J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 10, Number 8, August 2018, pages 657-664

Pretreatment Lymphocyte to Monocyte Ratio as a Prognostic Marker for Advanced Pulmonary Squamous Cell Carcinoma Treated With Chemotherapy

Figure 1. Hazard ratios and cutoff points of LMR and NLR for overall survival of patients with pulmonary squamous cell carcinoma. (a) LMR; (b) NLR. The plots were determined using Cutoff Finder. The vertical lines are the optimal cutoff points providing the most significant split (log-rank test). LMR: lymphocyte to monocyte ratio; NLR: neutrophil to lymphocyte ratio; HR: hazard ratio; OS: overall survival.

Figure 2. Kaplan-Meier survival curves of overall survival according to LMR, NLR and mGPS. (a) LMR; (b) NLR; (c) mGPS. LMR: lymphocyte to monocyte ratio; mGPS: modified Glasgow prognostic score; NLR: neutrophil to lymphocyte ratio.

**Table 1.** Backgrounds and Laboratory Data at the Start of First-Line Chemotherapy
	All	LMR	P	NLR	P	mGPS	P
^amean ± SD; ^bMann-Whitney test; ^cFisher’s exact test. Alb: albumin; ALP: alkaline phosphatase; BMI: body mass index; Ccr: creatinine clearance; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; Hb: hemoglobin; LDH: lactate dehydrogenase; LMR: lymphocyte to monocyte ratio; Lym: lymphocyte; Mono: monocyte; mGPS: modified Glasgow prognostic score; Neu: neutrophil; NLR: neutrophil to lymphocyte ratio; SD: standard deviation.
N	107	24	83		82	25		69	38
Background
Age (years)^a	70.2 ± 8.2	69.4 ± 9.4	70.5 ± 7.8	0.66^b	70.8 ± 7.9	68.4 ± 8.9	0.16^b	69.9 ± 8.8	70.9 ± 7.0	0.87^b
< 75/≥ 75 years	68/39	15/9	53/30	1.00^c	50/32	18/7	0.35^c	42/27	26/12	0.53^c
Sex (N)
Male/female	82/25	18/6	64/19	0.79^c	63/19	19/6	1.00^c	50/19	32/6	0.23^c
Stage (N)
IIIB/IV/rec	41/56/10	7/15/2	34/41/8	0.54^c	35/37/10	6/19/0	0.02^c	23/37/9	18/19/1	0.13^c
ECOG PS (N)
0 - 1/2/3 - 4	81/22/4	16/8/0	65/14/4	0.17^c	70/10/2	11/12/2	< 0.01^c	55/13/1	26/9/2	0.30^c
BMI^a	21.3 ± 3.2	20.5 ± 2.9	21.5 ± 3.3	0.24^b	21.4 ± 3.2	20.7 ± 3.2	0.34^b	21.4 ± 3.0	21.0 ± 3.6	0.29^b
< 18.5/≥ 18.5	21/86	6/18	15/68	0.56 ^c	16/66	5/20	1.00^c	56/13	30/8	0.80^c
Laboratory data^a
Neu (cells/µL)	6,069 ± 2,818	7,698 ± 3,344	5,598 ± 2,475	< 0.01^b	5,045 ± 1,625	9,428 ± 3,289	< 0.01^b	5,425 ± 2,518	7,238 ± 2,986	< 0.01^b
Lym (cells/µL)	1,636 ± 659	1,136± 388	1,781 ± 652	< 0.01^b	1,771 ± 658	1,195 ± 441	< 0.01^b	1,725 ± 682	1,475 ± 591	0.04^b
Mono (cells/µL)	560 ± 227	791 ± 282	493 ± 155	< 0.01^b	512 ± 184	719 ± 281	< 0.01^b	512 ± 219	648 ± 217	< 0.01^b
NLR	4.31 ± 2.92	7.47 ± 4.11	3.40 ± 1.59	< 0.01^b	3.06 ± 1.01	8.40 ± 3.39	< 0.01^b	3.60 ± 2.55	5.60 ± 3.14	< 0.01^b
LMR	3.31 ± 1.75	1.52 ± 0.47	3.82 ± 1.64	< 0.01^b	3.75 ± 1.72	1.86 ± 0.83	< 0.01^b	3.78 ± 1.89	2.45 ± 1.03	< 0.01^b
Hb (g/dL)	12.0 ± 1.9	11.0 ± 1.9	12.2 ± 1.8	0.01^b	12.1 ± 1.8	11.4 ± 2.1	0.12^b	12.5 ± 1.7	10.9 ± 1.8	< 0.01^b
Sodium (mEq/L)	138.3 ± 3.2	136.9 ± 4.0	138.8 ± 2.9	0.01^b	138.9 ± 2.7	136.4 ± 4.1	< 0.01^b	138.5 ± 2.7	138.0 ± 4.0	0.61^b
Ccr (mL/min)	55.1 ± 14.9	52.8 ± 13.6	55.8 ± 15.2	0.58^b	54.7 ± 15.0	56.6 ± 14.5	0.42^b	56.3 ± 16.6	53.1 ± 11.1	0.55^b
LDH (IU/L)	225.7 ± 136.0	283.3 ± 258.2	209.0 ± 62.9	0.19^b	229.2 ± 152.8	214.0 ± 51.9	0.57^b	234.3 ± 155.4	210.0 ± 90.5	0.14^b
ALP (IU/L)	292.0 ± 152.4	344.6 ± 165.7	276.8 ± 145.9	0.02^b	279.8 ± 148.0	332.1 ± 162.7	0.048^b	282.5 ± 115.2	309.3 ± 204.2	0.18^b
Alb (g/dL)	3.4 ± 0.6	3.2 ± 0.6	3.5 ± 0.5	< 0.01^b	3.6 ± 0.5	3.1 ± 0.6	< 0.01^b	3.7 ± 0.4	2.9 ± 0.5	< 0.01^b
CRP (mg/dL)	3.7 ± 4.4	7.3 ± 6.2	2.6 ± 3.1	< 0.01^b	2.5 ± 3.0	7.5 ± 5.9	< 0.01^b	1.7 ± 2.3	7.3 ± 4.9	< 0.01^b
mGPS
0/1/2	39/30/38	4/7/13	35/23/25	0.04^c	36/24/22	3/6/16	< 0.01^c	-	-	-

Table 1. Backgrounds and Laboratory Data at the Start of First-Line Chemotherapy

All

LMR

NLR

mGPS

< 2.07

≥ 2.07

< 5.28

≥ 5.28

0 - 1

^amean ± SD; ^bMann-Whitney test; ^cFisher’s exact test. Alb: albumin; ALP: alkaline phosphatase; BMI: body mass index; Ccr: creatinine clearance; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; Hb: hemoglobin; LDH: lactate dehydrogenase; LMR: lymphocyte to monocyte ratio; Lym: lymphocyte; Mono: monocyte; mGPS: modified Glasgow prognostic score; Neu: neutrophil; NLR: neutrophil to lymphocyte ratio; SD: standard deviation.

107

Background

Age (years)^a

70.2 ± 8.2

69.4 ± 9.4

70.5 ± 7.8

0.66^b

70.8 ± 7.9

68.4 ± 8.9

0.16^b

69.9 ± 8.8

70.9 ± 7.0

0.87^b

< 75/≥ 75 years

68/39

15/9

53/30

1.00^c

50/32

18/7

0.35^c

42/27

26/12

0.53^c

Sex (N)

Male/female

82/25

18/6

64/19

0.79^c

63/19

19/6

1.00^c

50/19

32/6

0.23^c

Stage (N)

IIIB/IV/rec

41/56/10

7/15/2

34/41/8

0.54^c

35/37/10

6/19/0

0.02^c

23/37/9

18/19/1

0.13^c

ECOG PS (N)

0 - 1/2/3 - 4

81/22/4

16/8/0

65/14/4

0.17^c

70/10/2

11/12/2

< 0.01^c

55/13/1

26/9/2

0.30^c

BMI^a

21.3 ± 3.2

20.5 ± 2.9

21.5 ± 3.3

0.24^b

21.4 ± 3.2

20.7 ± 3.2

0.34^b

21.4 ± 3.0

21.0 ± 3.6

0.29^b

< 18.5/≥ 18.5

21/86

6/18

15/68

0.56 ^c

16/66

5/20

1.00^c

56/13

30/8

0.80^c

Laboratory data^a

Neu (cells/µL)

6,069 ± 2,818

7,698 ± 3,344

5,598 ± 2,475

< 0.01^b

5,045 ± 1,625

9,428 ± 3,289

< 0.01^b

5,425 ± 2,518

7,238 ± 2,986

< 0.01^b

Lym (cells/µL)

1,636 ± 659

1,136± 388

1,781 ± 652

< 0.01^b

1,771 ± 658

1,195 ± 441

< 0.01^b

1,725 ± 682

1,475 ± 591

0.04^b

Mono (cells/µL)

560 ± 227

791 ± 282

493 ± 155

< 0.01^b

512 ± 184

719 ± 281

< 0.01^b

512 ± 219

648 ± 217

< 0.01^b

NLR

4.31 ± 2.92

7.47 ± 4.11

3.40 ± 1.59

< 0.01^b

3.06 ± 1.01

8.40 ± 3.39

< 0.01^b

3.60 ± 2.55

5.60 ± 3.14

< 0.01^b

LMR

3.31 ± 1.75

1.52 ± 0.47

3.82 ± 1.64

< 0.01^b

3.75 ± 1.72

1.86 ± 0.83

< 0.01^b

3.78 ± 1.89

2.45 ± 1.03

< 0.01^b

Hb (g/dL)

12.0 ± 1.9

11.0 ± 1.9

12.2 ± 1.8

0.01^b

12.1 ± 1.8

11.4 ± 2.1

0.12^b

12.5 ± 1.7

10.9 ± 1.8

< 0.01^b

Sodium (mEq/L)

138.3 ± 3.2

136.9 ± 4.0

138.8 ± 2.9

0.01^b

138.9 ± 2.7

136.4 ± 4.1

< 0.01^b

138.5 ± 2.7

138.0 ± 4.0

0.61^b

Ccr (mL/min)

55.1 ± 14.9

52.8 ± 13.6

55.8 ± 15.2

0.58^b

54.7 ± 15.0

56.6 ± 14.5

0.42^b

56.3 ± 16.6

53.1 ± 11.1

0.55^b

LDH (IU/L)

225.7 ± 136.0

283.3 ± 258.2

209.0 ± 62.9

0.19^b

229.2 ± 152.8

214.0 ± 51.9

0.57^b

234.3 ± 155.4

210.0 ± 90.5

0.14^b

ALP (IU/L)

292.0 ± 152.4

344.6 ± 165.7

276.8 ± 145.9

0.02^b

279.8 ± 148.0

332.1 ± 162.7

0.048^b

282.5 ± 115.2

309.3 ± 204.2

0.18^b

Alb (g/dL)

3.4 ± 0.6

3.2 ± 0.6

3.5 ± 0.5

< 0.01^b

3.6 ± 0.5

3.1 ± 0.6

< 0.01^b

3.7 ± 0.4

2.9 ± 0.5

< 0.01^b

CRP (mg/dL)

3.7 ± 4.4

7.3 ± 6.2

2.6 ± 3.1

< 0.01^b

2.5 ± 3.0

7.5 ± 5.9

< 0.01^b

1.7 ± 2.3

7.3 ± 4.9

< 0.01^b

mGPS

0/1/2

39/30/38

4/7/13

35/23/25

0.04^c

36/24/22

3/6/16

< 0.01^c

**Table 2.** Treatment and Efficacy
	LMR	P	NLR	P	mGPS	P
aFisher’s exact test; ^blog-rank test. CBDCA: carboplatin; CDDP: cisplatin; CI: confidence interval; DCR; disease control rate; ICI: immuno-checkpoint inhibitor; LMR: lymphocyte to monocyte ratio; mGPS: modified Glasgow prognostic score; nab-PTX: albumin-bound paclitaxel; NLR: neutrophil to lymphocyte ratio; PFS: progression-free survival; PTX: paclitaxel; RR: response rate; TRT: thoracic radiotherapy.
N	24	83		82	25		69	38
First-line regimen
Single or combination (N)
Single/combination	1/23	9/74	0.45^a	8/74	2/23	1.00^a	6/63	4/34	0.74^a
Platinum-based (N)
CBDCA-based	21	71	1.00^a	72	20	0.34^a	61	31	0.39^a
CDDP-based	2	3	0.31^a	2	3	0.08^a	2	3	0.35^a
PTX-containing (N)	9	34	0.82^a	33	10	1.00^a	29	14	0.68^a
nab-PTX-containing (N)	8	19	0.30^a	19	8	0.43^a	16	11	0.64^a
S-1 containing (N)	5	24	0.60^a	25	4	0.20^a	19	10	1.00^a

Concurrent TRT (N)	2	9	1.00^a	7	4	0.28^a	6	5	0.52^a
First-line response
RR (%) (95% CI)	20.8 (7.1 - 42.2)	48.2 (37.1 - 59.4)	0.02^a	47.6 (36.4 - 58.9)	24.0 (9.4 - 45.1)	0.04^a	43.5 (31.6 - 56.0)	39.5 (24.0 - 56.6)	0.84^a
DCR (%) (95% CI)	54.2 (32.8 - 74.4)	68.7 (57.6 - 78.4)	0.23^a	69.5 (58.4 - 79.2)	52.0 (31.3 - 72.2)	0.15^a	66.7 (54.3 - 77.6)	63.2 (46.0 - 78.2)	0.83^a
PFS (months) (95% CI)	2.4 (1.7 - 5.4)	5.1 (4.0 - 6.5)	<0.01^b	5.1 (4.1 - 6.5)	2.4 (1.9 - 5.3)	0.02^b	4.8 (3.7 - 5.9)	4.2 (3.1 - 6.5)	0.32^b
Second or further line (N)	9	55	0.02^a	54	10	0.03^a	45	19	0.15^a
ICI (N)	1	2	0.54^a	3	0	1.0	3	0	0.551

Table 2. Treatment and Efficacy

LMR

NLR

mGPS

< 2.07

≥ 2.07

< 5.28

≥ 5.28

0 - 1

aFisher’s exact test; ^blog-rank test. CBDCA: carboplatin; CDDP: cisplatin; CI: confidence interval; DCR; disease control rate; ICI: immuno-checkpoint inhibitor; LMR: lymphocyte to monocyte ratio; mGPS: modified Glasgow prognostic score; nab-PTX: albumin-bound paclitaxel; NLR: neutrophil to lymphocyte ratio; PFS: progression-free survival; PTX: paclitaxel; RR: response rate; TRT: thoracic radiotherapy.

First-line regimen

Single or combination (N)

Single/combination

1/23

9/74

0.45^a

8/74

2/23

1.00^a

6/63

4/34

0.74^a

Platinum-based (N)

CBDCA-based

1.00^a

0.34^a

0.39^a

CDDP-based

0.31^a

0.08^a

0.35^a

PTX-containing (N)

0.82^a

1.00^a

0.68^a

nab-PTX-containing (N)

0.30^a

0.43^a

0.64^a

S-1 containing (N)

0.60^a

0.20^a

1.00^a

Concurrent TRT (N)

1.00^a

0.28^a

0.52^a

First-line response

RR (%) (95% CI)

20.8 (7.1 - 42.2)

48.2 (37.1 - 59.4)

0.02^a

47.6 (36.4 - 58.9)

24.0 (9.4 - 45.1)

0.04^a

43.5 (31.6 - 56.0)

39.5 (24.0 - 56.6)

0.84^a

DCR (%) (95% CI)

54.2 (32.8 - 74.4)

68.7 (57.6 - 78.4)

0.23^a

69.5 (58.4 - 79.2)

52.0 (31.3 - 72.2)

0.15^a

66.7 (54.3 - 77.6)

63.2 (46.0 - 78.2)

0.83^a

PFS (months) (95% CI)

2.4 (1.7 - 5.4)

5.1 (4.0 - 6.5)

<0.01^b

5.1 (4.1 - 6.5)

2.4 (1.9 - 5.3)

0.02^b

4.8 (3.7 - 5.9)

4.2 (3.1 - 6.5)

0.32^b

Second or further line (N)

0.02^a

0.03^a

0.15^a

ICI (N)

0.54^a

1.0

0.551

**Table 3.** Univariate Cox Proportional Hazard Analysis of Factors Associated With Overall Survival
	HR	95% CI	P
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; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte to monocyte ratio; mGPS: modified Glasgow prognostic score; NLR: neutrophil to lymphocyte ratio.
Age (years)
< 75 versus ≥ 75	1.20	0.75 - 1.93	0.45
Sex
Female versus male	1.62	0.90 - 2.91	0.11
Distant metastasis
No versus yes	1.47	0.92 - 2.37	0.11
ECOG PS
0 - 1 versus 2 - 4	2.92	1.76 - 4.86	< 0.01
BMI
≥ 18.5 versus < 18.5	1.42	0.80 - 2.52	0.23
Hemoglobin (g/dL)	0.96	0.85 - 1.09	0.55
Ccr (mL/min) (/10)	1.02	0.88 - 1.18	0.81
Sodium (mEq/L) (/10)
≥ 135 versus < 135	0.91	0.45 - 1.82	0.78
LDH (IU/L) (/100)	1.03	0.85 - 1.23	0.80
ALP (IU/L) (/100)	1.05	0.90 - 1.21	0.55
Albumin (g/dL)	0.72	0.49 - 1.07	0.10
CRP (mg/dL)	1.09	1.03 - 1.15	< 0.01
NLR
< 5.28 versus ≥ 5.28	2.80	1.62 - 4.83	< 0.01
LMR
≥ 2.07 versus < 2.07	8.00	0.18 - 0.54	< 0.01
mGPS
0,1 versus 2	1.14	0.70 - 1.85	0.61

Table 3. Univariate Cox Proportional Hazard Analysis of Factors Associated With Overall Survival

95% CI

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; HR: hazard ratio; LDH: lactate dehydrogenase; LMR: lymphocyte to monocyte ratio; mGPS: modified Glasgow prognostic score; NLR: neutrophil to lymphocyte ratio.

Age (years)

< 75 versus ≥ 75

1.20

0.75 - 1.93

0.45

Sex

Female versus male

1.62

0.90 - 2.91

0.11

Distant metastasis

No versus yes

1.47

0.92 - 2.37

0.11

ECOG PS

0 - 1 versus 2 - 4

2.92

1.76 - 4.86

< 0.01

BMI

≥ 18.5 versus < 18.5

1.42

0.80 - 2.52

0.23

Hemoglobin (g/dL)

0.96

0.85 - 1.09

0.55

Ccr (mL/min) (/10)

1.02

0.88 - 1.18

0.81

Sodium (mEq/L) (/10)

≥ 135 versus < 135

0.91

0.45 - 1.82

0.78

LDH (IU/L) (/100)

1.03

0.85 - 1.23

0.80

ALP (IU/L) (/100)

1.05

0.90 - 1.21

0.55

Albumin (g/dL)

0.72

0.49 - 1.07

0.10

CRP (mg/dL)

1.09

1.03 - 1.15

< 0.01

NLR

< 5.28 versus ≥ 5.28

2.80

1.62 - 4.83

< 0.01

LMR

≥ 2.07 versus < 2.07

8.00

0.18 - 0.54

< 0.01

mGPS

0,1 versus 2

1.14

0.70 - 1.85

0.61

**Table 4.** Multivariate Cox Proportional Hazard Analysis of Factors Associated With Overall Survival
	HR	95% CI	P
CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; HR: hazard ratio; LMR: lymphocyte to monocyte ratio; NLR: neutrophil to lymphocyte ratio.
Sex
Female versus male	1.32	0.71 - 2.43	0.38
Distant metastasis
No versus yes	1.54	0.90 - 2.60	0.11
ECOG PS
0 - 1 versus 2 - 4	3.09	1.77 - 5.40	< 0.01
Albumin (g/dL)	1.24	0.76 - 2.04	0.39
CRP (mg/dL)	1.03	0.96 - 1.10	0.42
NLR
< 5.28 versus ≥ 5.28	1.37	0.67 - 2.79	0.39
LMR
< 2.07 versus ≥ 2.07	0.41	0.21 - 0.79	< 0.01

Table 4. Multivariate Cox Proportional Hazard Analysis of Factors Associated With Overall Survival

95% CI

CI: confidence interval; CRP: C-reactive protein; ECOG PS: Eastern Cooperative Oncology Group performance status; HR: hazard ratio; LMR: lymphocyte to monocyte ratio; NLR: neutrophil to lymphocyte ratio.

Sex

Female versus male

1.32

0.71 - 2.43

0.38

Distant metastasis

No versus yes

1.54

0.90 - 2.60

0.11

ECOG PS

0 - 1 versus 2 - 4

3.09

1.77 - 5.40

< 0.01

Albumin (g/dL)

1.24

0.76 - 2.04

0.39

CRP (mg/dL)

1.03

0.96 - 1.10

0.42

NLR

< 5.28 versus ≥ 5.28

1.37

0.67 - 2.79

0.39

LMR

< 2.07 versus ≥ 2.07

0.41

0.21 - 0.79

< 0.01