Data Sheet 5_The neoadjuvant immunotherapy for non-metastatic mismatch repair-deficient colorectal cancer: a systematic review.pdf

BackgroundImmunotherapy has become the first-line treatment for metastatic mismatch repair deficient (dMMR) colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic dMMR colorectal cancer remain unclear. In this article, we explore the clinical effect and safety of neoadjuvant immunotherapy for non-metastatic dMMR colorectal cancer.
MethodsWe collected clinical data from the databases (PubMed, Wanfang Embase, Cochrane Library, and China National Knowledge Infrastructure databases) up to November 2024. The primary outcomes of major pathological response (MPR), pathological complete response (pCR), and other outcomes were analyzed for the final results. The secondary outcomes (pCR rates for the subgroups) were also analyzed.
ResultsWe included 21 articles with 628 non-metastatic dMMR colorectal cancers. A pCR was found in 320/480 (66.6%) patients [effect size (ES): 0.70, 95% CI: 0.66 to 0.74] with the fixed-effects model and little heterogeneity. A MPR was found in 388/452 (85.8%) patients (ES: 0.86, 95% CI: 0.81 to 0.91) with the fixed-effects model and little heterogeneity. In the subgroup analysis, pCR rates were similar in the T1-T3 group and T4a-T4b group in the fixed-effects model with minimal heterogeneity (OR: 0.76, 95% CI: 0.48 to 1.22). The pCR rates were similar in the colon cancer group and rectal cancer group in the fixed-effects model with minimal heterogeneity (OR: 1.41, 95% CI: 0.39 to 5.12). Similar pCR rates were found in the immune monotherapy group and immune therapy plus chemotherapy group (OR: 0.74, 95% CI: 0.26 to 2.10) with the fixed-effects model and little heterogeneity.
ConclusionNeoadjuvant immunotherapy achieves high rates of pCR and MPR for non-metastatic dMMR colorectal cancer. For locally advanced T4 stage dMMR colorectal cancer, neoadjuvant immunotherapy can still achieve good pCR rates. Neoadjuvant immune monotherapy can achieve good pCRs rates, avoiding the toxic side effects caused by combined dual immunotherapy and chemo(radio)therapy. Neoadjuvant immunotherapy could be another treatment option for non-metastatic dMMR colorectal cancer.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024594173.

研究背景：免疫治疗已成为转移性错配修复缺陷（dMMR）结直肠癌的一线治疗方案。然而，新辅助免疫治疗用于非转移性dMMR结直肠癌的疗效与安全性尚未明确。本文旨在探讨新辅助免疫治疗在非转移性dMMR结直肠癌中的临床疗效与安全性。
研究方法：本研究检索了截至2024年11月的PubMed、万方、Embase、Cochrane图书馆及中国知网（CNKI）数据库中的临床数据。最终分析的主要结局指标包括主要病理缓解（MPR）、病理完全缓解（pCR）及其他相关结局，同时也对次要结局指标（亚组pCR率）进行了分析。
研究结果：本研究共纳入21篇文献，涉及628例非转移性dMMR结直肠癌患者。采用固定效应模型分析显示，480例患者中320例达到pCR（占比66.6%），效应量（ES）为0.70，95%置信区间（CI）为0.66~0.74，异质性极低。452例患者中388例达到MPR（占比85.8%），效应量（ES）为0.86，95%置信区间（CI）为0.81~0.91，同样异质性极低。亚组分析结果显示，在固定效应模型下，T1~T3期组与T4a~T4b期组的pCR率无显著差异（比值比（OR）=0.76，95%CI=0.48~1.22），异质性极小；结肠癌亚组与直肠癌亚组的pCR率亦无显著差异（OR=1.41，95%CI=0.39~5.12），异质性极小。免疫单药治疗组与免疫联合化疗组的pCR率同样无显著差异（OR=0.74，95%CI=0.26~2.10），固定效应模型下异质性极低。
研究结论：新辅助免疫治疗可使非转移性dMMR结直肠癌患者获得较高的pCR与MPR率。对于局部进展期T4期dMMR结直肠癌，新辅助免疫治疗仍可获得良好的pCR率。新辅助免疫单药治疗可达到理想的pCR率，同时避免双免疫联合治疗及放化疗带来的毒副作用。新辅助免疫治疗有望成为非转移性dMMR结直肠癌的另一治疗选择。
系统评价注册信息：https://www.crd.york.ac.uk/prospero/，注册编号CRD42024594173。