派安普利单抗联合化疗对晚期非小细胞肺癌患者血管生成及循环内皮细胞的影响

摘要/Abstract

摘要：

目的探讨派安普利单抗联合化疗对晚期非小细胞肺癌（NSCLC）患者血管生成及循环内皮细胞的影响。方法收集2021年8月至2023年1月邢台医学高等专科学校第二附属医院收治的121例晚期NSCLC患者的临床资料，根据治疗方案将患者分成对照组（n=57）和观察组（n=64），对照组患者行常规化疗（顺铂+紫杉醇），观察组患者在常规化疗的基础上加用派安普利单抗治疗。比较两组患者近期临床疗效、生命质量、免疫功能指标、血管生成因子[（内皮抑素、胰岛素样生长因子1（IGF-1）和血管内皮生长因子（VEGF）]、循环内皮细胞及不良反应等参数。结果治疗6个周期后，观察组患者客观缓解率[67.19%（43/64）比49.12%（28/57）]、疾病控制率[（87.50%（56/64）比70.18%（40/57）]均高于对照组，差异均有统计学意义（χ²=4.06，P=0.044；χ²=5.52，P=0.019）。观察组患者生命质量评分[（56.77±6.81）分]明显高于对照组[（47.73±8.23）分]，差异有统计学意义（t=6.61，P<0.001）；观察组患者T细胞亚群CD3⁺水平[（63.59±9.00）%比（53.06±8.80）%，t=6.49，P<0.001]、CD4⁺水平[（46.54±8.20）%比（30.74±7.32）%，t=11.13，P<0.001]和CD4⁺/CD8⁺比值（1.90±0.36比1.21±0.28，t=11.66，P<0.001）明显高于对照组，差异均有统计学意义；观察组患者内皮抑素[（48.99±3.43）μmol/L]明显高于对照组[（31.35±3.87）μmol/L]，差异有统计学意义（t=26.58，P<0.001），IGF-1[（102.31±20.35）μg/L比（134.98±19.02）μg/L]和VEGF[（31.70±4.32）pg/ml比（58.71±5.99）pg/ml]明显低于对照组，差异有统计学意义（t=18.73，P<0.001；t=28.14，P<0.001）。观察组患者循环内皮细胞数[（58.77±10.03）个/ml]明显低于对照组[（87.01±8.01）个/ml]，差异有统计学意义（t=17.20，P<0.001）。治疗期间，两组患者胃肠道反应（χ²=0.01，P=0.908）、白细胞减少（χ²=0.64，P=0.424）、血小板减少（χ²=0.28，P=0.597）、贫血（χ²=1.66，P=0.197）、肾毒性（χ²=0.64，P=0.424）、皮疹（χ²=1.33，P=0.249）不良反应发生率差异均无统计学意义。结论派安普利单抗联合化疗治疗晚期NSCLC效果显著，可提高患者免疫功能，改善生命质量，抑制血管生成，安全可靠。

关键词:癌,非小细胞肺,抗肿瘤联合化疗方案,血管内皮生成因子类,循环内皮细胞,治疗结果

Abstract:

ObjectiveTo explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer （NSCLC）.MethodsThe retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group （n=57）and an observation group （n=64）based on the designated treatment protocol. Specifically，individuals in the control group received standard chemotherapy（cisplatin+paclitaxel），while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy，quality of life，immune function parameters，angiogenic factors [including endostatin，insulin-like growth factor 1 （IGF-1），and vascular endothelial growth factor （VEGF）]，circulating endothelial cells，and adverse reactions within the two groups.ResultsAfter 6 courses of treatment，the objective response rate [67.19% （43/64）vs.49.12% （28/57）] and disease control rate [87.50% （56/64）vs.70.18% （40/57）] in observation group were higher than those in control group，with statistically significant differences （χ²=4.06，P=0.044；χ²=5.52，P=0.019）. The quality of life score of observation group [（56.77±6.81）points] was significantly higher than that of control group [（47.73±8.23）points]，with a statistically significant difference （t=6.61，P<0.001）； The T cell subgroup CD3⁺levels [（63.59±9.00）%vs.（53.06±8.80%），t=6.49，P<0.001]，CD4⁺levels [（46.54±8.20）%vs.（30.74±7.32）%，t=11.13，P<0.001] and CD4⁺/CD8⁺ratio （1.90±0.36vs.1.21±0.28，t=11.66，P<0.001）in observation group were significantly higher than those in control group，with statistically significant differences； Endostatin in observation group [（48.99±3.43）μmol/L] was significantly higher than that in control group [（31.35±3.87）μmol/L]，with a statistically significant difference （t=26.58，P<0.001），IGF-1 [（102.31±20.35）μg/Lvs.（134.98±19.02）μg/L] and VEGF [（31.70±4.32）pg/mlvs.（58.71±5.99）pg/ml] were significantly lower in observation group than those in control group，with statistically significant differences （t=18.73，P<0.001；t=28.14，P<0.001）. The number of circulating endothelial cells in observation group [（58.77±10.03）/ml] was significantly lower than that in control group [（87.01±8.01）/ml]，with a statistically significant difference （t=17.20，P<0.001）. During treatment，there were no statistically significant differences in the incidence of gastrointestinal reaction （χ²=0.01，P=0.908），leukopenia （χ²=0.64，P=0.424），thrombocytopenia （χ²=0.28，P=0.597），anemia （χ²=1.66，P=0.197），nephrotoxicity （χ²=0.64，P=0.424），skin rash （χ²=1.33，P=0.249）between the two groups.ConclusionThe combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality，ameliorate their overall quality of life，suppress angiogenesis，and exhibits a commendable profile of safety and reliability.

