Prognostic Significance of Pretreatment Total Lymphocyte Count, Neutrophil-to-Lymphocyte Ratio, and Platelet-to-Lymphocyte Ratio in Limited-Stage Small Cell Lung Cancer

Abstract

Inflammation and immunity are important in cancer development and progression. We sought reliable inflammatory and immunologic markers of prognosis in patients with limited-stage small cell lung cancer (LS-SCLC). We retrospectively identified and analyzed patients with LS-SCLC who received chemoradiotherapy or radiotherapy at a single institution from 2002 through 2015. Selection criteria were pathologically proven SCLC, clinically LS I‒IIIB disease, receipt of definitive radiation therapy with curative intent, and availability of laboratory data before initiation of curative treatment. Total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were extracted from pretreatment complete blood counts (CBCs) with differential along with other potential predictors of overall survival (OS) and progression-free survival (PFS). Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values for pretreatment TLC, NLR, and PLR that would predict survival. The survival function was carried out using Kaplan-Meier estimates. The Cox’s proportional hazard model was used for multivariate analysis to assess the effect of patient, tumor and other predictor factors of significance on the end points. A total of 122 patients met the eligibility criteria. Mean values and standard deviations of pretreatment TLC, NLR, and PLR were 1.86 ± 0.88 × 103/μL, 3.44 ± 3.69, and 170.53 ± 101.56, respectively. Optimal cutoff values for these factors were 1.9 × 103/μL for TLC, 2.9 for NLR, and 140.1 for PLR. Patients with higher pretreatment TLC (≥1.9 × 103/μL) had superior median OS time and 2-year OS rate compared with patients with lower pretreatment TLC (<1.9 × 103/μL) (17.4 vs 15.7 months; 33% vs 29%, P = 0.029). On the other hand, patients with higher pretreatment NLR (≥2.9) and higher PLR (≥140.1) had worse median OS time and 2-year OS rate than did patients with lower pretreatment NLR (<2.9) and PLR (<140.1) (14.9 vs 17.8 months, 29% vs 31%, P = 0.026; and 14.8 vs 18.9 months, 24% vs 37%, P = 0.009, respectively). The final multivariate Cox regression analysis adjusted for age, performance status, and tumor-nodes-metastasis disease stage showed that higher pretreatment TLC (≥1.9 × 103/μL) was associated with superior OS (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.32–0.94, P = 0.028) and higher pretreatment NLR (≥2.9) (HR = 1.76, 95% CI = 1.08–2.87, P = 0.025) and higher PLR (≥140.1) (HR = 1.74, 95% CI = 1.06–2.84, P = 0.028) were associated with inferior OS. Pretreatment baseline TLC, NLR, and PLR were all found to be associated with survival in patients with LS-SCLC. To our knowledge, this is the first study to show that baseline lymphopenia (defined as TLC) is an important indicator of dismal prognosis in patients with LS-SCLC.