World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Original Article

Volume 8, Number 6, December 2017, pages 180-187


Neutrophil-to-Lymphocyte Ratio Predicts Overall Survival of Advanced Non-Small Cell Lung Cancer Harboring Mutant Epidermal Growth Factor Receptor

Figures

Figure 1.
Figure 1. Kaplan-Meier curves of overall survival. (a) Neutrophil-to-lymphocyte ratio (NLR). (b) Lymphocyte-to-monocyte ratio (LMR).
Figure 2.
Figure 2. Kaplan-Meier curves of progression-free survival (PFS). (a) Neutrophil-to-lymphocyte ratio (NLR). (b) Lymphocyte-to-monocyte ratio (LMR).

Tables

Table 1. Comparisons of Backgrounds and Laboratory Data Between Two Groups Divided According to Neutrophil-to-Lymphocyte and Lymphocyte-to-Monocyte Ratios
 
GroupsALLNLRLMR
< 2.11≥ 2.11P< 5.09≥ 5.09P
aMann-Whitney test. bFisher’s extract test. cDouble mutations. Exon 19del + Exon 21 L858R and Exon 21 L858R + Exon 18 G719S in each one case. Ad: adenocarcinoma; BMI: body mass index; del: deletion; CI: confidence interval; ECOG PS: Eastern Cooperative Oncology Group performance status; LMR: lymphocyte-to-monocyte ratio; Lymph: lymphocyte; met: metastasis; Mono: monocyte; mt: mutation; Neut: neutrophil; NLR: neutrophil-to-lymphocyte ratio; Rec: post-surgical recurrence; SD: standard deviation.
N152549810547
Backgrounds
  Age (years, mean ± SD)70.3 ± 10.370.5 ± 8.670.2 ± 11.10.66a70.4 ± 10.770.1 ± 9.40.69a
  Sex (N, male/female)57/9515/3942/560.08b45/6012/350.047b
  Histology (N, Ad/others)148/454/094/40.30b101/447/00.31b
  Stage (N, IIIA/IIIB/IV/Rec)10/3/102/374/2/30/186/1/72/190.10b6/1/74/244/2/28/130.32b
  Distant met (N)13246860.44b95390.28b
    Brain met (N)3213190.54b21110.67b
    Liver met (N)143110.38b1041.00b
    Bone met (N)551144< 0.01b45100.01b
  ECOG PS (N, 0 - 1/2/3/4)111/32/7/249/5/0/062/27/7/2< 0.01b68/28/7/243/4/0/0< 0.01b
  BMI (mean ± SD)21.8 ± 4.122.0 ± 3.321.6 ± 4.50.13a21.7 ± 4.422.0 ± 3.40.30a
  EGFR mt (N)c
    Ex 19del7427475024
    Ex 21 point mt7425495321
    Minor mt63333
    Ex19 del vs. other74/7827/2747/510.87b50/5524/230.73b
Laboratory data
  Neut (cells/µL)4,183 ± 1,9563,075 ± 1,0954,793 ± 2,060< 0.01a4,606 ± 2,0933,237 ± 1,155< 0.01a
  Lymph (cells/µL)1,496 ± 6051,962 ± 5541,239 ± 463< 0.01a1,338 ± 5071,850 ± 659< 0.01a
  Mono (cells/µL)411 ± 177349 ± 123446 ± 193< 0.01a468 ± 175286 ± 101< 0.01a

 

Table 2. Treatment and Outcomes
 
GroupAllNLRLMR
< 2.11≥ 2.11Pa< 5.09≥ 5.09Pa
aFisher’s extract test. Afa: afatinib; CI: confidence interval; DCR: disease control rate; Erl: erlotinib; Gef: gefitinib; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; RR: response rate; TKI: tyrosine kinase inhibitor; TRT: thoracic radiotherapy.
N152549810547
TKI choice (N, Gef/Erl/Afa)107/36/943/10/164/26/80.1272/27/635/9/30.68
TKI line (N, first/second/≥ third)104/38/1137/14/467/24/71.0071/27/733/11/30.96
Pre TKI treatment (N)4918310.8634100.18
  Platinum-based3914251.003070.10
  Curative-intent TRT8351.00621.00
Post TKI treatment (N)9841570.0364340.20
  Cytotoxic drugs6226360.2340220.37
    Platinum-based2710171.0018130.19
  Osimertinib14591.00950.76
  Re-challenge of TKI6227350.1242220.48
Palliative radiotherapy (N)5718390.4938190.72
TKI Response (N)
  Complete response53223
  Partial response8836525533
  Stable disease291118218
  Progressive disease19217181
  Not evaluated112992
RR (%) (95% CI)61.2 (53.0 - 69.0)72.2 (58.4 - 83.5)55.1 (44.7 - 65.2)0.05554.3 (44.3 - 64.0)76.6 (62.0 - 87.7)0.01
DCR (%) (95% CI)80.3 (73.0 - 86.3)92.6 (82.1- 97.9)73.5 (63.6 - 81.9)< 0.0174.3 (64.8 - 82.3)93.6 (82.5 - 98.7)< 0.01

 

Table 3. Univariate Cox Hazard Analyses of Factors Associated With Overall Survival and Progression-Free Survival
 
