Clinical significance of neutrophil-to-lymphocyte ratio in predicting prognosis of advanced lung cancer patients receiving immunotherapy combined with chemotherapy

doi:10.3877/cma.j.issn.1674-6902.2026.04.012

Abstract

Abstract:

Objective

To explore predictive biomarkers for the efficacy of firstline immune checkpoint inhibitors (ICIs) combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a prognostic scoring model.

Methods

A total of 125 patients with advanced NSCLC who received firstline ICIs plus chemotherapy in our hospital from October 2023 to October 2025 were enrolled, and treatment responses were analyzed. Variables were screened by LASSO regression, and the NLAL scoring system was constructed based on neutrophiltolymphocyte ratio (NLR), lactate dehydrogenase (LDH), albumin (ALB), and liver metastasis. Patients were divided into a lowrisk group (0-1 point, 95 cases) and a highrisk group (2–5 points, 30 cases). Patients were divided into the observation group (NLR>3.25) and the control group (NLR<3.25). Progressionfree survival (PFS) was analyzed using receiver operating characteristic (ROC) curves, multivariate Cox proportional hazards regression, and KaplanMeier curves.

Results

The disease control rate (DCR) in the lowrisk group was 84.21%, significantly higher than that in the highrisk group (60.00%) (χ²=7.892, P=0.005); the objective response rate (ORR) was also higher in the lowrisk group [40.00% (38/95) vs. 10.00% (3/30), χ²=9.310, P=0.002]. The area under the curve (AUC) of the NLAL score for predicting DCR was 0.797 (95%CI: 0.665~0.872), which was superior to single indicators including NLR (AUC=0.735), LDH (AUC=0.752), ALB (AUC=0.718), liver metastasis (AUC=0.689), and PDL1 expression (AUC=0.578) (all P<0.05). Multivariate Cox regression showed that liver metastasis (HR=1.524, 95%CI: 1.032~2.248, P=0.034), NLR>3.25 (HR=1.854, 95%CI: 1.247~2.766, P=0.003), LDH>225 U/L (HR=1.654, 95%CI: 1.114~2.452, P=0.013), and ALB<36.52 g/L(HR=1.416, 95%CI: 1.005~1.996, P=0.046) were risk factors for shorter PFS. The median PFS was longer in the lowrisk group than in the highrisk group (15.31 months vs. 6.78 months, logrank P<0.001). The AUC of the NLAL score for predicting PFS was 0.763 (95%CI: 0.689~0.821), superior to single indicators (P<0.05). With a median followup of 19 months, 72 patients (57.60%) survived and 53 (42.40%) died.

Conclusion

The NLAL score based on NLR, LDH, ALB, and liver metastasis can predict ORR, DCR, and PFS in advanced NSCLC patients receiving firstline ICIs combined with chemotherapy, and it is superior to single peripheral blood biomarkers and PDL1 expression, demonstrating clinical utility.

Key words: Nonsmall cell lung cancer, Immune checkpoint inhibitors, Chemotherapy, Neutrophiltolymphocyte ratio, Lactate dehydrogenase, Prognosis

Yue Chen, Binglin Wu, Nina Feng, Qinqin Yang, Xiongwei Miao, Miaomiao Shang, Qiaowei Ren. Clinical significance of neutrophil-to-lymphocyte ratio in predicting prognosis of advanced lung cancer patients receiving immunotherapy combined with chemotherapy[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(04): 607-614.

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References 30

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临床资料	观察组(n＝51)	对照组(n＝74)	t/χ²值	P值
吸烟史	32(62.75)	52(70.27)	0.776	0.379
临床分期			8.677	0.003
Ⅲ期	5(9.80)	24(32.43)
Ⅳ期	46(90.20)	50(67.57)
ICIs类型			0.332	0.565
PD-1抑制剂	44(86.27)	61(82.43)
PD-L1抑制剂	7(13.73)	13(17.57)
化疗方案			0.243	0.622
培美曲塞	33(64.71)	51(68.92)
白蛋白紫杉醇	18(35.29)	23(31.08)
既往胸部放疗史	5(9.80)	7(9.46)	0.004	0.949
既往根治性手术史	7(13.73)	13(17.57)	0.332	0.565
肝转移	12(23.53)	10(13.51)	2.088	0.148
PD-L1 TPS			0.270	0.603
TPS<1%	32(62.75)	43(58.11)
TPS≥1%	19(37.25)	31(41.89)

