Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy

Abstract

Abstract:

ObjectiveTo investigate the correlation between pre- and post-treatment changing trends in peripheral blood inflammatory markers and efficacy and their predictive value for prognosis in non-small cell lung cancer （NSCLC） patients treated with the first-line immunotherapy plus chemotherapy.MethodsThe clinical data of NSCLC patients admitted to the Department of Radiation and Chemotherapy for Lung Oncology， Zhongnan Hospital of Wuhan University from October 2018 to May 2023 were retrospectively analyzed. Theχ²test was used to analyze the correlation between the changing trend of peripheral blood inflammatory markers and the efficacy of immunotherapy plus chemotherapy. The influencing factors of objective response rate （ORR） were assessed using binary logistic regression analysis. Kaplan-Meier survival curve and Cox proportional hazards model were used to analyze the prognostic value of the changing trend of peripheral blood inflammation markers on patients' prognosis.ResultsA total of 102 NSCLC patients treated with first-line immunotherapy plus chemotherapy were included. The proportion of patients with bone metastases was higher in the lymphocyte to monocyte ratio （LMR） decreased group （n=50） than that in the increased group （n=52）（χ²=4.28，P=0.039）， whereas the pathological type of patients in the platelet to lymphocyte ratio （PLR） decreased group （n=51） was more common in squamous carcinoma compared to patients in the increased group （n=51）（χ²=18.99，P<0.001）， and a higher proportion of patients in the prognostic nutritional index （PNI） decreased group （n=46） was female than that in the increased group （n=56）（χ²=4.29，P=0.038）， with statistically significant differences. The 2-cycle objective response rate （ORR） of patients in the LMR increased and decreased groups was 63.5% （33/52） and 44.0% （22/50）（χ²=3.89，P=0.049）， the 2-cycle ORR of patients in the neutrophil to lymphocyte ratio （NLR） increased （n=24） and decreased （n=78） groups was 29.2% （7/24） and 61.5% （48/78）（χ²=7.74，P=0.005）， and the 2-cycle ORR for patients in the systemic immune inflammatory index （SII） increased group （n=27） and decreased group （n=75） was 33.3% （9/27） and 61.3% （46/75）（χ²=6.26，P=0.012）， with statistically significant differences. Multivariate analysis showed that the changing trend of inflammatory markers in peripheral blood were not related to ORR. The Kaplan-Meier survival curve indicated that patients in the group with SII decreased had longer median progression-free survival （PFS）（not reachedvs.7.1 months，χ²=9.35，P=0.002） and median overall survival （OS）（not reachedvs.16.6 months，χ²=11.08，P<0.001） than those in the SII increased group， and patients in the NLR decreased group had longer median OS （not reachedvs.22.2 months，χ²=4.56，P=0.033） than that in the NLR increased group. Univariate analysis suggested that both brain and bone metastasis （HR=4.04， 95%CI： 1.23-13.35，P=0.022）， increased SII （HR=2.83， 95%CI： 1.41-5.66，P=0.003） were found to be significant factors affecting the PFS of NSCLC patients， both brain and bone metastasis （HR=3.47， 95%CI： 1.05-11.45，P=0.041）， increased NLR （HR=2.17， 95%CI： 1.05-4.51，P=0.037） and increased SII （HR=3.12， 95%CI： 1.54-6.30，P=0.002） were found to be significant factors affecting the OS of NSCLC patients. Multivariate analysis demonstrated that both brain and bone metastasis （HR=4.32， 95%CI： 1.30-14.40，P=0.017） and increased SII （HR=2.89， 95%CI： 1.44-5.81，P=0.003） were independent risk factors for PFS in NSCLC patients， both brain and bone metastasis （HR=3.76， 95%CI： 1.13-12.50，P=0.031） and increased SII （HR=3.47， 95%CI： 1.28-9.41，P=0.014） remained independent risk factors for OS in patients with NSCLC.ConclusionThe changing trend of peripheral blood inflammatory markers of NSCLC patients cannot independently predict the efficacy of 2-cycle immunotherapy plus chemotherapy. Both brain and bone metastasis， as well as the changing trend of SII can be used as important indicators to predict PFS and OS in advanced NSCLC patients treated with first-line immunotherapy plus chemotherapy. The simultaneous occurrence of brain and bone metastasis and SII increased suggest poor prognosis of NSCLC patients.

