血小板和白蛋白/纤维蛋白原比值在晚期非小细胞肺癌贝伐珠单抗二线治疗的临床意义

doi:10.3877/cma.j.issn.1674-6902.2024.01.007

目的

分析血小板(platelet, PLT)、纤维蛋白原(fibrinogen, FIB)和白蛋白/纤维蛋白原(albumin/fibrinogen, ALB/FIB)对接受贝伐珠单抗二线治疗的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者预后的影响。

方法

回顾性分析我院收治的91例接受贝伐珠单抗二线治疗的晚期NSCLC患者临床和血液参数。PLT、FIB和ALB/FIB根据贝伐珠单抗治疗前的血液检查结果，确定最佳截断值。采用Kaplan-Meier分析和COX回归分析与无进展生存期(progression-free survival, PFS)相关的因素。

结果

单因素分析显示基线PLT、FIB和ALB/FIB与PFS显著相关。多因素分析显示基线PLT和FIB不是PFS的预后因素，年龄(HR：1.719，95%CI：1.036～2.851，P＝0.036)、脑转移(HR：0.475，95%CI：0.269～0.840，P＝0.01)和既往手术(HR：0.479，95%CI：0.251～0.913，P＝0.025)是PFS的预后因素。多因素分析显示，治疗前高水平的ALB/FIB比值是较长PFS的预测因子(HR：0.118，95%CI：0.025～0.553，P＝0.007)。用X-tile软件确定基线PLT、FIB和ALB/FIB的最佳截断值分别为282、4.61和8.8。Kaplan-Meier分析显示：基线低PLT组患者PFS较基线高PLT组预后好(217 d vs. 386 d，P<0.001)，基线低FIB组患者PFS较基线高FIB组预后好(200 d vs. 337 d，P<0.001)，基线高ALB/FIB组患者PFS较基线低ALB/FIB组预后好(360 d vs. 183 d，P<0.001)。

结论

低水平的基线PLT、FIB和高水平的基线ALB/FIB提示在晚期NSCLC患者贝伐珠单抗二线治疗预后较好。

关键词: 晚期非小细胞肺癌, 贝伐珠单抗, 血小板, 白蛋白/纤维蛋白原比值, 预后因素

Objective

To study the effects of platelet (PLT), fibrinogen (FIB) and albumin / fibrinogen (ALB/FIB) on the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received second-line therapy with bevacizumab.

Methods

The baseline clinical characteristics and blood parameters of 91 patients with advanced NSCLC treated with bevacizumab in Qingdao Municipal Hospital were retrospectively analyzed. PLT, FIB and ALB/FIB are based on the latest blood test results before bevacizumab treatment to determine their best cut-off values. Kaplan-Meier analysis and COX regression analysis were used to analyze the factors related to progression-free survival (PFS).

Results

Univariate analysis indicates a significant correlation between baseline PLT, FIB, ALB/FIB, and progression-free survival (PFS). Multivariate analysis reveals that baseline PLT and FIB are not independent prognostic factors for PFS. Instead, age (HR: 1.719, 95%CI: 1.036-2.851, P=0.036), brain metastasis (HR: 0.475, 95%CI: 0.269-0.840, P=0.01), and prior surgery (HR: 0.479, 95%CI: 0.251-0.913, P=0.025) emerge as independent prognostic factors for PFS. Additionally, the analysis indicates that a high pre-treatment level of ALB/FIB ratio independently predicts longer PFS (HR: 0.118, 95%CI: 0.025-0.553, P=0.007). Utilizing X-tile software, the optimal cutoff values for baseline PLT, FIB, and ALB/FIB are determined to be 282, 4.61, and 8.8, respectively. Kaplan-Meier analysis reveals that patients in the baseline low platelet (PLT) group exhibit a more favorable prognosis compared to those in the baseline high PLT group (217 d vs. 386 d, P<0.001). Similarly, patients in the baseline low fibrinogen (FIB) group demonstrate a superior prognosis compared to the baseline high FIB group (200 d vs. 337 d, P<0.001). Furthermore, patients in the baseline high albumin/fibrinogen (ALB/FIB) group exhibit a more favorable prognosis compared to the baseline low ALB/FIB group (360 d vs. 183 d, P<0.001).

Conclusion

Low levels of baseline PLT, FIB and high levels of baseline ALB/FIB may indicate a better prognosis in patients with advanced non-small cell lung cancer treated with bevacizumab.