临床资料	观察组(n＝51)	对照组(n＝74)	t/χ²值	P值
吸烟史	32(62.75)	52(70.27)	0.776	0.379
临床分期			8.677	0.003
Ⅲ期	5(9.80)	24(32.43)
Ⅳ期	46(90.20)	50(67.57)
ICIs类型			0.332	0.565
PD-1抑制剂	44(86.27)	61(82.43)
PD-L1抑制剂	7(13.73)	13(17.57)
化疗方案			0.243	0.622
培美曲塞	33(64.71)	51(68.92)
白蛋白紫杉醇	18(35.29)	23(31.08)
既往胸部放疗史	5(9.80)	7(9.46)	0.004	0.949
既往根治性手术史	7(13.73)	13(17.57)	0.332	0.565
肝转移	12(23.53)	10(13.51)	2.088	0.148
PD-L1 TPS			0.270	0.603
TPS<1%	32(62.75)	43(58.11)
TPS≥1%	19(37.25)	31(41.89)

临床资料及影响因素		PR(n)	SD(n)	PD(n)	合计[n(%)]	ORR(%)	χ²值	P值	DCR(%)	χ²值	P值
临床特征
	病理类型						0.629	0.730		0.011	0.994
	腺癌	20	27	13	60(48.00)	33.33			78.33
	鳞癌	13	19	9	41(32.80)	31.71			78.05
	其他	8	11	5	24(19.20)	33.33			79.17
	临床分期						1.261	0.262		2.825	0.093
	Ⅲ期	12	14	3	29(23.20)	41.38			89.66
	Ⅳ期	29	43	24	96(76.80)	30.21			75.00
	既往根治性手术史						0.085	0.771		0.036	0.850
	有	6	10	4	20(16.00)	30.00			80.00
	无	35	47	23	105(84.00)	33.33			78.10
	肝转移						1.229	0.268		5.878	0.015
	有	5	8	9	22(17.60)	22.73			59.09
	无	36	49	18	103(82.40)	34.95			82.52
	PD-L1 TPS						1.960	0.162		1.816	0.178
	<1%	21	35	19	75(60.00)	28.00			74.67
	≥1%	20	22	8	50(40.00)	40.00			84.00
外周血指标	NLR						2.088	0.148		12.468	0.001
	>3.25	13	19	19	51(40.80)	25.49			62.75
	≤3.25	28	38	8	74(59.20)	37.84			89.19
	血红蛋白(g/L)						0.513	0.474		0.787	0.375
	<115	12	19	11	42(33.60)	28.57			73.81
	≥115	29	38	16	83(66.40)	34.94			80.72
	C反应蛋白(mg/L)						1.155	0.282		1.384	0.240
	>8.50	13	22	13	48(38.40)	27.08			72.92
	≤8.50	28	35	14	77(61.60)	36.36			81.82
	碱性磷酸酶(U/L)						0.368	0.544		0.140	0.708
	>95	11	18	9	38(30.40)	28.95			76.32
	≤95	30	39	18	87(69.60)	34.48			79.31
	LDH(U/L)						2.227	0.136		10.867	0.001
	>225	11	17	17	45(36.00)	24.44			62.22
	≤225	30	40	10	80(64.00)	37.50			87.50
	ALB(g/L)						0.394	0.530		6.935	0.008
	<36.52	10	12	13	35(28.00)	28.57			62.86
	≥36.52	31	45	14	90(72.00)	34.44			84.44
	PLR						1.624	0.203		2.451	0.118
	>185.50	10	18	12	40(32.00)	25.00			70.00
	≤185.50	31	39	15	85(68.00)	36.47			82.35
	LMR						0.941	0.332		1.290	0.256
	<2.65	12	20	12	44(35.20)	27.27			72.73
	≥2.65	29	37	15	81(64.80)	35.80			81.48

