局部晚期头颈部鳞癌患者血清肿瘤标志物水平对尼妥珠单抗近期疗效及预后的预测价值

Predictive Value of Serum Tumor Marker Levels in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma on the Short-term Efficacy and Prognosis of Nimotuzumab

关键词:  局部晚期头颈部鳞癌  血清肿瘤标志物  尼妥珠单抗  疗效  预后

Key words:  locally advanced head and neck squamous cell carcinoma  serum tumor markers  nimotuzumab  efficacy  prognosis

摘要:

目的 探讨血清肿瘤标志物水平变化对局部晚期头颈部鳞癌患者尼妥珠单抗近期疗效及预后的预测价值。方法 回顾性分析160例接受尼妥珠单抗治疗的局部晚期头颈部鳞癌患者的临床资料，包括治疗后4周的RECIST 1.1疗效评价、无疾病进展生存期（progression-free survival，PFS）以及治疗前和疗效评价时的胸苷激酶1（thymidine kinase 1，TK1）、细胞角蛋白19片段（cytokeratin-19-fragment antigen 21-1，CYFRA21-1）和人鳞状细胞癌相关抗原（squamous-cell carcinoma-related antigen，SCC-Ag）水平。结果 160例局部晚期头颈部鳞癌患者治疗有效率[完全缓解（complete response，CR）+部分缓解（partial response，PR）]为33.13%（53/160），靶向治疗前CR+PR患者血清TK1、CYFRA21-1高于疾病稳定（stable disease，SD）、疾病进展（progressive disease，PD）患者（P<0.05），SCC-Ag基线水平低于SD、PD患者；靶向治疗后CR+PR患者TK1、CYFRA21-1水平降低，PD患者TK1、CYFRA21-1水平升高，SD患者TK1水平降低（P<0.05）。受试者工作特征（receiver operating characteristic，ROC）曲线显示TK1、CYFRA21-1、SCC-Ag变化率与影像学评效一致性的最佳截断点分别为0.265，0.357，0.393，曲线下面积分别为0.774，0.683，0.660。Kaplan-Meier生存分析显示TK1较治疗前升高≤26.5%的患者PFS长于升高>26.5%的患者[22.524个月vs 18.793个月，P=0.002]，CYFRA21-1较治疗前升高≤35.7%的患者中位PFS长于升高>35.7%的患者[22.381个月vs 20.130个月，P=0.030]，SCC-Ag较治疗前升高≤39.3%与升高>39.3%的患者中位PFS比较无显著差异[20.773个月vs 18.947个月，P=0.078]。结论 TK1、CYFRA21-1、SCC-Ag水平对局部晚期头颈部鳞癌患者尼妥珠单抗治疗的近期疗效和预后有重要的预测价值。

Abstract:

OBJECTIVE To explore the predictive value of serum tumor marker levels in patients with locally advanced head and neck squamous cell carcinoma in the treatment effect and prognosis of nimotuzumab. METHODS The clinical data of 160 patients with locally advanced head and neck squamous cell carcinoma who received nimotuzumab, including RECIST 1.1 efficacy evaluation four weeks after treatment, progression-free survival(PFS), and thymidine kinase 1(TK1), cytokeratin-19-fragment (CYFRA21-1) and squamous-cell carcinoma-related antigen(SCC-Ag) levels before and during treatment were evaluated. RESULTS The treatment response rate[complete response(CR) + partial response(PR)] of 160 patients with locally advanced head and neck squamous cell carcinoma was 33.13%(53/160). The baseline levels of serum TK1 and CYFRA21-1 in CR+PR patients were higher than those in patients with SD and PD(P<0.05), and the baseline level of SCC-Ag was lower than that in SD and PD patients. After targeted therapy, the levels of TK1 and CYFRA21-1 in CR+PR patients were decreased, the level of TK1 and CYFRA21-1 in patients with PD were increased, and the level of TK1 in patients with SD was decreased(P<0.05). The ROC curves showed that the best cut-off points for TK1, CYFRA21-1, SCC-Ag change rates and imaging evaluation consistency were 0.265, 0.357, 0.393, and the AUC were 0.774, 0.683, and 0.660, respectively. Kaplan-Meier survival analysis showed that the median PFS was longer in patients with an increase of TK1 ≤ 26.5% than before treatment and in patients with an increase of >26.5%[22.524 months vs 18.793 months, P=0.002]. The median PFS of patients with an elevation of ≤ 35.7% compared with before treatment was longer than that of patients with an elevation of >35.7%[22.381 months vs 20.130 months, P=0.030], there was no significant difference in median PFS between SCC-Ag elevation ≤ 39.3% and elevation >39.3% compared with before treatment[20.773 months vs 18.947 months, P=0.078]. CONCLUSION The levels of TK1, CYFRA21-1, and SCC-Ag have important predictive value for the short-term efficacy and prognosis of nitolimumab in patients with locally advanced head and neck squamous cell carcinoma.