Abstract
The purpose of the present study was to evaluate the prognostic significance of the pre- treatment C-reactive protein (CRP) level in a cohort of 503 patients with oral and oropharyngeal cancer treated at a tertiary academic center between 2000 and 2017. Cancer-specific survival (CSS), overall survival (OS) and loco-regional control (LC) were calculated using Kaplan-Meier analysis. To evaluate the prognostic value of the CRP level for the clinical endpoints, univariate and multivariate Cox regression models were applied. The median follow-up period was 61 months. Patients were divided into elevated CRP (≥5 mg/L) and normal CRP groups, according to pre-treatment plasma levels. An increased CRP level was significantly associated with shorter CSS (p < 0.001, log-rank test), as well as with shorter OS (p < 0.001, log-rank test) and loco-regional control (p = 0.001, log-rank test). In addition, multivariate analysis identified CRP as an independent predictor for CSS (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.08–2.35; p = 0.020) as well as for OS (HR 1.62, 95%CI 1.17–2.24; p = 0.004) and LC (HR 1.50, 95%CI 1.06–2.14; p = 0.023). In subgroup analysis, Kaplan Meier curves revealed that an elevated pre-treatment CRP level was a consistent prognostic factor for poor CSS (p = 0.003, log-rank test), OS (p = 0.001, log-rank test), and LC (p = 0.028, log-rank test) in patients treated with definitive (chemo-) radiotherapy, whereas a significant association in patients undergoing surgery and postoperative radiotherapy was not detected. The pre-treatment CRP level seems to represent a prognostic factor for CSS, OS, and LC in patients with oral and oropharyngeal cancer, particularly in those treated with definitive (chemo-) radiotherapy. Additional large-scale prospective studies are warranted to confirm and extend our findings.
Highlights
Oral and oropharyngeal squamous cell carcinoma (OOSCC) represents a major cause of morbidity and mortality worldwide
The C-reactive protein (CRP) level significantly correlated with age, alcohol abuse, pre-treatment neutrophil/lymphocyte ratio (NLR)
Univariate Cox regression analysis demonstrated that a CRP level ≥5.0 mg/L was a significant prognostic factor for decreased Cancer-specific survival (CSS) (HR 1.95, 95%confidence intervals (CIs) 1.37–2.78; p < 0.001), overall survival (OS) (HR 1.85, 95%CI 1.38–2.47; p < 0.001) and loco-regional control (LC) (HR 1.73, 95%CI 1.25–2.40; p = 0.001)
Summary
Oral and oropharyngeal squamous cell carcinoma (OOSCC) represents a major cause of morbidity and mortality worldwide. At the time of diagnosis, approximately two-thirds of patients present with advanced-stage disease with either loco-regional spread to the lymph nodes or distant metastasis [1]. Within two years after treatment, up to 50% of patients experience loco-regional recurrence with limited options for salvage surgery or re-irradiation treatment [2]. The prognosis of OOSCC depends on biological cancer characteristics as well as on patient and treatment characteristics. A large number of translational research studies have revealed an association of various molecular biomarkers with clinical outcome in OOSCC. Molecular predictors of prognosis (e.g., DNA methylation markers or miRNA expression) may provide additional prognostic and/or predictive information, but high costs, lack of standardization and regional availability limit their application in routine clinical practice [3,4]
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