Survival Analysis of Patients With Advanced-Stage Oropharyngeal Cancer Stratified by Molecular Profile and Treatment: Survivorship

Abstract

Purpose/Objective(s): To determine differences in survival outcomes in patients with advanced stage oropharyngeal squamous cell carcinoma (OPSCC) when stratified by treatment and molecular profile. Materials/Methods: Demographic, pathologic and survival data was obtained from all patients diagnosed and treated for OPSCC from 1998-2010 at a tertiary care center (University of Alberta). Tissue microarrays (TMAs) were constructed to include all patients treated within this time frame with sufficient pathologic specimen available (nZ334). TMAs were stained by immunohistochemistry for p16, EGFR, Ki-67, Bcl-XL and p53, and digitally quantified in comparison to positive and negative controls. Patients were stratified by molecular profile using standardized expression cutoffs. Molecular profiles were then used to stratify patients who received the following treatment modalities: 1) primary surgery + chemoradiation (S+CRT), 2) primary surgery + post-operative radiation (S+RT) and 3) primary chemoradiation +/salvage surgery (CRT). Disease-specific (DSS) and overall survival was calculated for each stratum using Kaplan-Meir analysis. Hazard ratios and multivariate analysis was performed using Cox regression. Results: Distinct twoand five-year survival curves were obtained for each treatment stratum. When considering p16 status, 5-year DSS was highest for patients who received S+CRT (84.8% for p16+ and 60.8% for p16-), followed by S+RT (77.5% for p16+ and 54% for p16-) and CRT (55.2% for p16+ and 38.1% for p16-). Remarkably, the 5-year DSS of patients treated with S+CRT with low tumor EGFR levels was 100%. Patients with p53 positivity had improved DSS with surgical modalities. Bcl-XL levels alone were not associated with a significant difference in survival outcome. Elevated Ki-67 levels were associated with improved outcomes in patients receiving radiation therapy but low Ki-67 levels stratified patients into the poorest outcome group with a 5-year DSS of 18%. Conclusions: To our knowledge, this represents the largest cohort of advanced stage OPSCC survival comparing surgical and non-surgical treatment modalities, stratified by clinically significant biomarkers. Triple modality therapy provides optimal survival outcomes for patients with advanced stage OPSCC regardless of molecular profile. Author Disclosure: V.L. Biron: None. D.A. O’Connell: None. A.C. Klimowicz: None. L. Puttagunta: None. J. Harris: None. H. Seikaly: None.