Prediction of efficacy of early-stage tumor markers combined with NLR and PLR for immunotherapy in gastric cancer

doi:10.3760/cma.j.cn371439-20231016-00025

Abstract

Abstract:

Objective To explore the predictive value of early serum tumor markers （STM）， neutrophil to lymphocyte ratio （NLR）， platelet to lymphocyte ratio （PLR） combination score on the efficacy of gastric cancer immunotherapy. Methods A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1， 2020 to June 30， 2022 were selected. Patients' leading STM， NLR， PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic （ROC） curve. The clinical efficacy and prognosis of different leading STM， NLR， PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival. Results The best truncation value for NLR was 2.75， and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy， the objective response rate （ORR） was 23.7% （18/76）， and the disease control rate （DCR） was 88.2% （67/76）. There were no significant differences in ORR [（20.9% （9/43） vs. 27.3% （9/33）]， DCR [83.7% （36/43） vs. 93.9% （31/33）] between the high NLR group （n=43） and low NLR group （n=33）（χ²=0.42， P=0.519； χ²=1.02， P=0.313）. There were no significant differences in ORR [27.3% （12/44） vs. 18.8% （6/32）]， DCR [81.8% （36/44） vs. 96.9% （31/32）] between the high PLR group （n=44） and low PLR group （n=32）（χ²=0.75， P=0.388； χ²=2.71， P=0.555）. The ORR for the high combined score group （n=39） and low combined score group （n=37） was 17.9% （7/39） and 29.7% （11/37）， respectively， with no statistically significant difference （χ²=1.46， P=0.230）； the DCR was 79.5% （31/39） and 97.3% （36/37）， respectively， with a statistically significant difference （χ²=4.19， P=0.041）. The median progression free survival （PFS） and overall survival （OS） of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months， respectively， with a statistically significant difference （χ²=7.95， P=0.005）； the median OS was 12.0 and 14.0 months， respectively， with no statistically significant difference （χ²=1.04， P=0.307）. The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months， respectively， with a statistically significant difference （χ²=3.90， P=0.048）； the median OS was 13.0 and 13.0 months， respectively， with no significant difference （χ²=0.02， P=0.896）. The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months， respectively， with a statistically significant difference （χ²=13.52， P<0.001）； the median OS was 12.0 and 14.0 months， respectively， with a statistically significant difference （χ²=5.02， P=0.025）. ROC curve analysis showed that the area under curve （AUC） of leading STM， NLR， PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662， 0.697， 0.601 and 0.773. Univariate analysis showed that， surgery （HR=0.59， 95%CI： 0.36-0.95， P=0.031）， leading STM （HR=0.57， 95%CI： 0.34-0.93， P=0.026）， NLR （HR=0.54， 95%CI： 0.34-0.87， P=0.011）， combined score （HR=0.42， 95%CI： 0.26-0.68， P<0.001） were all influencing factors for PFS in gastric cancer patients received immunotherapy； tumor stage （HR=0.30， 95%CI： 0.12-0.75， P=0.011）， leading STM （HR=0.28， 95%CI： 0.15-0.50， P<0.001）， combined score （HR=0.55， 95%CI： 0.31-0.96， P=0.036） were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that， leading STM （HR=0.56， 95%CI： 0.33-0.98， P=0.041） was an independent influencing factor for PFS in gastric cancer patients received immunotherapy； tumor stage （HR=0.29， 95%CI： 0.11-0.76， P=0.012）， leading STM （HR=0.32， 95%CI： 0.17-0.58， P<0.001）， combined score （HR=0.46， 95%CI： 0.25-0.82， P=0.009） were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion The combined score of leading STM， NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer， and can predict the efficacy of immunotherapy for gastric cancer.

Key words: Stomach neoplasms, Biomarkers, tumor, Immune checkpoint inhibitors, Neutrophil to lymphocyte ratio, Platelet to lymphocyte ratio

Xie Shuping, Sun Yahong, Wang Chao. Prediction of efficacy of early-stage tumor markers combined with NLR and PLR for immunotherapy in gastric cancer[J]. Journal of International Oncology, 2024, 51(3): 157-165.

