[Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis]
- PMID: 34645170
- DOI: 10.3760/cma.j.cn.441530-20201111-00604
[Meta analysis of whether cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy can improve survival in patients with colorectal cancer peritoneal metastasis]
Abstract
Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.
目的: 探究肿瘤细胞减灭术(CRS)联合腹腔热灌注化疗(HIPEC)能否提高结直肠癌腹膜转移患者的生存率。 方法: 从PubMed、Embase、Cochrane Library以及CNKI、万方、维普六个数据库中检索腹膜转移的相关文献,并手动检索了法国Elias团队关于腹膜转移的研究。文献纳入标准:(1)研究对象为结直肠癌腹膜转移患者;(2)有接受CRS+HIPEC治疗为试验组和接受其他治疗为对照组的资料;(3)有试验组与对照组的生存分析数据;(4)研究类型为随机对照试验、队列研究或病例对照研究;(5)文献语言为中文和英文。排除标准:(1)仅有摘要的研究;(2)数据不全的研究。文献的筛选和数据提取由两人独立进行,存在分歧的文献由第三人决定。提取的数据包括作者、发表年份、受试者数量、受试者的入组时间、随访时间、研究设计、治疗方案,以及试验组和对照组的风险比HR及其95% CI,若文中未提供,则通过Engauge Digitizer11.1软件从生存曲线中提取随访时间和相应时间点的生存率,计算HR及其95% CI。采用Cochrane风险偏倚评估工具或纽卡斯尔-渥太华量表对文献进行质量评估。使用STATA15.1软件进行统计分析。对所有研究中试验组与对照组的HR及其95% CI进行合并分析,试验间异质性通过Q检验和I(2)统计量进行评估。当不存在显著异质性时(Q检验:P≥0.10),采用固定效应模型合并分析。当存在显著的异质性时(Q检验:P<0.10),采用随机效应模型合并分析,并通过亚组分析找出异质性的来源。用敏感性分析评价合并结果的稳定性。通过Egger检验和Begg检验来评估发表偏倚(P<0.05表示存在发表偏倚),并通过Begg漏斗图在风险比对数上的视觉对称性来反映。 结果: 共有10项研究被纳入进行Meta分析,包括1项随机对照试验、9项队列研究,1项随机对照试验偏倚风险不确定;9项队列研究文献质量评分均>7分,均为高质量研究。其中试验组有781例结直肠癌腹膜转移患者,对照组有2 452例接受了其他治疗[包括肿瘤细胞减灭术(CRS)、姑息化疗(PC)和腹腔内化疗(IPC)]。合并结果显示,试验组总体生存率(OS)高于其他治疗对照组(HR=0.43,95% CI:0.34~0.54),但研究异质性较大(P=0.024,I(2)=52.9%)。不同对照治疗方案的亚组分析结果显示,试验组OS高于CRS(HR=0.63,95% CI:0.44~0.90)、PC(HR=0.37,95% CI:0.32~0.43)和CRS+IPC(HR=0.60,95% CI:0.37~0.96)这3个对照组;由于各亚组研究异质性较低(CRS组:P=0.255,I(2)=22.9%;PC组:P=0.222,I(2)=29.9%;CRS+IPC组:P=0.947,I(2)=0),故采用固定效应模型对结果进行合并。敏感性分析结果显示,分别删除各项研究后的合并分析结果差别不大,提示合并分析结果较为可靠。各研究偏倚检测结果显示:Begg检验(P=0.088)>0.05,Egger检验(P=0.138)>0.05,Begg漏斗图上的散点分布基本对称,表明纳入研究不存在发表偏倚。 结论: CRS+HIPEC可以提高结直肠癌腹膜转移患者的OS。.
Keywords: Colorectal neoplasms; Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; Meta analysis; Peritoneal metastasis.
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