摘要
目的探讨上皮性卵巢癌(EOC)患者接受新辅助化疗(NACT)联合间歇性肿瘤细胞减灭术(CS)治疗后的预后情况,并对EOC患者血清学与影像学指标对初次肿瘤细胞减灭术(PCS)后肉眼可见病灶完全切除,无残留病灶(R0)的预测价值。方法选择2014年3月至2018年7月于四川大学华西第二医院接受NACT联合间歇性CS治疗的129例EOC患者为研究对象。根据PCS是否达R0,将其分别纳入R0组(n=72)与非R0组(n=57)。入院后,收集2组患者PCS前、后血清糖类抗原125(CA_(125))水平、中性粒细胞与淋巴细胞比值(NLR)、淋巴细胞与单核细胞比值(LMR)、血小板与淋巴细胞比值(PLR)等血清学指标,以及超声或CT检查的肿块最大径等影像学指标,分别采用CA_(125)-1、NLR-1、LMR-1、PLR-1、肿块最大径-1,以及CA_(125)-2、NLR-2、LMR-2、PLR-2、肿块最大径-2表示,对PCS前、后检查结果变化值,则采用CA_(125)-ratio、NLR-ratio、LMR-ratio、PLR-ratio、肿块最大径-ratio表示,并采用Mann-Whitney U检验进行比较。绘制血清学与影像学指标预测EOC患者PCS达R0的受试者工作特征(ROC)曲线,并确定其预测的最佳临界值,计算各指标单一与联合预测EOC患者PCS达R0的预测效能。采用Cox比例风险回归分析,对R0组与非R0组、不同周期NACT满足血清学与影像学指标联合诊断标准EOC患者的总体生存(OS)与无进展生存(PFS)率进行比较。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果①R0组患者的OS率(60.0%)较非R0组(28.6%)高,并且差异有统计学意义(HR=0.370,95%CI:0.194~0.703,P=0.002)。R0组PFS率(40.3%)与非R0组(54.4%)比较,差异无统计学意义(P=0.122)。②R0组与非R0组EOC患者CA_(125)-ratio、NLR-2和LMR-2分别比较,差异均有统计学意义(Z=-3.09、-2.14、-2.40,P=0.002、0.033、0.017),2组PLR-Ratio比较,差异无统计学意义(P=0.912)。③绘制CA_(125)-ratio、1-NLR-2、LMR-2及肿块最大径-ratio预测EOC患者PCS后是否达R0的ROC曲线结果显示,根据约登指数最大原则,预测EOC患者PCS后达R0的最佳临界值为CA_(125)-ratio>93.64%,NLR-2<2.14,LMR-2>4.34,此时其阳性预测值分别为71.0%、65.6%、68.2%;根据实体瘤疗效评价标准(RECIST)1.1,采用肿块最大径-ratio>20%预测EOC患者PCS后达R0的阳性预测值为62.9%。当患者满足CA_(125)-ratio>93.6%、NLR-2<2.14、LMR-2>4.34、肿块最大径-ratio>20%这4项指标中≥3项或4项时,其预测EOC患者PCS后达R0的阳性预测值分别为75.7%与88.2%。④Cox比例风险回归分析结果显示,对不同周期NACT(<3个、3个与>3个周期)满足上述≥3项指标EOC患者的OS曲线比较,差异无统计学意义(P>0.05),但是随着NACT周期增加,EOC患者OS率呈下降趋势。结论采取NACT联合间歇性CS治疗EOC患者,PCS后达R0者OS率高于未达R0者。将CA_(125)-ratio>93.6%、NLR-2<2.14、LMR-2>4.34、肿块最大径-ratio>20%联合预测EOC患者NACT后进行PCS达R0的阳性预测值,较单一指标预测的阳性预测值更高。当EOC患者满足上述指标≥3项时,及时终止NACT可能有助于患者获得更高OS率。
Objective To investigate the prognosis of neoadjuvant chemotherapy(NACT)combined with interval cytoreductive surgery(CS)in treatment of patients with epithelial ovarian cancer(EOC),and analyze the predictive value of serological and imaging indicators in EOC patients for reaching macroscopic residual lesion naught(R0)after primary cytoreductive surgery(PCS).Methods A total of 129 EOC patients who underwent NACT combined with interval CS in West China Second University Hospital,Sichuan University from March 2014 to July 2018 were enrolled as research subjects.Patients were enrolled into R0 group(n=72)and non-R0 group(n=57)according to whether the patients reached R0 after PCS.The serological indicators of two groups were collected,including the serum level of carbohydrate antigen 125(CA_(125)),neutrophil-to-lymphocyte ratio(NLR),lymphocyte-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and the image indicator(maximum diameter of tumor on ultrasound or CT examination)of patients before and after PCS.Results of examinations before PCS was recorded as CA_(125)-1,NLR-1,LMR-1,PLR-1 and maximum diameter-1,and results of examinations after PCS was recorded as CA_(125)-2,NLR-2,LMR-2,PLR-2 and maximum diameter-2.The change values between them were recorded as CA_(125)-ratio,NLR-ratio,LMR-ratio,PLR-ratio,and maximum diameter-ratio.Mann-Whitney U test was used for comparison of these indicators between the R0 and non-R0 groups.The receiver operating characteristic(ROC)curve of serological and imaging indicators in predicting R0 in PCS of EOC patients was plotted,and the optimal