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微卫星高度不稳定结直肠癌的免疫治疗

Immunotherapy for microsatellite-instability-high advanced colorectal cancer

摘要:

微卫星高度不稳定(MSI-H)结直肠癌约占所有结直肠癌患者的10%~15%,而晚期患者中MSI-H人群仅占5%。既往研究显示,早中期MSI-H结直肠癌预后佳,但晚期患者预后差,对化疗不敏感。程序性死亡蛋白-1(PD-1)抗体的出现显著改变了该人群的预后和治疗格局,不仅在后线治疗获得良好疗效,而且在一线治疗中疗效也显著优于传统的化疗联合靶向。如何克服原发和继发性耐药是提高MSI-H转移性结直肠癌疗效的关键问题,常用的方法包括更换化疗方案、联合其他免疫疗法、联合抗血管生成、以及局部治疗(手术、放疗、介入)等。值得注意的是,免疫治疗存在一定的终身毒性甚至致死性毒性反应,须严格把握新辅助免疫治疗的适应证。MSI-H优势人群接受新辅助免疫治疗后,可获得较高的病理完全缓解率和临床完全缓解(cCR)率。因此,对有强烈保肛意愿,新辅助免疫治疗后严格评价为cCR的MSI-H患者,等待观察策略为一部分中低位直肠癌提供了一个保全括约肌功能及改善长期生存质量的机会。结直肠癌领域辅助免疫治疗的研究也正在如火如荼地开展,其结果值得期待。

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abstracts:

Microsatellite instability-high (MSI-H) colorectal cancer accounts for approximately 10%-15% of all colorectal cancer patients, while in metastatic diseases the MSI-H population accounts for only 5% of patients. Previous studies have shown that early-stage MSI-H colorectal cancer patients have a good prognosis, but those with advanced disease have a poor prognosis and are not sensitive to chemotherapy. The advent of PD-1 antibodies has significantly improved the prognosis and changed treatment landscape in this population, not only achieving good outcomes in late-line therapy, but also significantly outperforming traditional chemotherapy combined with targeted therapy in first-line therapy. How to overcome primary and secondary drug resistance is a key issue in improving the outcome of MSI-H metastatic colorectal cancer, and commonly used approaches include changing chemotherapy regimens, combining with other immunotherapies, combining with anti-angiogenesis, and local treatments (surgery, radiotherapy, or interventional therapy). It is worth noting that immunotherapy has certain lifelong or even lethal toxicity, and the indications for neoadjuvant immunotherapy must be evaluated with caution. Neoadjuvant immunotherapy in MSI-H advantaged population can achieve high rates of pathological complete remission (pCR) and clinical complete remission (cCR). Therefore, for MSI-H patients with a strong intention to preserve anal sphincter and a strict evaluation of cCR after neoadjuvant immunotherapy, the Watch-and-Wait strategy offers an opportunity to preserve sphincter function and improve long-term survival quality in a subset of mid-to-low rectal cancers. Research on adjuvant immunotherapy in the field of colorectal cancer is also in full swing, and the results are worth waiting for.

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作者: 丁培荣 [1]
期刊: 《中华胃肠外科杂志》2022年25卷3期 199-204页 MEDLINEISTICPKUCSCD
栏目名称: 专题论坛
DOI: 10.3760/cma.j.cn441530-20220118-00025
发布时间: 2024-07-30
基金项目:
国家自然科学基金 National Natural Science Foundation of China
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