为了对正在实施的紫龙金片治疗非小细胞肺癌的前瞻性真实世界研究数据进行中期分析,初步评估紫龙金片改善患者临床结局的可能优势,采用前瞻性注册登记研究设计,招募确诊为非小细胞肺癌的患者,依据是否使用过紫龙金片区分为暴露组和非暴露组。选择其中随访时长超过18个月的患者数据,采用倾向性评分匹配对重要临床因素进行控制,对患者生存时间数据进行生存分析,采用Kaplan-Meier法计算估计生存率,采用Cox比例风险回归模型估算2组间的风险比(HR),比较2组人群的终点事件发生率、估计生存率、体力状态和生活质量评分。结果表明:暴露组死亡和失访发生率在匹配前后均低于非暴露组(P<0.05)。生存分析显示匹配前后暴露组估计生存率高于非暴露组,其中第18个月2组估计生存率匹配前分别为0.872和0.823,匹配后分别为0.865和0.816。2组生存曲线具有显著差异(P<0.05),匹配前后HR分别为0.661和0.474。匹配前后在第6个月和第18个月访视点时,暴露组美国东部肿瘤协作组体力状态评分(ECOG-PS)评分0分的比例较高(P<0.05)。匹配后在第6个月访视点时暴露组欧洲五维健康量表健康状况视觉模拟评分(EQ-VAS)显著高于非暴露组(P<0.05)。研究结果证明紫龙金片的临床应用能降低非小细胞肺癌患者的死亡终点发生率,提高患者生存率,并在维持患者体力状态和生活质量评分方面表现出优于非暴露组的趋势。
刘强
,
于明薇
,
吴万垠
,
郭勇
,
陈军
,
贺宇彤
,
薛文翰
,
张洪珍
,
郭秋香
,
杨国旺
,
张怡
,
游佳凤
,
杨永
,
高宠
,
念家云
,
何丽云
,
王笑民
. 紫龙金片对非小细胞肺癌患者临床结局影响的真实世界研究[J]. 科技导报, 2023
, 41(14)
: 82
-91
.
DOI: 10.3981/j.issn.1000-7857.2023.14.010
To conduct an interim analysis on the data of an ongoing prospective real world study of Zilongjin tablet in the treatment of non-small cell lung cancer (NSCLC), and preliminarily evaluate the potential advantages of Zilongjin tablets in improving clinical outcomes of patients, a prospective registry study was designed to enroll patients with NSCLC. The patients were divided into exposure group and non-exposure group according to using Zilongjin tablets for treatment. Analysis was focused on the subjects been followed up for more than 18 months, and propensity score matching was adopted to control confounding factors. Kaplan-Meier method was used to calculate the estimated survival rate, Cox proportional risk regression model was used to estimate the risk ratio between the two groups, and the incidence of end events, estimated survival rate, physical strength and quality of life scores were compared between groups. The mortality and loss of follow-up in exposure group was lower than that in non-exposure group before and after matching (P<0.05). The survival analysis showed that the estimated survival rate of the exposure group before and after matching was higher than that of the non-exposure group. The estimated survival rates of the two groups at the 18th month were 0.872 and 0.823 before the match, and 0.865 and 0.816 after matching, respectively. There was a significant difference in the survival curve between the two groups (P<0.05). The risk ratio (HR) before and after matching was 0.661 and 0.474, respectively. For ECOG-PS score before and after matching, the proportion of zero point in exposure group at the 6th and 18th month was higher (P<0.05). After matching, the EQ-VAS of exposure group was significantly higher than that of non-exposure group at the 6th month (P<0.05). The clinical application of Zilongjin tablets can reduce the incidence of death end points and improve the survival rate of patients with non-small cell lung cancer. Compared with the non-exposure group, it also showed potential advantages in maintaining patients' physical strength and quality of life scores.
[1] 国家卫生健康委办公厅 . 原发性肺癌诊疗指南(2022 年版)[J]. 协和医学杂志, 2022, 13(4): 549-570.
[2] 游佳凤, 于明薇, 杨国旺 . 紫龙金片临床应用及相关机理研究进展[J/OL]. 世界科学技术-中医药现代化 .[2022-12-18]. http://kns.cnki.net/kcms/detail/11.5699.R.20221027.1844.004.html.
