. Electronic address: david.sher@utsouthwestern.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sher
authors.affiliation: Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Schwartz
authors.affiliation: Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Lucien
authors.initials: L
authors.lastname: Nedzi
authors.affiliation: Department of Medical Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Saad
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Medical Oncology, UT Southwestern Medical Center, Dallas, TX, United States.
authors.forename: Randall
authors.initials: R
authors.lastname: Hughes
authors.affiliation: Department of Medical Oncology, Rush University Medical Center, Chicago, IL, United States.
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Fidler
authors.affiliation: Department of Radiation Oncology, University of Chicago, Chicago, IL, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Koshy
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
keywords: Chemoradiotherapy; Combined modality therapy; Head and neck cancer; Human papillomavirus; Induction chemotherapy; Oropharyngeal cancer; Outcomes research