Figures/Tables 12

References 29

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一般临床资料	高联合评分组（n=39）	低联合评分组（n=37）	χ²值	P值
年龄（岁）
≥65	16	16	0.04	0.845
<65	23	21	0.04	0.845
性别
男	28	28	0.15	0.701
女	11	9	0.15	0.701
BMI
<18.5或>23.5	11	15	1.28	0.257
18.5~23.5	28	22	1.28	0.257
肿瘤分期
Ⅲ	8	7	0.03	0.861
Ⅳ	31	30	0.03	0.861
组织学类型
腺癌	36	37	1.28	0.258
鳞状细胞癌	3	0	1.28	0.258
转移部位数量（个）
<2	18	14	0.54	0.463
≥2	21	23	0.54	0.463
肿瘤部位
贲门	15	11	2.53	0.469
胃底	1	4
胃体	16	14
胃窦	7	8
饮酒史
有	15	17	0.44	0.509
无	24	20	0.44	0.509
吸烟史
有	15	16	0.18	0.672
无	24	21	0.18	0.672
治疗类型
单药免疫治疗	4	4	<0.01	>0.999
联合治疗	35	33	<0.01	>0.999
ECOG评分（分）
0	29	32	1.76	0.184
1	10	5	1.76	0.184
放疗
是	7	4	0.78	0.377
否	32	33	0.78	0.377
免疫相关不良反应
有	34	31	0.14	0.708
无	5	6	0.14	0.708

组别	CR	PR	SD	PD	客观缓解	疾病控制
高NLR组（n=43）	0（0）	9（20.9）	27（62.8）	7（16.3）	9（20.9）	36（83.7）
低NLR组（n=33）	0（0）	9（27.3）	22（66.7）	2（6.1）	9（27.3）	31（93.9）
χ²值					0.42	1.02
P值					0.519	0.313

组别	CR	PR	SD	PD	客观缓解	疾病控制
高PLR组（n=44）	0（0）	12（27.3）	24（54.5）	8（18.2）	12（27.3）	36（81.8）
低PLR组（n=32）	0（0）	6（18.8）	25（78.1）	1（3.1）	6（18.8）	31（96.9）
χ²值					0.75	2.71
P值					0.388	0.555

组别	CR	PR	SD	PD	客观缓解	疾病控制
高联合评分组（n=39）	0（0）	7（17.9）	24（61.5）	8（20.5）	7（17.9）	31（79.5）
低联合评分组（n=37）	0（0）	11（29.7）	25（64.9）	1（2.7）	11（29.7）	36（97.3）
χ²值					1.46	4.19
P值					0.230	0.041

因素		PFS			OS
因素	HR值	95%CI	P值	HR值	95%CI	P值
年龄（≥65岁/<65岁）	0.95	0.60~1.51	0.818	1.42	0.80~2.54	0.234
性别（男/女）	1.44	0.84~2.45	0.185	1.42	0.76~2.64	0.276
BMI（<18.5或>23.5/18.5~23.5）	1.07	0.65~1.74	0.794	1.11	0.63~1.97	0.715
肿瘤分期（Ⅲ期/Ⅳ期）	0.64	0.36~1.13	0.123	0.30	0.12~0.75	0.011
组织学类型（腺癌/鳞状细胞癌）	1.13	0.35~3.61	0.843	0.04	0.00~5.44	0.202
转移（有/无）	0.66	0.30~1.46	0.306	3.46	0.84~14.28	0.086
饮酒史（有/无）	1.14	0.71~1.82	0.527	1.47	0.84~2.54	0.176
吸烟史（有/无）	1.35	0.84~2.18	0.219	1.12	0.64~1.98	0.695
治疗类型（单药免疫/联合治疗）	0.61	0.28~1.34	0.218	0.55	0.20~1.53	0.248
手术（是/否）	0.59	0.36~0.95	0.031	0.64	0.36~1.14	0.129
ECOG评分（0分/1分）	1.91	0.65~2.18	0.572	1.43	0.69~2.98	0.342
前导的STM（升高/降低）	0.57	0.34~0.93	0.026	0.28	0.15~0.50	<0.001
NLR（高/低）	0.54	0.34~0.87	0.011	0.76	0.43~1.34	0.335
PLR（高/低）	0.67	0.42~1.08	0.098	1.04	0.59~1.81	0.902
联合评分（高/低）	0.42	0.26~0.68	<0.001	0.55	0.31~0.96	0.036