治疗前系统性全身免疫炎性指标和乳酸脱氢酶对鼻咽癌预后的预测价值

Prognostic value of pretreatment systemic immune-inflammation index and lactate dydrogenasein nasopharyngeal carcinoma

目的探讨治疗前系统性免疫炎性指标(SII)、乳酸脱氢酶(LDH)对非转移性鼻咽癌预后的预测价值。方法纳入2007年1月至2015年10月就诊于中国医学科学院肿瘤医院和中山大学肿瘤防治中心的非转移性鼻咽癌患者839例,均接受调强放疗(IMRT)为主的治疗。使用X-title软件确定SII和LDH预测鼻咽癌患者5年总生存的最佳界值,分析SII、LDH与临床特征的关系。生存分析采用Kaplan-Meier法,组间生存率的比较采用Log rank检验。生存时间影响因素分析采用单因素及多因素Cox模型回归分析。为排除混杂因素对预后的影响,行倾向性评分匹配(PSM)分析。构建包含N分期、SII、LDH的预后风险分层模型,比较高危组、中危组、低危组患者的预后,采用受试者工作特性(ROC)曲线分析评估其预后预测价值。结果SII预测鼻咽癌患者5年总生存的最佳界值为447.2×10^(9)/L,LDH的最佳界值为198.9 U/L。高SII组中T3~4期、Ⅲ~ⅣB期患者的比例高于低SII组(均P<0.001)。多因素Cox回归分析显示,N分期、SII和LDH均为鼻咽癌患者总生存时间(OS)、无进展生存时间(PFS)、无远处转移生存时间(DMFS)的独立影响因素[N分期:HR=1.705,95%CI为1.247~2.332;HR=1.755,95%CI为1.342~2.295;HR=2.161,95%CI为1.515~3.082。SII:HR=1.525,95%CI为1.097~2.119;HR=1.518,95%CI为1.150~2.004;HR=1.837,95%CI为1.272~2.653。LDH:HR=2.041,95%CI为1.403~2.968;HR=1.725,95%CI为1.233~2.414;HR=2.492,95%CI为1.690~3.672]。经过PSM后,SII仍然是鼻咽癌患者OS、PFS、DMFS的独立影响因素(HR=1.52,95%CI为1.09~2.12;HR=1.52,95%CI为1.15~2.00;HR=1.82,95%CI为1.26~2.63)。将N分期为N2~3期、SII>447.2×10^(9)/L、LDH>198.9 U/L作为危险因素,有0~1个危险因素的患者为低危组,有2个危险因素的患者为中危组,有3个危险因素的患者为高危组。低危组、中危组和高危组患者的5年总生存率分别为86.1%、79.8%和41.2%,5年无进展生存率分别为80.7%、70.2%和33.9%,5年无远处转移生存率分别为88.9%、79.2%和47.5%,3组间差异均有统计学意义(均P<0.001)。低危组、中危组和高危组患者主要的治疗失败模式均为远处转移,高危组远处转移率最高,为83.3%(15/31)。所构建的预后风险分层模型预测鼻咽癌患者5年总生存的ROC曲线下面积为0.610,高于TNM分期(0.609)、SII(0.574)、LDH(0.558)。结论非转移性鼻咽癌治疗前血液中SII、LDH与患者预后密切相关,联合SII、LDH和N分期将鼻咽癌患者进行预后风险分层可提高预后预测的准确性。

Objective To evaluate the prognostic value of pretreatment systemic immune-inflammation index(SII)and lactate dehydrogenase(LDH)in non-metastatic nasopharyngeal carcinoma(NPC).Methods We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015.All patients received intensity modulated radiation based treatment.Optimal cutoff value of SII and LDH were determined by X-title software.The association between SII,LDH and clinical prognosis of non-metastatic NPC patients were analyzed.Kaplan-Meier method was used for survival analysis,and Log rank test was used for comparison of survival rates between groups.Propensity score matching(PSM)analysis was carried out to minimize the effects of confounding factors.The risk stratification model of prognosis by combining N stage,SII and LDH was constructed to compare the prognosis of patients in high risk group,middle risk group and low risk group,and the receiver operating characteristic(ROC)curve analysis was used to evaluate its prognostic value.Results The optimal cutoff value of SII is 447.2×10^(9)/L for predicting the 5-year overall survival(OS)of NPC patients,and the best cutoff value of LDH is 198.9 U/L.The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group(P<0.001).Multivariate Cox regression analysis showed that N stage,SII and LDH were independent factors of OS,progression-free survival(PFS)and distant metastasis-free survival(DMFS)of NPC patients(N stage,HR=1.705,95%CI:1.247-2.332;HR=1.755,95%CI:1.342-2.295;HR=2.161,95%CI:1.515-3.082.SII,HR=1.525,95%CI:1.097-2.119;HR=1.518,95%CI:1.150-2.004;HR=1.837,95%CI:1.272-2.653.LDH,HR=2.041,95%CI:1.403-2.968;HR=1.725,95%CI:1.233-2.414;HR=2.492,95%CI:1.690-3.672,respectively).After PSM,SII was still an independent prognostic factor of OS,PFS and DMFS in NPC patients(HR=1.52,95%CI:1.09-2.12;HR=1.52,95%CI:1.15-2.00;HR=1.82,95%CI:1.26-2.63,respectively).Combined with N 2-3 stage,SII(>447.2×10^(9)/L),and LDH(>198.9 U/L),patients were divided into high-(3 risk factors),intermediate-(2 risk factors)and low-risk(0-1 risk factors)groups.The 5-year OS rates of patients in low-,intermediate-and high-risk groups were 86.1%,79.8%and 41.2%respectively,the 5-year PFS rates were 80.7%,70.2%and 33.9%respectively,and the 5-year DMFS rates were 88.9%,79.2%and 47.5%respectively.There were significant differences in OS,PFS and DMFS among these three groups(P<0.001).Distant metastasis was the main failure pattern in low-,intermediate-and high-risk groups,and the highest rate of distant metastasis was 83.3%(15/31)in high-risk group.ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610,which is higher than TNM stage(0.609),SII(0.574)and LDH(0.558).Conclusions Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC.The combination of SII,LDH and N stage can stratify the prognostic risk of NPC patients.The risk stratification model can enhance the accuracy of prognosis.