Key words:Carcinoma,non-small-cell lung,Immunotherapy,Prognosis,Inflammatory markers,Survival analysis

Fan Zhipeng, Yu Jing, Hu Jing, Liao Zhengkai, Xu Yu, Ouyang Wen, Xie Conghua. Predictive value of changes in inflammatory markers for prognosis in patients with advanced non-small cell lung cancer treated with the first-line immunotherapy plus chemotherapy[J]. Journal of International Oncology, 2024, 51(5): 257-266.

Figures/Tables6

基线特征	例数	MPV				LMR				NLR
基线特征	例数	上升组（n=25）	下降组（n=77）	χ²值	P值	上升组（n=52）	下降组（n=50）	χ²值	P值	上升组（n=24）	下降组（n=78）	χ²值	P值
年龄（岁）
<65	54	15	39	0.66	0.416	27	27	0.04	0.834	11	43	0.64	0.425
≥65	48	10	38	0.66	0.416	25	23	0.04	0.834	13	35	0.64	0.425
性别
男	86	19	67	1.00	0.318	45	41	0.40	0.529	21	65	0.03	0.865
女	16	6	10	1.00	0.318	7	9	0.40	0.529	3	13	0.03	0.865
病理类型
鳞状细胞癌	52	15	37	1.08	0.299	28	24	0.35	0.555	12	40	0.01	0.913
非鳞状细胞癌	50	10	40	1.08	0.299	24	26	0.35	0.555	12	38	0.01	0.913
TNM分期
ⅢB~ⅢC	27	8	19	0.52	0.471	15	12	0.31	0.579	8	19	0.76	0.384
Ⅳ	75	17	58	0.52	0.471	37	38	0.31	0.579	16	59	0.76	0.384
脑转移
是	11	3	8	<0.01	>0.999	6	5	0.06	0.802	1	10	0.67	0.413
否	91	22	69	<0.01	>0.999	46	45	0.06	0.802	23	68	0.67	0.413
骨转移
是	31	8	23	0.04	0.841	11	20	4.28	0.039	11	20	3.54	0.060
否	71	17	54	0.04	0.841	41	30	4.28	0.039	13	58	3.54	0.060
同时脑、骨转移
是	4	0	4	-	0.570	1	3	0.30	0.582	1	3	-	>0.999
否	98	25	73	-	0.570	51	47	0.30	0.582	23	75	-	>0.999
基线特征	例数	PLR				SII				PNI
基线特征	例数	上升组（n=51）	下降组（n=51）	χ²值	P值	上升组（n=27）	下降组（n=75）	χ²值	P值	上升组（n=56）	下降组（n=46）	χ²值	P值
年龄（岁）
<65	54	29	25	0.63	0.427	13	41	0.34	0.561	28	26	0.43	0.511
≥65	48	22	26	0.63	0.427	14	34	0.34	0.561	28	20	0.43	0.511
性别
男	86	42	44	0.30	0.586	23	63	<0.01	>0.999	51	35	4.29	0.038
女	16	9	7	0.30	0.586	4	12	<0.01	>0.999	5	11	4.29	0.038
病理类型
鳞状细胞癌	52	15	37	18.99	<0.001	11	41	1.54	0.215	31	21	0.95	0.329
非鳞状细胞癌	50	36	14	18.99	<0.001	16	34	1.54	0.215	25	25	0.95	0.329
TNM分期
ⅢB~ⅢC	27	12	15	0.45	0.501	9	18	0.89	0.346	17	10	0.96	0.326
Ⅳ	75	39	36	0.45	0.501	18	57	0.89	0.346	39	36	0.96	0.326
脑转移
是	11	6	5	0.10	0.750	2	9	0.09	0.766	6	5	<0.01	>0.999
否	91	45	46	0.10	0.750	25	66	0.09	0.766	50	41	<0.01	>0.999
骨转移
是	31	17	14	0.42	0.518	9	22	0.15	0.698	16	15	0.20	0.659
否	71	34	37	0.42	0.518	18	53	0.15	0.698	40	31	0.20	0.659
同时脑、骨转移
是	4	2	2	<0.01	>0.999	1	3	<0.01	>0.999	3	1	0.10	0.755
否	98	49	49	<0.01	>0.999	26	72	<0.01	>0.999	53	45	0.10	0.755

