The impact of neutrophils-to-lymphocytes ratio on survival in patients affected by brain metastases and treated with Gamma Knife Radiosurgery

Background The Neutrophil-to-Lymphocyte ratio (NLR) is a biomarker for host systemic inflammation. Elevated NLR may result from neutrophilia, lymphopenia or both and is associated with poor prognosis and treatment responses in various malignant tumors, such as breast, gastric, colorectal and lung cancer. It was found that in patients treated with GK-SRS for brain metastases (BM) from non-small cell lung cancer (NSCLC), median survival was significantly longer in patients with NLR < 5 at the time of radiosurgery and after treatment (within 1 month from SRS). High percentage of neutrophils, low percentage of lymphocytes and elevated platelet-to-lymphocyte ratio were predictive of poor OS in patients with brain metastases. Further evidences are needed to support and better define these findings. Material and Methods We retrospectively examined 111 consecutive patients with BMs from NSCLC (95 patients) and melanoma (16 patients) treated with GK-SRS. A total of 695 lesions were treated (median lesion number per patient 6; range 1-18), the median volume was 0.108 cc (range 0.004-33.44 cc). NLR was calculated using N/L, where N and L, respectively, refer to peripheral blood neutrophils (N) and lymphocyte (L) counts at the timepoint nearest to the SRS treatment. Kaplan-Meier analysis described the survival time according to NLR. Univariable and multivariable Cox regression analyses were used to confirm the impact of NLR on overall survival. Results Median (IQR) age at diagnosis of brain metastases was 64 yrs (55-70), median (IQR) NLR was 6.7 (1.3-32), and median (IQR) overall survival was 13.5 months (1-42). At univariable Cox-regression analyses, lower NLR was associated with improved overall survival (HR: 1.05; p=0.004). Total number of lymphocytes, neutrophils and monocytes were not associated with improved overall survival (all p>0.1). At multivariable Cox regression analyses, after adjusting for patient age, sex and the use of DEX therapy, NLR represented an independent predictor of overall survival (HR: 1.06; p=0.003). Conclusion NLR represents an independent prognostic factor in patients affected by BMs from NSCLC and melanoma. Inflammation and immunity may play a critical role in these patients. Further analysis examining more specific neutrophils or lymphocytes subsets may increase our understanding of cancer etiology and progression.