Abstract 1575: DNA methylation-derived neutrophil-to-lymphocyte ratio and survival among pediatric medulloblastoma patients

Abstract

Background/Objectives: Medulloblastoma is the most common malignant brain tumor diagnosed in children. Current risk-stratification methods of pediatric medulloblastoma do not fully explain the observed variability in clinical outcomes. Methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) captures immune-specific information and has been identified as a potential prognostic biomarker of outcomes in various cancers, including adult brain tumors. Therefore, we evaluated the association between blood-derived mdNLR and overall survival in a cohort of patients with pediatric medulloblastoma. Design/Methods: We identified pediatric patients diagnosed and treated for medulloblastoma at Texas Children’s Cancer Center between 1995 and 2015. Peripheral blood DNA methylation was measured using the Infinium Human Methylation 450K Beadchip. Methylation data underwent quality control, including beta-mixture quantile normalization and batch correction. Immune cell proportions (CD4+ T-Cells, CD8+ T-Cells, B-cells, natural killer cells, monocytes, and granulocytes) were estimated using cellular deconvolution methods and used to estimate mdNLR, which was then log-transformed to improve normality. Cox regression models were estimated to evaluate the association between mdNLR and overall survival. Results: Of the 78 eligible patients include in this analysis, 83% (n=65) were alive at last follow-up (median follow-up=7.8 years). Deceased patients (n=13; median follow-up=2.6 years) had a higher mean mdNLR than patients who were alive at last contact (12.3 vs. 4.0, P = 0.046). Elevated log-transformed mdNLR was associated with an increased risk of death in both unadjusted models (HR=1.68, 95%CI: 1.11-2.55) and models accounting for age, sex, race, and clinical risk group (HR=1.97, 95%CI: 1.12-3.45). Conclusion: We identified a significant association between peripheral blood mdNLR and survival in pediatric medulloblastoma. As a promising prognostic biomarker of outcomes, mdNLR captures immune-specific information and is a potential avenue of research in settings where cytologic determination of NLR may not be possible. Future work should investigate the relationship between elevated mdNLR and specific pediatric medulloblastoma molecular subtypes. Citation Format: Vidal M. Arroyo, Philip J. Lupo, Michael E. Scheurer, Surya P. Rednam, Jeffrey C. Murray, M F. Okcu, Murali M. Chintagumpala, Austin L. Brown. DNA methylation-derived neutrophil-to-lymphocyte ratio and survival among pediatric medulloblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1575.