Prognostic value of early changes in neutrophil and lymphocyte measures during chemoradiotherapy for glioblastoma

OBJECTIVES: Elevated baseline neutrophil-lymphocyte ratio (NLR) has been associated with worse outcome in various cancers, including glioblastoma (GBM). This retrospective study assesses if change in NLR during focal radiotherapy (RT) with Temozolomide (TMZ) for newly diagnosed GBM predicts outcome. METHODS: Patients treated with concurrent RT and TMZ for newly diagnosed GBM, between January 2004 and September 2010 were included. Age, ECOG performance status (ECOG-PS), dexamethasone dose, extent of surgery, tumor volume, neutrophil and lymphocyte counts (from baseline to 10 weeks) were collected. Statistical analysis included Kaplan Meier analysis and cox proportional hazard models with univariate (UVA) and multivariable (MVA) analyses. RESULTS: A total of 394 patients with median age of 54 (range 18-73) and median follow up 15.2 months (range 1.6-134.6) were analyzed. Median survival was 15.3 months (95% CI 14.3-16.9 months). Median baseline dexamethasone dose was 8mg (0-30mg) and median time-weighted mean dexamethasone dose (TWMdex) was 4.94mg (0.0 -27.4mg). On UVA, older age (HR 1.034, p2 (HR 1.076, p <0.001) were associated with shorter overall survival (OS). Baseline NLR below the median of 7.5 (HR 0.628, p <0.0001) and decline in NLR (decNLR) (HR 0.644, p <0.0001) were associated with better OS. On MVA, decNLR (HR 0.763, p = 0.02; CI 0.603 - 0.964), age (HR 1.032, p <0.0001; CI 1.018-1.045), TWMdex (HR 1.039, p = 0.002; CI 1.014-1.065) and ECOG-PS (HR 0.593, p = 0.008; CI 0.403-0.873) remained prognostic for OS but not baseline NLR (HR 0.814, p = 0.09; CI 0.641 - 1.032). A low baseline NLR and further decrease in NLR predicted the longest survival (p <0.0001). No significant linear correlation existed between tumor volume and baseline neutrophils (Rho =0.046, p = 0.42), lymphocytes (Rho = -0.015, p = 0.80) or NLR (Rho = 0.05, p = 0.40). CONCLUSIONS: Reduction in NLR during RT and TMZ for newly diagnosed GBM predicted for longer survival, even after accounting for steroid use.