[3] 林洪生, 李萍萍, 薛冬, 等. 肿瘤姑息治疗中成药使用专家共识(2013 版)[J]. 中国中西医结合杂志, 2016, 36(3): 269-279.
[4] 叶思思, 肖祖林, 任真, 等. 紫龙金片联合化疗治疗非小细胞肺癌的疗效及安全性 Meta 分析[J]. 中医药导报, 2020, 26(5): 97-102.
[5] 刘春香, 王辉, 翟静波, 等. 紫龙金治疗非小细胞肺癌的系统评价[J]. 辽宁中医杂志, 2013, 40(12): 2448-2453, 2637.
[6] 于明薇, 刘强, 张怡, 等. 紫龙金片治疗肺癌的真实世界数据回顾性研究[C]//第十七届全国中西医结合肿瘤学术大会摘要集. 上海: 中国中西医结合学会肿瘤专业委员会, 2019: 126.
[7] 于明薇, 刘强, 吴万垠, 等. 基于多中心真实世界数据的紫龙金片辅助治疗肺癌患者生存分析[J]. 中草药, 2022, 53(12): 3730-3739.
[8] Neeman E, Gresham G, Ovasapians N, et al. Comparing physician and nurse eastern cooperative oncology group performance status (ecog-ps) ratings as predictors of clinical outcomes in patients with cancer[J]. Oncologist, 2019, 24(12): e1460-e1466.
[9] Krishnan M, Temel J S, Wright A A, et al. Predicting life expectancy in patients with advanced incurable cancer: A review[J]. The Journal of Supportive Oncology, 2013, 11(2): 68-74.
[10] 李明晖, 罗南 . 欧洲五维健康量表(EQ-5D)中文版应用介绍[J]. 中国药物经济学, 2009(1): 49-57.
[11] Liu G G, Wu H, Li M, et al. Chinese time trade-off values for EQ-5D health states[J]. Value in Health, 2014, 17(5): 597-604.
[12] 史钊, 李顺平, 扎西达娃, 等. EQ-5D-3L量表两种中国效用积分体系的比较: 基于西藏城乡居民的应用[J]. 中国卫生经济, 2019, 38(12): 9-12.
[13] 柏柳安宁, 夏结来, 王陵, 等 . 真实世界研究中的常见偏倚及其控制[J]. 中国临床药理学与治疗学, 2020, 25(12): 1422-1428.
[14] 中医真实世界研究技术规范通则: T/CACM 022—2017[S]. 北京: 中华中医药学, 2017.
[15] Zhang P, Wang X, Xiong S, et al. Genome wide expression analysis of the effect of the Chinese patent medicine Zilongjin tablet on four human lung carcinoma cell lines[J]. Phytotherapy Research, 2011, 25(10): 1472-1479.
[16] 王代树, 施学东, 梁云燕, 等 . 中药白龙与 HMBA 对人癌周期细胞CKI-P16的调控[J]. 中国中西医结合杂志, 2001(10): 763-766.
[17] 史东升, 周静敏, 马淑萍 . 紫龙金对人非小细胞肺癌A549 细胞生长及 VEGF 表达的影响[J]. 中国肿瘤临床, 2011, 38(20): 1267-1270.
[18] 谢远平, 田宁, 宁华, 等 . 基于网络药理学和分子对接的紫龙金片治疗肺癌的作用机制研究[J/OL]. [2022-12-18]. http://kns.cnki.net/kcms/detail/21.1128.R.20220815.1820.126.html.
[19] 陈吉, 孙月, 布优祥, 等 . 中医领域真实世界研究现状分析[J]. 中国循证医学杂志, 2018, 18(11): 1216-1223.
[20] 张妮楠, 史华新, 周洪伟, 等 . 中医真实世界研究的特征探析[J]. 世界科学技术-中医药现代化, 2018, 20(9): 1496-1500.
[21] 叶晓勤, 谢雁鸣, 王利娜, 等 . 倾向性评分法在中医复杂干预非随机化数据疗效评价中的应用[J]. 中华中医药杂志, 2015, 30(10): 3414-3417.
[22] 焦明旭, 张晓, 刘迪, 等 . 倾向性评分匹配在非随机对照研究中的应用[J]. 中国卫生统计, 2016, 33(2): 350-352.
[23] 黎国威, 张玲, 陈裕明, 等 . 倾向性评分方法在观察性研究中的应用[J]. 中国循证医学杂志, 2021, 21(4): 469-474.