Key words: Non-small cell lung cancer, Bevacizumab, Platelet, Albumin/fibrinogen ratio, Prognostic factors

图1 91例晚期NSCLC患者无进展生存(PFS)的Kaplan-Meier分析。注：PLT：血小板；FIB：纤维蛋白原；ALB/FIB：白蛋白/纤维蛋白原比值

表1 晚期NSCLC患者PFS的单因素分析

临床资料	变　量	例数	风险比(95%可信区间)	P值
性别	男	55	1.253(0.819～1.918)	0.299
	女	36
年龄(岁)	<65	53	1.166(0.906～2.390)	0.481
	≥65	38
吸烟史	是	31	1.001(0.644～1.555)	0.998
	否	60
脑转移	是	26	0.543(0.315～0.937)	0.028^a
	否	65
胸膜转移	是	38	0.542(0.336～0.875)	0.012^a
	否	65
二线治疗方案	联合化疗	46	1.432(0.937～2.188)	0.097
	联合EGFR抑制剂	28	0.844(0.557～1.278)	0.422
	联合化疗和免疫	17	0.853(0.548～1.342)	0.501
既往手术	是	25	0.571(1.083～3.170)	0.024^a
	否	66
既往局部放疗	是	41	0.789(0.351～0.930)	0.270
	否	50
PLT	<282	66	2.552(1.557～4.184)	0.000^a
	≥282	25
FIB	<4.61	66	2.626(1.606～4.294)	0.000^a
	≥4.61	25
ALB/FIB(AFR)	<8.84	25	0.331(0.204～0.537)	0.000^a
	≥8.84	66

表1 晚期NSCLC患者PFS的单因素分析

临床资料	变　量	例数	风险比(95%可信区间)	P值
性别	男	55	1.253(0.819～1.918)	0.299
	女	36
年龄(岁)	<65	53	1.166(0.906～2.390)	0.481
	≥65	38
吸烟史	是	31	1.001(0.644～1.555)	0.998
	否	60
脑转移	是	26	0.543(0.315～0.937)	0.028^a
	否	65
胸膜转移	是	38	0.542(0.336～0.875)	0.012^a
	否	65
二线治疗方案	联合化疗	46	1.432(0.937～2.188)	0.097
	联合EGFR抑制剂	28	0.844(0.557～1.278)	0.422
	联合化疗和免疫	17	0.853(0.548～1.342)	0.501
既往手术	是	25	0.571(1.083～3.170)	0.024^a
	否	66
既往局部放疗	是	41	0.789(0.351～0.930)	0.270
	否	50
PLT	<282	66	2.552(1.557～4.184)	0.000^a
	≥282	25
FIB	<4.61	66	2.626(1.606～4.294)	0.000^a
	≥4.61	25
ALB/FIB(AFR)	<8.84	25	0.331(0.204～0.537)	0.000^a
	≥8.84	66

表2 晚期NSCLC患者的PFS多因素分析

变　量	风险比(95%可信区间)	P值
性别	1.171(0.649～2.115)	0.599
年龄	1.719(1.036～2.851)	0.036^a
吸烟史	0.714(0.404～1.263)	0.247
脑转移	0.475(0.269～0.840)	0.010^a
胸膜转移	1.165(0.675～2.012)	0.582
手术	0.479(0.251～0.913)	0.025^a
PLT	1.749(0.925～3.307)	0.085
FIB	0.298(0.059～1.500)	0.142
ALB/FIB	0.118(0.025～0.553)	0.007^a

表2 晚期NSCLC患者的PFS多因素分析

变　量	风险比(95%可信区间)	P值
性别	1.171(0.649～2.115)	0.599
年龄	1.719(1.036～2.851)	0.036^a
吸烟史	0.714(0.404～1.263)	0.247
脑转移	0.475(0.269～0.840)	0.010^a
胸膜转移	1.165(0.675～2.012)	0.582
手术	0.479(0.251～0.913)	0.025^a
PLT	1.749(0.925～3.307)	0.085
FIB	0.298(0.059～1.500)	0.142
ALB/FIB	0.118(0.025～0.553)	0.007^a

图2 X-tile软件确定的预处理血液参数的截断值。注：PLT：血小板；FIB：纤维蛋白原；ALB/FIB：白蛋白/纤维蛋白原比值。*P<0.05

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Prognostic significance of platelet and albumin/fibrinogen ratio in second-line therapy of bevacizumab for advanced non-small cell lung cancer

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Prognostic significance of platelet and albumin/fibrinogen ratio in second-line therapy of bevacizumab for advanced non-small cell lung cancer