Liu D, Wang H, Yuan Z X, Chen W W, Wu Z J, Liu X X, Luo J, Chu L L, Li Y, Cai J
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Institute of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Mar 25;24(3):256-263. doi: 10.3760/cma.j.cn.441530-20201111-00604.
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. 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 test and I(2) statistics. When there was no significant heterogeneity ( test: ≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed ( test: <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 (<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. 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 (=0.024, (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: =0.255, (2)=22.9%; PC control group: =0.222, (2)=29.9%; CRS+IPC control group: =0.947, (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 (=0.088) >0.05 and Egger's test (=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. CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.
探讨减瘤手术联合腹腔热灌注化疗(CRS+HIPEC)能否提高结直肠癌腹膜转移患者的生存率。从PubMed、Embase、Cochrane图书馆、中国知网、万方、维普数据库系统检索相关研究,并手动检索法国Elias团队关于腹膜转移的研究。纳入标准:(1)患者为结直肠癌腹膜转移。(2)有CRS+HIPEC治疗(治疗组)和其他治疗(对照组)。(3)有治疗组和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)文献为中文或英文。排除标准:(1)无全文的研究;(2)数据不完整的研究。由两人独立进行文献筛选和数据提取,第三人对有分歧的文献进行裁决。提取的数据包括作者、发表年份、患者数量、入组时间、随访时间、研究设计、治疗方案、治疗组和对照组的风险比(HR)及95%可信区间(CI)。若文献中未提供治疗组和对照组的HR及95%CI,则使用Engauge Digitizer 11.1软件从两组的生存曲线中提取随访时间及相应时间点的生存率,并结合两组人数计算两组的HR及95%CI。采用纽卡斯尔-渥太华量表(NOS)或Cochrane协作网的风险偏倚评估工具对研究质量进行评估。使用STATA 15.1软件进行统计分析。对两组的HR及95%CI进行合并分析。通过 检验和I²统计量评估试验间异质性。当无显著异质性( 检验:≥0.10)时,采用固定效应模型进行合并分析。当存在显著异质性( 检验:<0.10)时,采用随机效应模型进行合并分析,并进行亚组分析以找出异质性来源。采用敏感性分析评估合并结果的稳定性。通过Egger检验和Begg检验评估发表偏倚(<0.05表示存在发表偏倚),并通过Begg漏斗图在HR自然对数上的视觉对称性来反映。本Meta分析共纳入10项研究,其中1项随机对照试验,9项队列研究。1项随机对照试验的偏倚风险不确定,9项队列研究均高于7分,表明文献质量较高。治疗组781例患者接受CRS+HIPEC,对照组2452例患者接受其他治疗,包括肿瘤减瘤手术(CRS)、姑息化疗(PC)和腹腔内化疗(IPC)。随机效应模型合并分析结果显示,治疗组总生存率显著高于对照组(HR=0.43,95%CI:0.34-0.54),但研究异质性较高( =0.024,I²=52.9%)。不同对照治疗的亚组分析显示,治疗组总生存率显著高于CRS对照组(HR=0.63,95%CI:0.44-0.90)、PC对照组(HR=0.37,95%CI:0.32-0.43)、CRS+IPC对照组(HR=0.60,95%CI:0.37-0.96),各亚组异质性均较低(CRS对照组: =0.255,I²=22.9%;PC对照组: =0.222,I²=29.9%;CRS+IPC对照组: =0.947,I²=0)。由于亚组异质性较低,采用固定效应模型进行合并分析。敏感性分析结果显示,每项研究删除后合并分析结果差异不大,提示合并分析结果较为可靠。各研究的发表偏倚检测显示,Begg检验( =0.088)>0.05,Egger检验( =0.138)>0.05。根据Begg漏斗图,散点分布基本对称,表明纳入研究不存在发表偏倚。CRS+HIPEC可提高结直肠癌腹膜转移患者的总生存率。