Peripheral blood neutrophil-to-lymphocyte ratio in NK/T-cell lymphoma - prognostic significance and correlation with tumor transcriptomic profiles

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Lymphomas
Pathology/Molecular Biology
Presenter Tan Khee Ming
Citation Annals of Oncology (2018) 29 (suppl_9): ix87-ix93. 10.1093/annonc/mdy437
Authors T. Khee Ming1, B. Chia2, J.Q. Lim2, L.P. Khoo3, C.L. Cheng4, L. Tan4, J.Y. Chan3, E.Y.L. Poon3, N. Somasundaram3, M. Farid5, T.P.L. Tang3, M. Tao3, D.M.Z. Cheah2, Y. Laurensia2, J.W.L. Pang2, S.J. Kim6, W.S. Kim6, C.K. Ong2, S.T. Lim3, T. Song2
  • 1Ntu Lkcsom, Nanyang Technological University, 639798 - Singapore/SG
  • 2Division Of Medical Oncology, Lymphoma Genomic Translational Research Laboratory, Singapore/SG
  • 3Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 4Department Of Anatomical Pathology, Singapore General Hospital, Singapore/SG
  • 5Division Of Medical Oncology, National Cancer Centre Singapore, Singapore/SG
  • 6Sungkyunkwan University School Of Medicine, Samsung Medical Centre, Korea/KR

Abstract

Background

Extranodal NK/T-cell lymphoma, nasal type (NKTCL) is an aggressive Epstein-Barr Virus-associated lymphoproliferative malignancy typified by local immune cell infiltration and variable states of systemic inflammation. This study aims to investigate the clinical relevance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTCL.

Methods

Retrospective review of patients with histologically-proven NKTCL and available blood counts at diagnosis (1993-2016) from the National Cancer Centre Singapore and Samsung Medical Center, South Korea was completed. An optimal cutoff for high NLR (>3.5) in predicting overall survival (OS) was determined using receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariate Cox proportional models. Gene expression profiling was performed for each subgroup (n = 4 per group). NLR-associated signaling pathways were explored with gene set enrichment analysis (GSEA) using the MSigDB Hallmark gene set.

Results

The median age at diagnosis was 54 years (range, 17-86), with a male preponderance (70.8%). Median NLR was 2.6 (range, 0.7-24.5) and 59 patients (33.1%) possessed high NLR. High NLR was associated with advanced age ≥60 (p = 0.032), ECOG score ≥2 (p = 0.0025), elevation of lactate dehydrogenase (p = 0.02) and IPI score 3-4 (p = 0.014). Estimated 5-year OS was 53% in patients with low NLR and 25% in those with high NLR. In multivariate analysis, high NLR, in addition to B-symptoms and advanced stage, were independently associated with both worse overall survival (HR 2.08; 95% CI 1.36 to 3.18; p = 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p = 0.0128). In subgroup analysis, the prognostic ability of NLR on OS was observed in both Singapore an (p = 0.0072) and Korean (p = 0.031) cohorts. GSEA suggests that high NLR is associated with tumors harboring upregulated DNA repair genes including POLD3 and ERCC2 (false discovery rate, 0.137; p < 0.001).

Conclusions

High NLR is correlated with distinct tumor transcriptomic profiles in NKTCL and is an independent marker of poor survival outcomes.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

SGH IRB.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.