■转移性结直肠癌(mCRC)的治疗包括切除肝转移(LM),然而,没有经过验证的生物标志物确定最有可能受益于该手术的患者.这项荟萃分析旨在评估CRC癌症相关基因中最相关的分子改变的影响(即,RAS,BRAF,SMAD4,PIK3CA)作为LM切除手术治疗的mCRC患者的生存和疾病复发的预后标志物。
■进行了系统的文献综述,以确定报告有关接受完全肝切除的CRCLM患者的生存和/或复发数据的研究。根据RAS分层,BRAF,PIK3CA,和SMAD4突变状态。在荟萃分析中汇总了多变量分析的危险比(HR),并结合了各种混杂因素的调整策略。在许多数据库中进行了搜索,包括MEDLINE(PubMed),Embase,护理和相关健康文献累积指数(CINAHL)(EBSCO主机),和世界卫生组织全球指数药物,到3月18日,2022年。荟萃分析,社论,给编辑的信,病例报告,对其他原发性癌症的研究,对肝脏以外的原发性转移部位的研究,缺乏特定肿瘤结果变量或遗传数据的研究,非英语语言研究,排除了从肝转移切除术中省略残留疾病数据的研究。其余的47项研究总结在一个描述性表格中,该表格概述了每项研究的关键特征,并以图形方式呈现了最终结果。
■RAS突变状态与总生存期(OS)呈负相关(HR,1.68;95%CI,1.54-1.84)和无复发生存率(RFS)(HR,1.46;95%CI,1.33-1.61)。BRAF在OS(HR,2.64;95%CI,2.15-3.24)和RFS(HR,1.89;95%CI,1.32-2.73)和关于OS的SMAD4(HR,1.93;95%CI,1.56-2.38)和RFS(HR,1.95;95%CI,1.31-2.91)。对于PIK3CA,只有三项研究符合资格,与OS或RFS均无显著关联。
■RAS,BRAF,在接受结直肠癌根治性肝转移切除术的患者中,SMAD4与OS和RFS呈负相关。由于文献可用性有限,无法得出PIK3CA的结论。这些数据支持RAS的集成,BRAF,和SMAD4突变状态在结直肠癌肝转移手术决策中的作用。然而,我们必须考虑几个限制,主要是汇集了评估患者无病生存率(DFS)或RFS结果的研究结果;纳入具有微小残留疾病和未考虑的潜在混杂因素的患者,例如可切除性定义的可变性,化疗使用,以及生物学标志物与切除前后的药物治疗之间的潜在相互作用。
UNASSIGNED: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.
UNASSIGNED: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.
UNASSIGNED: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.
UNASSIGNED: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.