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J Clin Oncol. 2023 Jan 10;41(2):255-265. doi: 10.1200/JCO.22.00686. Epub 2022 Aug 15.
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Combination of AKT1 and CDH1 mutations predicts primary resistance to immunotherapy in dMMR/MSI-H gastrointestinal cancer.AKT1 和 CDH1 突变的联合预测了错配修复缺陷/微卫星高度不稳定(dMMR/MSI-H)胃肠道肿瘤对免疫治疗的原发性耐药。
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Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial.托瑞帕利单抗新辅助PD-1阻断联合或不联合塞来昔布治疗错配修复缺陷或微卫星高度不稳定的局部晚期结直肠癌(PICC):一项单中心、平行组、非对照、随机、2期试验
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错配修复缺陷或微卫星高度不稳定的胃肠道恶性肿瘤患者术前免疫治疗的疗效与安全性

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies.

作者信息

Li Ying-Jie, Liu Xin-Zhi, Yao Yun-Feng, Chen Nan, Li Zhong-Wu, Zhang Xiao-Yan, Lin Xin-Feng, Wu Ai-Wen

机构信息

Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Gastro-intestinal Ward III, Beijing Cancer Hospital, Beijing 100142, China.

出版信息

World J Gastrointest Surg. 2023 Feb 27;15(2):222-233. doi: 10.4240/wjgs.v15.i2.222.

DOI:10.4240/wjgs.v15.i2.222
PMID:36896306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9988634/
Abstract

BACKGROUND

Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited.

AIM

To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy.

METHODS

In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle.

RESULTS

Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer.

CONCLUSION

Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

摘要

背景

程序性死亡蛋白(PD)-1阻断免疫疗法可显著延长转移性错配修复缺陷(dMMR)/微卫星高度不稳定(MSI-H)的胃肠道恶性肿瘤(如胃癌和结直肠癌)患者的生存期。然而,关于术前免疫疗法的数据有限。

目的

评估术前PD-1阻断免疫疗法的短期疗效和毒性。

方法

在这项回顾性研究中,我们纳入了36例dMMR/MSI-H胃肠道恶性肿瘤患者。所有患者术前接受了PD-1阻断治疗,部分患者联合CapOx方案化疗。每21天为一个周期,在第1天静脉注射200mg PD-1阻断剂,持续30分钟。

结果

3例局部晚期胃癌患者达到病理完全缓解(pCR)。3例局部晚期十二指肠癌患者达到临床完全缓解(cCR),随后采取观察等待策略。16例局部晚期结肠癌患者中有8例达到pCR。4例结肠癌肝转移患者均达到CR,其中3例为pCR,1例为cCR。5例非肝转移结直肠癌患者中有2例达到pCR。5例低位直肠癌患者中有4例达到CR,其中3例为cCR,1例为pCR。36例患者中有7例达到cCR,其中6例选择观察等待策略。胃癌或结肠癌患者未观察到cCR。

结论

术前对dMMR/MSI-H胃肠道恶性肿瘤患者进行PD-1阻断免疫疗法可实现较高的CR率,尤其是十二指肠或低位直肠癌患者,并且能实现较高的器官功能保护。