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

Abstract

Importance\nBetter 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.\n\n\nObjective\nTo test the hypothesis that postradiotherapy lymphopenia and elevated NLR are associated with poor clinical outcomes.\n\n\nDesign, Setting, and Participants\nThis 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.\n\n\nInterventions\nSurgery followed by radiotherapy vs definitive radiotherapy, with or without chemotherapy.\n\n\nMain Outcomes and Measures\nAbsolute lymphocyte (ALC) and absolute neutrophil (ANC) counts were tested as variables affecting locoregional control, recurrence-free survival, and overall survival.\n\n\nResults\nOf 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],\u20090.58; 95% CI, 0.19-1.8); estimated 3-year recurrence-free survival, 36% vs 63% (HR,\u20090.45; 95% CI, 0.23-0.87); and estimated 3-year overall survival, 34% vs 64% (HR,\u20090.45; 95% CI, 0.23-0.88). In multivariable analysis, an association with worse overall survival was found for definitive radiotherapy (HR,\u20093.3; 95% CI, 1.6-7.1) and grades 3 to 4 lymphopenia (HR,\u20092.6; 95% CI, 1.3-5.5) at 3 months after radiotherapy.\n\n\nConclusions and Relevance\nLymphopenia 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.