[目的]评估外周血指标对头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)患者接受免疫检查点抑制剂治疗后预后的预测价值.[方法]回顾性收集接受免疫检查点抑制剂治疗的HNSCC患者117例的临床和生存数据.使用X-tile确定基线和治疗2个周期后乳酸脱氢酶(lactate de-hydrogenase,LDH)、纤维蛋白原(fibrinogen,FIB)和衍生中性粒细胞-淋巴细胞比值(derived neutrophil lymphocyte ratio,dNLR)、纤维蛋白原与白蛋白比值(fibrinogen to albumin ratio,FAR)和预后营养指数(prognostic nutritional index,PNI)最佳截断值.使用Kaplan-Meier方法进行生存分析,并利用Cox比例风险回归模型进行单因素和多因素分析.根据多变量分析结果构建预后评分模型的预后列线图.[结果]HNSCC患者接受免疫检查点抑制剂治疗后,疾病控制率为87.2％,客观缓解率为44.4％.对免疫检查点抑制剂有应答患者的基线LDH、FIB和dNLR水平显著性降低(P均＜0.05).生存分析显示,基线LDH＞231 U/L(x2=5.537,P=0.019)、基线 FIB＞4.4 ng/mL(x2=7.409,P=0.006)和基线 FAR＞0.11(x2=5.144,P=0.023)患者具有较短的无进展生存期.接受免疫一线治疗相比较于二线、三线治疗显示出更好的无进展生存期(8.2个月vs7.7个月vs4.5个月,x2=6.195,P=0.045).多因素回归分析显示免疫治疗线数、淋巴结转移及基线LDH水平是影响患者无进展生存期的独立预后因素,纳入构建预后列线图,该模型C指数为0.662.经过 2 个免疫治疗周期后,FIB≤4.47(8.8 个月 vs 6.0 个月,x2=4.216,P=0.040)、dNLR≤ 1.56(9.2 个月 vs 7.2 个月,x2=4.572,P=0.032)和 PNI＞44.1(8.2 个月 vs 5.5 个月,x2=4.068,P=0.044)与较长的 PFS 相关联.[结论]基线LDH、FIB和FAR水平与PFS密切相关.动态变化分析显示,LDH、FIB、FAR和PNI在疾病进展时出现显著性变化.外周血指标可作为接受免疫治疗的HNSCC患者的预后因素,并为个体化治疗提供了依据.
Predicting Value of Peripheral Blood Indicators for Patients with Head and Neck Squamous Cell Carcinoma Undergoing Immunotherapy
[Objective]To evaluate the predictive value of peripheral blood indicators for the prognosis of pa-tients with head and neck squamous cell carcinoma(HNSCC)undergoing immune checkpoint inhibitors(ICIs)therapy.[Methods]Clinical and survival data of 117 patients with HNSCC undergoing ICIs therapy were ret-rospectively analyzed.The optimal cut-off values of lactate dehydrogenase(LDH),fibrinogen(FIB),fibrinogen to albumin ratio(FAR),derived neutrophil lymphocyte ratio(dNLR)and prognostic nutritional index(PNI)at baseline and after 2 cycles of treatment were determined with X-tile software.Kaplan-Meier method was em-ployed for survival analysis,and univariate and multivariate Cox proportional hazards regression model was used to examine the predicting factors of survival.A prognostic nomogram was constructed based on the results of multivariate analysis.[Results]After ICIs therapy,the disease control rate was 87.2％,and the objective response rate was 44.4％.Baseline levels of LDH,FIB,and dNLR were significantly lower in patients re-sponding to ICIs(P all＜0.05).Survival analysis revealed that patients with baseline LDH＞231 U/L(x2=5.537,P=0.019),FIB＞4.4 ng/mL(x2=7.409,P=0.006)and FAR＞0.11(x2=5.144,P=0.023)had shorter progression-free survival(PFS).Patients receiving first-line immunotherapy showed better PFS compared to second-line and beyond(8.2 vs 7.7 vs 4.5 months,x2=6.195,P=0.045).Multivariate regression analysis showed the number of immune therapy lines,lymph node metastasis and baseline LDH were independent prognostic factors for PFS.A prognostic nomogram was constructed with a C-index of 0.662.After two cycles of immune therapy,FIB≤4.47(8.8 vs 6.0 months,x2=4.216,P=0.040),dNLR≤1.56(9.2 vs 7.2 months,x2=4.572,P=0.032)and PNI＞44.1(8.2 vs 5.5 months,x2=4.068,P=0.044)were associated with longer PFS.[Conclusion]Baseline levels of LDH,FIB and FAR are closely associated with PFS of HNSCC patients receiving immunotherapy.Dynamic changes analysis reveals significant alterations in LDH,FIB,FAR and PNI at disease progression.Peripheral blood indicators can be used as prognostic factors for HNSCC patients receiving immunotherapy,which provides the basis for individualized treatment.
head and neck squamous cell carcinomaimmune checkpoint inhibitorsperipheral blood indicatorsprogression-free survivalprognostic model
NETL
NSTL
万方数据
