Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, No.52, Fucheng Road, Haidian District, 100142, Beijing, China.
Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute, No.52, Fucheng Road, Haidian District, 100142, Beijing, China.
Eur J Surg Oncol. 2020 Oct;46(10 Pt B):e33-e39. doi: 10.1016/j.ejso.2020.06.034. Epub 2020 Jun 24.
Immune checkpoint inhibitors (ICIs) have been approved for the late-line treatment of unresectable gastrointestinal tumors, but their efficacy and safety in the neoadjuvant setting have not been described. Whether dMMR/MSI-H populations benefit from preoperative ICIs plus surgery remains undefined.
Six consecutive patients managed at our institution received neoadjuvant ICIs and surgery for advanced, resectable, and MSI-H gastrointestinal tumors. All patients underwent thorough clinical evaluations and radiographic investigations before and during treatment. Next-generation sequencing (NGS), immunohistochemical (IHC) staining, and in situ hybridization (ISH) were also performed for each patient' s biopsy section to generate their molecular profiling.
Neoadjuvant immunotherapy was efficient and well-tolerated in patients with dMMR/MSI-H gastrointestinal tumors. Pathologic responses were observed in 6/6 (100%) dMMR/MSI-H tumors, with 5/6 (83%) complete responses. The other patient was also confirmed to demonstrate a TNM downstaging after treated with ICIs. Three patients (50%) developed grade I/II adverse events. All enrolled patients underwent timely operations without the occurrence of unexpected perioperative or postoperative complications. No disease recurrence was identified during the follow-up so far.
Neoadjuvant immunotherapy results in favorable pathologic responses and minor adverse effects among patients with MSI-H gastrointestinal tumors. This pre-operative measure does not compromise subsequent surgery. There is an urgent need to warrant large-cohort clinical trials to examine the utility of neoadjuvant ICIs in resectable, dMMR/MSI-H gastrointestinal malignancies.
免疫检查点抑制剂（ICIs）已被批准用于不可切除胃肠道肿瘤的晚期治疗，但它们在新辅助治疗环境中的疗效和安全性尚未得到描述。术前 ICIs 联合手术是否能使错配修复缺陷/微卫星高度不稳定（dMMR/MSI-H）人群获益仍未明确。
本机构连续收治了 6 例接受新辅助 ICIs 联合手术治疗的晚期、可切除、MSI-H 胃肠道肿瘤患者。所有患者在治疗前和治疗期间均接受了全面的临床评估和影像学检查。还对每位患者的活检切片进行了下一代测序（NGS）、免疫组织化学（IHC）染色和原位杂交（ISH），以生成其分子谱。
dMMR/MSI-H 胃肠道肿瘤患者接受新辅助免疫治疗有效且耐受性良好。在 6/6（100%）dMMR/MSI-H 肿瘤中观察到病理缓解，其中 5/6（83%）完全缓解。另一位患者在接受 ICI 治疗后也被证实存在 TNM 降级。3 名患者（50%）发生 1/2 级不良事件。所有入组患者均及时进行了手术，无意外围手术期或术后并发症发生。随访至今，无疾病复发。
新辅助免疫治疗可使 MSI-H 胃肠道肿瘤患者获得良好的病理缓解和较小的不良反应。这种术前措施不影响随后的手术。迫切需要进行大规模的临床试验来检验新辅助 ICIs 在可切除、dMMR/MSI-H 胃肠道恶性肿瘤中的应用价值。
