Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio with Poor Clinical Outcomes in Patients with Human Papillomavirus-Negative Oropharyngeal Cancers

Alexander J. Lin, Margery Gang, Yuan James Rao, Jian Campian, Mackenzie Daly, Hiram Gay, Peter Oppelt, Ryan S. Jackson, Jason Rich,Randal Paniello, Jose Zevallos, Dennis Hallahan, Douglas Adkins, Wade Thorstad. JAMA Otolaryngology – Head and Neck Surgery 2019 Read More


Importance: Better biomarkers are needed for human papillomavirus (HPV)-negative oropharyngeal cancer (OPC) to identify patients at risk of recurrence. Lymphopenia and an elevated ratio of neutrophils to lymphocytes (NLR) have been associated with poor disease outcomes in a number of solid tumors. Objective: To test the hypothesis that postradiotherapy lymphopenia and elevated NLR are associated with poor clinical outcomes. Design, Setting, and Participants: This single-institution retrospective analysis included patients with HPV-negative OPC treated from January 1, 1997, through January 4, 2017. Median follow-up was 37 months (range, 2-197 months). A total of 108 patients with HPV-negative OPC and at least 1 complete blood cell count 2 to 12 months after the start of radiotherapy were included. Data were analyzed from August 26 to September 7, 2017. Interventions: Surgery followed by radiotherapy vs definitive radiotherapy, with or without chemotherapy. Main Outcomes and Measures: Absolute lymphocyte (ALC) and absolute neutrophil (ANC) counts were tested as variables affecting locoregional control, recurrence-free survival, and overall survival. Results: Of a total of 108 patients included in the analysis (87.0% male; mean age, 56 years [range, 35-84 years]), 57 received surgery followed by postoperative radiotherapy and 51 received definitive radiotherapy. During treatment, 67 of 79 patients (84.8%) had grades 3 to 4 lymphopenia and 17 of 79 (21.5%) had grade 4 lymphopenia. The ANC recovered by 6 months after radiotherapy, but ALC remained depressed to 1 year after radiotherapy. Posttreatment lymphopenia and elevated NLR were associated with worse recurrence-free and overall survival. The estimated 3-year LRC in patients with and without grades 3 to 4 lymphopenia at 3 months after radiotherapy start was 73% vs 82% (hazard ratio [HR], 0.58; 95% CI, 0.19-1.8); estimated 3-year recurrence-free survival, 36% vs 63% (HR, 0.45; 95% CI, 0.23-0.87); and estimated 3-year overall survival, 34% vs 64% (HR, 0.45; 95% CI, 0.23-0.88). In multivariable analysis, an association with worse overall survival was found for definitive radiotherapy (HR, 3.3; 95% CI, 1.6-7.1) and grades 3 to 4 lymphopenia (HR, 2.6; 95% CI, 1.3-5.5) at 3 months after radiotherapy. Conclusions and Relevance: Lymphopenia and NLR as early as 3 months after treatment start may serve as biomarkers of clinical outcomes in patients with HPV-negative OPC. These patients may benefit from adjuvant treatment intensification or closer surveillance. © 2019 American Medical Association. All Rights Reserved.

Full Text


Posted on April 10, 2019
Posted in: HPAN, Neurodegeneration Authors: