Systemic Inflammatory Markers of Survival in Epidermal Growth Factor-mutated Non-Small Cell Lung Cancer: Single Institution Analysis, Systematic Review and Meta-Analysis

Abstract Background Systemic inflammatory response (SIR) may influence prognosis in epidermal-growth-factor-receptor-mutated (EGFRm) non-small-cell-lung-cancer (NSCLC). Pre-treatment SIR markers (neutrophil-to-leukocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) and Lung Immune Prognostic Index (LIPI)) were assessed as prognostic factors in NSCLC survival. Patients and Methods Retrospective survival analysis (OS, overall survival; PFS, progression-free survival) of EGFRm NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage, for individual SIR variables, dichotomized by optimal cut-off points, using Kaplan-Meier survival analysis and multivariable Cox-proportional-hazard modelling. A systematic review and meta-analysis of known SIR studies in late-stage EGFR patients were also performed. Results From 2012-2019 in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high vs low NLR were 2.12 for early-stage and 1.79 for late-stage. Additionally, late-stage cohorts had significant associations: high vs low dNLR, aHR=1.53; LMR, aHR=0.62; LDH, aHR=2.04; and LIPI, aHR=2.04. Similar patterns were found for PFS in early-stage NLR (aHR=1.96) and late-stage (aHR=1.46), while for PFS, only late-stage dNLR (aHR=1.34), LDH (aHR=1.75) and LIPI (aHR=1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH and LIPI were all significantly associated with OS and PFS in the late-stage. Conclusions This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late-stage EGFR NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions.