The prognostic impact of neutrophil to lymphocyte ratio in advanced non-small cell lung cancer patients treated with EGFR TKI

Figures & data

Table 1 Patient characteristics

Characteristics	Total	NLR<2.96		NLR≥2.96		P-value
		MLR<0.38	MLR≥0.38	MLR<0.38	MLR≥0.38
Number of patients	112	29	7	22	54
Age, years						0.096a
<59	50	14	4	5	27
≥59	62	15	3	17	27
Gender						0.872a
Female	61	14	4	13	30
Male	51	15	3	9	24
ECOG PS						0.183a
0–1	95	27	7	16	45
2–3	17	2	0	6	9
Number of distant metastasis						0.734a
0–1	23	7	1	4	11
≥2	89	22	6	18	43
Brain metastasis						0.448a
No	81	22	7	15	37
Yes	31	7	0	7	17
Pleural effusion						0.371a
No	80	24	5	14	37
Yes	32	5	2	8	17
Tumor size						0.005a
≤3cm	25	13	2	4	6
>3cm	87	16	5	18	48
<b>EGFR mutation type						0.460a
E19del	77	23	5	13	36
L858R	35	6	2	9	18
EGFR TKI treatment						0.489a
First line	89	22	6	20	41
Second/third line	23	7	1	2	13
EGFR TKI type						0.140a
Erlotinib	97	23	7	17	50
Gefitinib	15	6	0	5	4
Clinical response						0.268a
PR+SD	59	16	3	15	25
PD	53	13	4	7	29
Laboratory data
NEU, 10^9/L (95% CI)	5.99 (5.45–7.10)	4.80 (3.75–5.45)	2.53 (1.65–4.77)	7.81 (6.21–9.20)	7.55 (5.97–9.31)	<0.001b
LYM, 10^9/L (95% CI)	1.69 (1.45–1.95)	2.19 (1.97–2.37)	1.29 (0.86–2.28)	1.96 (1.69–2.28)	1.29 (1.08–1.53)	<0.001b
MONO, 10^9/L (95% CI)	0.62 (0.56–0.69)	0.57 (0.45–0.68)	0.64 (0.38–0.89)	0.57 (0.46–0.66)	0.71 (0.60–0.76)	0.025b

Notes:

a Fisher’s exact test.

b Kruskal–Wallis rank test.

Abbreviations: NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; PR, partial response; SD, stable disease; PD, progressive disease; NEU, neutrophil; LYM, lymphocyte; MONO, monocyte, TKI, tyrosine kinase inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status.

Table 2 Inflammatory index values in NSCLC at different stages and in control group

Parameter	NSCLC			Control (n=112)	P-value
	Baseline (n=112)	After 3 months of treatment (n=112)	Progressive disease (n=53)
WBC, 10^9/L	9.4	7.1	9.8	7.1	<0.001a
(95% CI)	(8.6–10.3)	(6.6–7.5)	(8.4–11.2)	(6.6–7.6)	0.588b
PLT, 10^9/L	289.9	273.4	271.7	240.7	0.458a
(95% CI)	(266.3–313.5)	(255.7–291.2)	(248.8–294.5)	(230.6–250.8)	0.006b
NLR	4.90	2.02	5.51	1.72	<0.001a
(95% CI)	(4.11–5.68)	(1.84–2.20)	(4.16–6.85)	(1.55–1.90)	0.001b
MLR	0.44	0.28	0.51	0.20	<0.001a
(95% CI)	(0.39–0.49)	(0.26–0.31)	(0.45–0.57)	(0.18–0.22)	0.003b
PLR	213.9	143.2	210.3	108.8	<0.001a
(95% CI)	(181.9–245.9)	(131.3–155.1)	(171.6–248.9)	(101.9–115.7)	0.002b

Notes:

a At baseline vs posttreatment and progressive disease stage.

b In NSCLC after treatment vs in control.

Abbreviations: NSCLC, non-small cell lung cancer; WBC, white blood cell; PLT, platelet; NLR, neutrophil to lymphocyte ratio; MLR; monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio.

Figure 1 Comparison of area under the ROC curve of inflammatory markers in response evaluation.

Abbreviations: WBC, white blood cell; PLT, platelet; NLR, neutrophil to lymphocyte ratio, MLR, monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio; ROC, receiver operating characteristic.

Table 3 Optimal cutoff point of each study marker, sensitivity, specificity and AUC values in predicting response to EGFR TKI

Parameter	Cutoff	Sensitivity, % (95% CI)	Specificity,% (95% CI)	AUC, % (95% CI)
WBC, 10^9/L	9.0	48.2	78.4	0.699
		(37.3–59.3)	(69.2–86.0)	(0.623–0.775)
PLT, 10^9/L	324.0	32.9	77.5	0.548
		(23.1–44.0)	(68.1–85.1)	(0.464–0.632)
NLR	2.96	71.8	90.2	0.873
		(60.5–81.4)	(82.6–95.5)	(0.821–0.926)
MLR	0.38	54.1	86.3	0.762
		(44.7–67.6)	(77.5–92.4)	(0.691–0.832)
PLR	189.8	49.4	78.4	0.689
		(38.4–60.5)	(69.2–86.0)	(0.613–0.766)

Abbreviations: AUC, area under the curve; WBC, white blood cell; PLT, platelet; NLR, neutrophil to lymphocyte ratio, MLR, monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio; TKI, tyrosine kinase inhibitor.

Table 4 Estimation of PFS and prognosis markers for NSCLC patients

Parameters	PFS (95% CI)	Univariate analysis		Multivariate analysis
		HR (95% CI)	P-value	HR (95% CI)	P-value
Age, years		0.96 (0.55–1.68)	0.897	–	–
<59	9.0 (7.5–11.3)
≥59	8.8 (7.7–13.0)
Gender		1.13 (0.65–1.98)	0.658	–	–
Female	8.8 (7.5–12.0)
Male	9.0 (7.9–11.3)
ECOG PS		1.91 (0.84–4.33)	0.121	–	–
0–1	9.0 (8.0–11.3)
2–3	7.9 (3.2–11.1)
Number of distant metastasis		2.01 (0.79–5.10)	0.142	–	–
0–1	10.4 (5.8–12.1)
≥2	8.8 (7.9–11.0)
Brain metastasis		1.56 (0.84–2.91)	0.160	–	–
No	9.2 (7.9–12.0)
Yes	8.0 (6.2–11.0)
Pleural effusion		1.55 (0.81–2.98)	0.191	–	–
No	9.2 (8.0–11.3)
Yes	7.7 (3.1–12.2)
Tumor size		2.24 (1.04–4.83)	0.039	–	–
≤3 cm	13.6 (5.8–23.3)
>3 cm	8.2 (7.5–10.4)
EGFR mutation type		0.84 (0.49–1.46)	0.546	–	–
E19del	9.0 (7.7–12.2)
L858R	8.0 (6.2–11.1)
EGFR TKI treatment		0.96 (0.61–1.79)	0.802	–	–
First line	8.8 (7.5–11.0)
Second/third line	10.4 (7.5–13.8)
EGFR TKI type		0.43 (0.28–1.02)	0.506	–	–
Erlotinib	8.2 (7.7–10.4)
Gefitinib	11.0 (5.5–23.3)
WBC, 10^9/L		1.65 (0.92–2.96)	0.325	–	–
<9.0	9.3 (7.9–11.2)
≥9.0	8.0 (7.1–9.9)
PLT, 10^9/L		0.92 (0.50–1.72)	0.612	–	–
<324.0	9.0 (7.9–10.0)
≥324.0	8.0 (6.9–14.0)
NLR		2.67 (1.41–5.03)	0.006	2.15 (1.15–3.99)	0.016
<2.96	11.1 (9.5–13.9)
≥2.96	7.7 (6.0–8.1)
MLR		1.91 (1.07–3.41)	0.034	–	–
<0.38	10.1 (9.0–13.0)
≥0.38	7.5 (5.9–8.4)
PLR		1.09 (0.62–1.92)	0.764	–	–
<189.8	9.1 (8.0–10.4)
≥189.8	7.9 (5.4–10.7)

Abbreviations: PFS, progression-free survival; NSCLC, non-small cell lung cancer; WBC, white blood cell; PLT, platelet; NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; PLR, platelet to lymphocyte ratio; TKI, tyrosine kinase inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status.

Figure 2 Progression-free survival of NSCLC patients according to the tumor size (A), the pretreatment levels of NLR (B), and MLR (C).

Abbreviations: NLR, neutrophil to lymphocyte ratio; MLR, monocyte to lymphocyte ratio; NSCLC, non-small cell lung cancer.