cut-off value for prediction was determined.The prediction performance of single and combined indicators in predicting R0 in PCS of EOC patients was calculated.Cox proportional hazards regression analysis was used to compare the overall survival(OS)and progression-free survival(PFS)curves of EOC patients in the R0 and non-R0 groups and patients under different NACT cycles that met the combined diagnostic criteria of serological and imaging indicators.The procedures followed in this study were in line with the requirements of the World Medical Association Declaration of Helsinki revised in 2013.Results①The OS rate of R0 group(60.0%)was higher than that of non-R0 group(28.6%),and the difference was statistically different(HR=0.370,95%CI:0.194-0.703,P=0.002).There was no significant difference in PFS rate between R0 group(40.3%)and non-R0 group(54.4%)(P=0.122).②The differences in CA_(125)-ratio,NLR-2 and LMR-2 between R0 group and non-R0 group were statistically significant(Z=-3.09,-2.14,-2.40;P=0.002,0.033,0.017),but there was no significant difference in PLR-ratio between two groups(P=0.912).③Results of the ROC curve of CA_(125)-ratio,1-NLR-2,LMR-2 and maximum diameter-ratio for predicting R0 in PCS of EOC patients showed that the optimal cutoff value for prediction of achieve R0 was CA_(125)-ratio>93.64%,NLR-2<2.14,LMR-2>4.34 according to the principle of maximum Youden index,and their positive predictive values were 71.0%,65.6%,and 68.2%,respectively.According to response evaluation criteria in solid tumors(RECIST)1.1,maximum diameter-ratio>20%was used to predict R0 in PCS of EOC patients,and its positive predictive value was 62.9%.Combining these four indicators,when the patient met≥3 or 4 of CA_(125)-ratio>93.6%,NLR-2<2.14,LMR-2>4.34,and maximum diameter-ratio>20%,its positive predictive values of achieving R0 in EOC patients were 75.7%and 88.2%,respectively.④Results of Cox proportional hazards regression analysis showed that there was no significant difference in the OS curves of EOC patients with different NACT cycles(<3,3 and>3 cycles)that met≥3 of the above indicators(P>0.05),but with the increase of NACT cycles,the OS rate of EOC patients showed a downward trend.Conclusions The OS rate of EOC patients who reach R0 in PCS after NACT is higher than that of those who do not reach R0.The positive predictive value of combination of CA_(125)-ratio>93.6%,NLR-2<2.14,LMR-2>4.34 and maximum diameter-ratio>20%for prediction of R0 in EOC patients is higher than the positive predictive value predicted by a single indicator.When patients with EOC meet≥3 of the above indicators,the termination of NACT may help patients achieve higher OS rates.
作者
何欣林
阎昊铮
赵亦非
江彩霞
李征宇
He Xinlin;Yan Haozheng;Zhao Yifei;Jiang Cairia;Li Zhengyu(Department of Obstetrics and Gynecology,Key Laboratory of Birth Defects and Related Disease of Women and Children,Ministry of Education,Reproductive Endocrinology and Regulation Laboratory,West China Second University Hospital,Sichuan University,Chengdu 610041,Sichuan Province,China)
出处
《中华妇幼临床医学杂志（电子版）》
CAS
2024年第1期47-57,共11页
Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition)
基金
四川省自然科学基金项目(2023NSFSC0743)。
作者简介
通信作者:李征宇,Email:Zhengyuli01@126.com。