临床资料及影响因素		PR(n)	SD(n)	PD(n)	合计[n(%)]	ORR(%)	χ²值	P值	DCR(%)	χ²值	P值
临床特征
	病理类型						0.629	0.730		0.011	0.994
	腺癌	20	27	13	60(48.00)	33.33			78.33
	鳞癌	13	19	9	41(32.80)	31.71			78.05
	其他	8	11	5	24(19.20)	33.33			79.17
	临床分期						1.261	0.262		2.825	0.093
	Ⅲ期	12	14	3	29(23.20)	41.38			89.66
	Ⅳ期	29	43	24	96(76.80)	30.21			75.00
	既往根治性手术史						0.085	0.771		0.036	0.850
	有	6	10	4	20(16.00)	30.00			80.00
	无	35	47	23	105(84.00)	33.33			78.10
	肝转移						1.229	0.268		5.878	0.015
	有	5	8	9	22(17.60)	22.73			59.09
	无	36	49	18	103(82.40)	34.95			82.52
	PD-L1 TPS						1.960	0.162		1.816	0.178
	<1%	21	35	19	75(60.00)	28.00			74.67
	≥1%	20	22	8	50(40.00)	40.00			84.00
外周血指标	NLR						2.088	0.148		12.468	0.001
	>3.25	13	19	19	51(40.80)	25.49			62.75
	≤3.25	28	38	8	74(59.20)	37.84			89.19
	血红蛋白(g/L)						0.513	0.474		0.787	0.375
	<115	12	19	11	42(33.60)	28.57			73.81
	≥115	29	38	16	83(66.40)	34.94			80.72
	C反应蛋白(mg/L)						1.155	0.282		1.384	0.240
	>8.50	13	22	13	48(38.40)	27.08			72.92
	≤8.50	28	35	14	77(61.60)	36.36			81.82
	碱性磷酸酶(U/L)						0.368	0.544		0.140	0.708
	>95	11	18	9	38(30.40)	28.95			76.32
	≤95	30	39	18	87(69.60)	34.48			79.31
	LDH(U/L)						2.227	0.136		10.867	0.001
	>225	11	17	17	45(36.00)	24.44			62.22
	≤225	30	40	10	80(64.00)	37.50			87.50
	ALB(g/L)						0.394	0.530		6.935	0.008
	<36.52	10	12	13	35(28.00)	28.57			62.86
	≥36.52	31	45	14	90(72.00)	34.44			84.44
	PLR						1.624	0.203		2.451	0.118
	>185.50	10	18	12	40(32.00)	25.00			70.00
	≤185.50	31	39	15	85(68.00)	36.47			82.35
	LMR						0.941	0.332		1.290	0.256
	<2.65	12	20	12	44(35.20)	27.27			72.73
	≥2.65	29	37	15	81(64.80)	35.80			81.48

影响因素	单变量分析		多变量分析
影响因素	HR(95%CI)	P值	HR(95%CI)	P值
临床分期Ⅳ期	1.627(1.145~2.310)	0.007	1.253(0.821~1.914)	0.298
既往胸部放疗史	0.882(0.611~1.272)	0.495
既往根治性手术史	0.820(0.550~1.276)	0.331
肝转移	1.655(1.121~2.449)	0.012	1.524(1.032~2.248)	0.034
PD-L1 TPS<1%	1.540(1.090~2.178)	0.014	1.311(0.892~1.927)	0.173
NLR>3.25	2.216(1.523~3.212)	0.000	1.854(1.247~2.766)	0.003
血红蛋白<115 g/L	1.326(0.832~1.981)	0.183
C但应蛋白>8.50 mg/L	1.682(1.151~2.454)	0.007	1.322(0.918~1.905)	0.133
碱性磷酸酶>95 U/L	1.253(0.855~1.846)	0.256
LDH>225 U/L	1.981(1.367~2.881)	0.000	1.654(1.114~2.452)	0.013
ALB<36.52 g/L	1.581(1.083~2.315)	0.018	1.416(1.005~1.996)	0.046
PLR>185.50	1.385(0.927~2.078)	0.122
LMR<2.65	1.422(0.951~2.125)	0.085

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