Key words:Carcinoma,non-small-cell lung,Antineoplastic combined chemotherapy protocols,Vascular endothelial growth factors,Circulating endothelial cells,Treatment outcome

姜溪, 武永存, 梁艳, 楚丽, 段颖欣, 王力军, 霍俊杰. 派安普利单抗联合化疗对晚期非小细胞肺癌患者血管生成及循环内皮细胞的影响[J]. 国际肿瘤学杂志, 2024, 51(2): 89-94.

Jiang Xi, Wu Yongcun, Liang Yan, Chu Li, Duan Yingxin, Wang Lijun, Huo Junjie. Impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer[J]. Journal of International Oncology, 2024, 51(2): 89-94.

图/表6

表1

两组NSCLC患者基线资料比较（例/ $\bar{x}±s$）"

基线资料	观察组（n=64）	对照组（n=57）	χ²/t值	P值
性别
男	32	23	1.13	0.287
女	32	34	1.13	0.287
年龄（岁）	64.99±3.15	65.22±2.81	0.42	0.674
ECOG评分（分）	1.67±0.41	1.79±0.33	1.76	0.081
病理类型
腺癌	21	10	3.69	0.055
鳞状细胞癌	43	47	3.69	0.055
吸烟史
有	8	5	0.44	0.509
无	56	52	0.44	0.509
饮酒史
有	11	6	1.11	0.293
无	53	51	1.11	0.293

表1

组别	治疗前	治疗6个周期后	t值	P值
观察组（n=64）	40.81±7.32	56.77±6.81	12.42	<0.001
对照组（n=57）	41.12±6.66	47.73±8.23	4.82	<0.001
t值	0.24	6.61
P值	0.809	<0.001

表2

组别	CD3⁺（%）			CD4⁺/CD8⁺
观察组（n=64）	57.11±10.67	63.59±9.00^a	36.12±6.57	46.54±8.20^a	1.37±0.40	1.90±0.36^a
对照组（n=57）	57.49±9.85	53.06±8.80^a	35.49±6.06	30.74±7.32^a	1.36±0.33	1.21±0.28^a
t值	0.20	6.49	0.55	11.13	0.15	11.66
P值	0.840	<0.001	0.586	<0.001	0.882	<0.001

表3

组别	内皮抑素（μmol/L）			VEGF（pg/ml）
观察组（n=64）	15.01±3.04	48.99±3.43^a	154.34±24.51	102.31±20.35^a	75.19±4.48	31.70±4.32^a
对照组（n=57）	15.12±4.02	31.35±3.87^a	150.99±29.87	134.98±19.02^a	74.34±5.71	58.71±5.99^a
t值	0.17	26.58	0.68	18.73	0.92	28.14
P值	0.867	<0.001	0.500	<0.001	0.362	<0.001

表4

组别	治疗前	治疗6个周期后	t值	P值
观察组（n=64）	115.01±15.69	58.77±10.03	44.85	<0.001
对照组（n=57）	119.26±15.20	87.01±8.01	14.34	<0.001
t值	1.51	17.20
P值	0.134	<0.001

表5

组别	胃肠道反应	白细胞减少	血小板减少	贫血	肾毒性	皮疹
观察组（n=64）	6（9.38）	6（9.38）	10（15.63）	7（10.94）	6（9.38）	4（6.25）
对照组（n=57）	5（8.77）	8（14.04）	7（12.28）	11（19.30）	8（14.04）	7（12.28）
χ²值	0.01	0.64	0.28	1.66	0.64	1.33
P值	0.908	0.424	0.597	0.197	0.424	0.249

表6

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