Zhening Zhang1, Siyuan Cheng1, Jifang Gong1, Ming Lu1, Jun Zhou1, Xiaotian Zhang1, Jian Li1, Lin Shen1, Zhi Peng2. 1. 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. 2. 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. Electronic address: zhipeng3@hotmail.com.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.