背景:微卫星不稳定性(MSI)状态和肿瘤浸润淋巴细胞(TIL)是结直肠癌的确定预后因素。先前评估TIL和MSI状态组合的研究确定了具有独特预后关联的不同结直肠癌亚型。然而,这些研究通常受到样本量的限制,特别是对于MSI高(MSI-H)肿瘤,并且没有现有证据的全面摘要。我们旨在回顾文献,以比较与来自整合MSI-TIL分类的结直肠癌患者的生存结局。
方法:在本系统综述和网络荟萃分析中,我们搜索了PubMed,Embase,Scopus,和没有语言限制的Cochrane图书馆,适用于1990年1月1日至2024年3月13日之间发表的文章。包括比较手术切除的结直肠癌患者的TIL(高或低)和MSI状态(MSI或微卫星稳定[MSS])的不同组合的患者队列。如果研究集中在新辅助治疗或其他免疫标志物如B细胞或巨噬细胞,则被排除。方法学质量评估使用纽卡斯尔-渥太华量表进行;数据评估和提取由两名审阅者独立进行。摘要估计是从已发表的报告中提取的。主要结果是总生存率,无病生存,和癌症特异性存活率。进行了频繁的网络荟萃分析,以比较每种结果的风险比(HR)和95%CI。MSI-TIL亚组根据P评分进行预后排序,偏见,量级,以及与每个结果关联的精确度。协议注册到PROSPERO(CRD42023461108)。
结果:在最初确定的302项研究中,系统评价包括21项研究(包括14028例患者),荟萃分析包括19项研究(13029例患者)。九项研究被确定为低偏倚风险,其余十项研究具有中等偏倚风险。MSI-TIL-高(MSI-TIL-H)亚型表现出更长的总生存期(HR0·45,95%CI0·34-0·61;I2=77·7%),无病生存率(0·43,0·32-0·58;I2=61·6%),和癌症特异性生存率(0·53,0·43-0·66;I2=0%),其次是MSS-TIL-H亚型(HR0·53,0·41-0·69;I2=77·7%),无病生存率(0·52,0·41-0·64;I2=61·6%),与MSS-TIL低肿瘤患者(MSS-TIL-L)相比,癌症特异性生存率(0·55,0·47-0·64;I2=0%)。MSI-TIL-L亚型患者的总生存期(0·88,0·66-1·18;I2=77·7%)和无病生存期(0·93,0·69-1·26;I2=61·6%)相似,但与MSS-TIL-L亚型相比,癌症特异性生存期(0·72,0·57-0·90;I2=0%)稍长。直接和间接证据的结果非常一致。
结论:这项网络荟萃分析的结果表明,仅在TIL-H结直肠癌患者中观察到更好的生存率,无论MSI或MSS状态如何。应进一步探索综合MSI-TIL分类作为早期结直肠癌临床决策的预测工具。
背景:德国研究委员会(HO5117/2-2)。
BACKGROUND: Microsatellite instability (MSI) status and tumour-infiltrating lymphocytes (TIL) are established prognostic factors in colorectal cancer. Previous studies evaluating the combination of TIL and MSI status identified distinct colorectal cancer subtypes with unique prognostic associations. However, these studies were often limited by sample size, particularly for MSI-high (MSI-H) tumours, and there is no comprehensive summary of the available evidence. We aimed to
review the literature to compare the survival outcomes associated with the subtypes derived from the integrated MSI-TIL classification in patients with colorectal cancer.
METHODS: In this systematic
review and network meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library without language restrictions, for articles published between Jan 1, 1990, and March 13, 2024. Patient cohorts comparing different combinations of TIL (high or low) and MSI status (MSI or microsatellite stable [MSS]) in patients with surgically resected colorectal cancer were included. Studies were excluded if they focused on neoadjuvant therapy or on other immune markers such as B cells or macrophages. Methodological quality assessment was done with the Newcastle-Ottawa scale; data appraisal and extraction was done independently by two reviewers. Summary estimates were extracted from published reports. The primary outcomes were overall survival, disease-free survival, and cancer-specific survival. A frequentist network meta-analysis was done to compare hazard ratios (HRs) and 95% CI for each outcome. The MSI-TIL subgroups were prognostically ranked based on P-score, bias, magnitude, and precision of associations with each outcome. The protocol is registered with PROSPERO (CRD42023461108).
RESULTS: Of 302 studies initially identified, 21 studies (comprising 14 028 patients) were included in the systematic
review and 19 (13 029 patients) in the meta-analysis. Nine studies were identified with a low risk of bias and the remaining ten had a moderate risk of bias. The MSI-TIL-high (MSI-TIL-H) subtype exhibited longer overall survival (HR 0·45, 95% CI 0·34-0·61; I2=77·7%), disease-free survival (0·43, 0·32-0·58; I2=61·6%), and cancer-specific survival (0·53, 0·43-0·66; I2=0%), followed by the MSS-TIL-H subtype for overall survival (HR 0·53, 0·41-0·69; I2=77·7%), disease-free survival (0·52, 0·41-0·64; I2=61·6%), and cancer-specific survival (0·55, 0·47-0·64; I2=0%) than did patients with MSS-TIL-low tumours (MSS-TIL-L). Patients with the MSI-TIL-L subtype had similar overall survival (0·88, 0·66-1·18; I2=77·7%) and disease-free survival (0·93, 0·69-1·26; I2=61·6%), but a modestly longer cancer-specific survival (0·72, 0·57-0·90; I2=0%) than did the MSS-TIL-L subtype. Results from the direct and indirect evidence were strongly congruous.
CONCLUSIONS: The findings from this network meta-analysis suggest that better survival was only observed among patients with TIL-H colorectal cancer, regardless of MSI or MSS status. The integrated MSI-TIL classification should be further explored as a predictive tool for clinical decision-making in early-stage colorectal cancer.
BACKGROUND: German Research Council (HO 5117/2-2).