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

Sze Wah Samuel Chan; Elliot Smith; Reenika Aggarwal; Karmugi Balaratnam; RuiQi Chen; Katrina Hueniken; Rouhi Fazelzad; Jessica Weiss; Shirley Jiang; Frances A Shepherd; Penelope A Bradbury; Adrian G Sacher; Natasha B Leighl; Wei Xu; M Catherine Brown; Lawson Eng; Geoffrey Liu

doi:10.1016/j.cllc.2021.01.002

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

Clin Lung Cancer. 2021 Sep;22(5):390-407. doi: 10.1016/j.cllc.2021.01.002. Epub 2021 Jan 10.

Authors

Sze Wah Samuel Chan¹, Elliot Smith¹, Reenika Aggarwal², Karmugi Balaratnam¹, RuiQi Chen¹, Katrina Hueniken¹, Rouhi Fazelzad³, Jessica Weiss⁴, Shirley Jiang¹, Frances A Shepherd¹, Penelope A Bradbury¹, Adrian G Sacher¹, Natasha B Leighl¹, Wei Xu⁴, M Catherine Brown¹, Lawson Eng¹, Geoffrey Liu⁵

Affiliations

¹ Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
² Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³ Library Sciences, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
⁴ Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
⁵ Medical Oncology and Hematology, Princess Margaret Cancer Centre, and Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada; Departments of Medical Biophysics, Pharmacology, and Toxicology, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: geoffrey.liu@uhn.ca.

PMID: 33582072
DOI: 10.1016/j.cllc.2021.01.002

Abstract

Background: Systemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non-small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, 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 (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed.

Results: From 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, 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 NLR (aHR = 1.46), while for PFS, only late stage derived NLR (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.

Conclusion: This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated 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.

Keywords: EGFR; LDH; NLR; NSCLC; Prognostic markers.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Biomarkers*
Carcinoma, Non-Small-Cell Lung*
Epidermal Growth Factor / genetics*
Humans
Mutation / genetics*
Survival Analysis*

Substances

Biomarkers
Epidermal Growth Factor