因素	单因素分析			多因素分析
因素	OR值	95%CI	P值	OR值	95%CI	P值
年龄（< 65岁/ ≥ 65岁）	0.98	0.45~2.14	0.963	-	-	-
性别（男/女）	0.66	0.22~1.97	0.455	-	-	-
病理类型（鳞状细胞癌/非鳞状细胞癌）	2.21	1.00~4.89	0.050	-	-	-
TNM分期（Ⅳ/ⅢB~ⅢC）	1.12	0.46~2.70	0.801	-	-	-
脑转移（有/无）	1.03	0.29~3.61	0.965	-	-	-
骨转移（有/无）	0.60	0.26~1.41	0.243	-	-	-
同时脑、骨转移（有/无）	0.27	0.03~2.70	0.266	-	-	-
MPV变化（上升/下降）	1.12	0.45~2.77	0.810	-	-	-
LMR变化（上升/下降）	2.21	1.00~4.89	0.050	-	-	-
NLR变化（上升/下降）	0.26	0.10~0.69	0.007	0.37	0.10~1.43	0.149
PLR变化（上升/下降）	0.49	0.22~1.08	0.075	-	-	-
SII变化（上升/下降）	0.32	0.13~0.80	0.014	0.61	0.17~2.18	0.445
PNI变化（上升/下降）	1.57	0.77~3.44	0.264	-	-	-

因素	单因素分析			多因素分析
因素	HR值	95%CI	P值	HR值	95%CI	P值
年龄（< 65岁/ ≥ 65岁）	1.58	0.78~3.19	0.203	-	-	-
性别（男/女）	1.14	0.40~3.25	0.804	-	-	-
病理类型（鳞状细胞癌/非鳞状细胞癌）	1.46	0.73~2.92	0.282	-	-	-
TNM分期（Ⅳ/ⅢB~ⅢC）	0.87	0.42~1.84	0.719	-	-	-
放疗（有/无）	2.00	0.93~4.30	0.078	-	-	-
脑转移（有/无）	1.35	0.47~3.83	0.578	-	-	-
骨转移（有/无）	1.25	0.61~2.58	0.549	-	-	-
同时脑、骨转移（有/无）	4.04	1.23~13.35	0.022	4.32	1.30~14.40	0.017
MPV变化（上升/下降）	1.03	0.46~2.28	0.947	-	-	-
LMR变化（上升/下降）	0.61	0.30~1.21	0.157	-	-	-
NLR变化（上升/下降）	2.02	0.98~4.18	0.057	-	-	-
PLR变化（上升/下降）	1.51	0.76~3.01	0.245	-	-	-
SII变化（上升/下降）	2.83	1.41~5.66	0.003	2.89	1.44~5.81	0.003
PNI变化（上升/下降）	0.60	0.30~1.18	0.139	-	-	-

因素	单因素分析			多因素分析
因素	HR值	95%CI	P值	HR值	95%CI	P值
年龄（< 65岁/ ≥ 65岁）	1.44	0.71~2.90	0.308	-	-	-
性别（男/女）	1.16	0.41~3.31	0.776	-	-	-
病理类型（鳞状细胞癌/非鳞状细胞癌）	1.40	0.70~2.79	0.344	-	-	-
TNM分期（Ⅳ/ⅢB~ⅢC）	0.92	0.44~1.93	0.816	-	-	-
放疗（有/无）	1.42	0.66~3.07	0.372	-	-	-
脑转移（有/无）	1.14	0.40~3.24	0.808	-	-	-
骨转移（有/无）	1.15	0.56~2.37	0.708	-	-	-
同时脑、骨转移（有/无）	3.47	1.05~11.45	0.041	3.76	1.13~12.50	0.031
MPV变化（上升/下降）	1.03	0.46~2.28	0.952	-	-	-
LMR变化（上升/下降）	0.58	0.29~1.16	0.126	-	-	-
NLR变化（上升/下降）	2.17	1.05~4.51	0.037	0.89	0.32~2.49	0.816
PLR变化（上升/下降）	1.78	0.88~3.56	0.106	-	-	-
SII变化（上升/下降）	3.12	1.54~6.30	0.002	3.47	1.28~9.41	0.014
PNI变化（上升/下降）	0.58	0.29~1.16	0.123	-	-	-

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