OSPFS
HR95% CIPHR95% CIP
Afa: afatinib; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; del: deletion; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor- tyrosine kinase inhibitor; Erl: erlotinib; Gef: gefinitib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression-free survival.
Age (years < 75 vs. ≥ 75)1.180.75 - 1.850.480.970.67 - 1.410.88
Sex (female vs. male)1.330.86 - 2.070.191.170.81 - 1.680.41
Distant metastasis (no vs. yes)2.080.99 - 4.380.0542.101.12 - 3.930.02
ECOG PS (0 - 1 vs. 2 - 4)4.082.56 - 6.50< 0.011.981.33 - 2.93< 0.01
BMI (≥ 18.5 vs. < 18.5)1.580.95 - 2.640.081.601.04 - 2.470.03
EGFR mutation (exon 19 del vs. others)1.270.82 - 1.950.291.140.79 - 1.630.49
EGFR-TKI line (first vs. second or later)1.460.94 - 2.260.091.471.01 - 2.150.04
EGFR-TKI (Gef vs. Erl or Afa)0.840.50 - 1.410.510.610.40 - 0.920.02
Hemoglobin (g/dL)0.890.77 - 1.020.090.940.85 - 1.050.29
Ccr (mL/min) (/10)0.860.74 - 0.9980.0470.880.78 - 0.990.04
Sodium (mEq/L) (/10)0.190.10 - 0.39< 0.010.340.19 - 0.62< 0.01
LDH (IU/L) (/100)1.361.19 - 1.54< 0.011.241.11 - 1.39< 0.01
CRP (mg/dL)1.171.08 - 1.27< 0.011.191.10 - 1.29< 0.01
NLR1.121.07 - 1.18< 0.011.081.03 - 1.13< 0.01
LMR0.780.69 - 0.89< 0.010.890.81 - 0.980.02

 

Table 4. Multivariate Cox Hazard Analyses of Factors Associated With Overall Survival
 
NLRLMR
HR95% CIPHR95% CIP
BMI: body mass index; Ccr: creatinine clearance: CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.
Distant metastasis (no vs. yes)1.590.73 - 3.500.251.440.64 - 3.240.38
ECOG PS (0 - 1 vs. 2 - 4)3.462.03 - 5.89< 0.013.411.99 - 5.82< 0.01
BMI (≥ 18.5 vs. < 18.5)1.620.89 - 2.930.121.580.87 - 2.870.14
EGFR-TKI line (first vs. second or later)1.71.1.07 - 2.730.021.721.08 - 2.740.02
Hemoglobin (g/dL)1.140.97 - 1.340.111.150.98 - 1.360.08
Ccr (mL/min) (/10)0.860.73 - 1.020.080.860.73 - 1.010.07
Sodium (mEq/L) (/10)0.300.13 - 0.71< 0.010.270.11 - 0.64< 0.01
LDH (IU/L) (/100)1.241.05 - 1.480.011.271.07 - 1.50< 0.01
CRP (mg/dL)1.010.90 - 1.140.820.980.86 - 1.110.74
NLR1.071.01 - 1.140.03---
LMR---0.880.76 - 1.010.07

 

Table 5. Multivariate Cox Hazard Analyses of Factors Associated With Progression-Free Survival
 
NLRLMR
HR95% CIPHR95% CIP
Afa: afatinib; ALP: alkaline phosphatase; BMI: body mass index; Ccr: creatinine clearance; CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitors; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio.
Distant metastasis (no vs. yes)1.690.87 - 3.270.121.770.92 - 3.420.09
ECOG PS (0 - 1 vs. 2 - 4)1.550.97 - 2.470.071.631.01 - 2.610.04
BMI (≥ 18.5 vs. < 18.5)1.530.94 - 2.470.091.570.96 - 2.550.07
EGFR-TKI line (first vs. second or later)1.470.99 - 2.190.0581.491.00 - 2.230.049
EGFR-TKI (Gef vs. Erl or Afa)0.630.40 - 0.990.0460.640.41 - 1.010.06
Ccr (mL/min) (/10)0.940.82 - 1.080.370.940.82 - 1.070.36
Sodium (mEq/L) (/10)0.600.30 - 1.200.150.600.30 - 1.210.16
LDH (IU/L) (/100)1.110.97 - 1.270.151.120.98 - 1.290.10
CRP (mg/dL)1.100.99 - 1.220.081.100.99 - 1.230.07
NLR1.030.97 - 1.100.29---
LMR---1.000.90 - 1.120.99

 

Table 6. Review of Previous Studies of Multivariate Analyses for Prediction of Survival Outcomes in Patients With EGFR Mutant NSCLC
 
Author (year)CountryNTreatmentVariableMultivariate analyses
Cut-offOSPFS
HR (95% CI)PHR (95% CI)P
CI: confidence interval; Erl: erlotinib; Gef: gefitinib; HR: hazard ratio; NA: not assessed; LMR: lymphocyte-to-monocyte ratio; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression free survival.
Lin et al [27] (2014)China81Gef (30%) Erl (70%) All first-lineNLR3.53.29 (1.62 - 6.71)< 0.0013.89 (1.98 - 7.68)< 0.001
Chen et al [30] (2015)Taiwan253All first-lineLMR3.292.36 (1.66 - 3.35)< 0.0011.71 (1.14 - 2.56)0.009
Sim et al [29] (2016)Korea85All first-lineNLR3NANA1.239 (0.693 - 2.215)0.469
Meriggi et al [28] (2017)Italy63Gef (71%) Erl (29%)NLR3.52.699 (1.187 - 6.137)0.0182.275 (1.257 - 4.116)0.007
Ding et al [26] (2017)Australia85First-line (85%)NLR50.43 (0.19 - 0.94)0.040.40 (0.18 - 0.87)0.02
OursJapan152Gef (70%) Erl (24%) First-line (68%)NLR-1.07 (1.01 - 1.14)0.031.03 (0.97 - 1.10)0.29
LMR-0.88 (0.76 - 1.01)0.071.00 (0.90 - 1.12)0.99