甲胎蛋白联合谷氨酰转移酶对晚期乙肝相关性肝癌男性患者应用仑伐替尼治疗后进展的预测价值

赵磊; 王文鑫; 毕京峰; 孟芳霖; 谢小慧; 石磊; 徐哲; 王福生

doi:10.3969/j.issn.2095-5227.2022.05.003

甲胎蛋白联合谷氨酰转移酶对晚期乙肝相关性肝癌男性患者应用仑伐替尼治疗后进展的预测价值

Alpha fetoprotein combined gamma-glutamyl transferase in predicting cancer progression in male patients with advanced hepatitis B virus-related hepatocellular carcinoma treated by lenvatinib

摘要

摘要:
背景甲胎蛋白(alpha fetoprotein，AFP)是公认的肝癌的肿瘤标志物，在肝癌早筛中发挥重要作用，但通过单独监测AFP水平对肝癌预后评估的作用仍十分有限。近年来，谷氨酰转移酶(gamma-glutamyl transferase，GGT)被发现在肝癌的诊断和预后评估中具有应用价值。然而，二者联合预测肝癌进展的临床意义尚不清楚。
目的探讨甲胎蛋白联合谷氨酰转移酶对晚期乙肝相关性肝癌男性患者应用仑伐替尼治疗后进展的预测评估作用。
方法回顾分析解放军总医院第五医学中心2018年6月- 2021年6月收治的85例乙肝相关性肝癌男性成年患者的临床资料。所有患者均应用仑伐替尼为一线抗肿瘤药物，以RECIST1.1为标准，每4 ~ 8周进行疗效评价并监测AFP和GGT水平。治疗至6个月时，将肿瘤进展患者纳入进展组(n=22)，将完全缓解、部分缓解和疾病稳定的患者纳入非进展组(n=63)。利用受试者工作特征曲线分析AFP、GGT以及两者联合对仑伐替尼治疗后肿瘤进展的预测作用。
结果两组年龄、既往主要病史、Child-Pugh分级、BCLC分期和PS评分无统计学差异(P＞0.05)，治疗前AFP和GGT水平无统计学差异(P＞0.05)。AFP差值预测治疗后进展的曲线下面积、敏感度、特异性分别为0.771(95% CI：0.647 ~ 0.896)、84.10%、68.20%；GGT差值预测治疗后进展的曲线下面积、敏感度、特异性分别为0.763(95% CI：0.629 ~ 0.898)、98.40%、54.50%；AFP差值联合GGT差值预测治疗后进展的曲线下面积、敏感度、特异性分别为0.849(95% CI：0.744 ~ 0.954)、93.70%、72.70%，二者联合后预测效能优于AFP(P=0.023)。AFP差值的最佳截断点为52 ng/mL，GGT差值的最佳截断点为21.5 U/L。
结论 AFP联合GGT对晚期乙肝相关性肝癌进展有一定预测评估作用。

Abstract:
Background Alpha-fetoprotein (AFP) is of well-recognized as a tumor marker for screening hepatocellular carcinoma (HCC), but with a limited efficacy when used alone. In recent years, gamma-glutamyl transferase (GGT) has been recognized to play a vital role in the early diagnosis and prognosis assessment in patients with HCC. However, the clinical significance of AFP combined with GGT in screening HCC progression is still poorly understood.
Objective To investigate the clinical significance of AFP combined with GGT in predicting progressive disease (PD) treated by lenvatinib in male patients with advanced HBV-related HCC.
Methods A hospital-based retrospective study was conducted in 85 consecutive patients with advanced HBV-related HCC who had been treated with lenvatinib in the Fifth Medical Center of Chinese PLA General Hospital from June 2018 to June 2021. All patients were treated with lenvatinib as the first-line antitumor drug, according to the RECIST 1.1, the curative effectiveness was evaluated every 4-8 weeks, and the levels of AFP and GGT were also monitored. Patients were divided into PD group (n=22) and non-PD group (n=63) according to the evaluation of therapeutic effect of tumor-targeted therapy. The efficacy of AFP and GGT in predicting PD in male patients with advanced HBV-related HCC treated by lenvatinib was analyzed by the Receiver Operating Characteristic Curve (ROC).
Results There was no statistical significance in age, previous history, the score of Child-Pugh, the stage of BCLC, the score of performance status, the AFP level and GGT level between the two groups (all P>0.05). The AUC of ROC, sensitivity and specificity of △AFP in predicting PD in patients with hepatocellular carcinoma were 0.771 (95% CI: 0.647-0.896), 84.10%, 68.20%, respectively, they were 0.763 (95% CI: 0.629-0.898), 98.40%, 54.50% for △GGT, and 0.849 (95% CI: 0.744-0.954), 93.70%, 72.70% for the combined detection. The efficacy of combined detection in predicting PD was higher than that of AFP (P=0.0233). The optimal cut-off value of △AFP difference was 52 ng/mL, and 21.5 U/L for △GGT.
Conclusion The combination of AFP and GGT is valuable in predicting disease progression in patients with HBV-related HCC.

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