Total Neoadjuvant Therapy With PD-1 Blockade for High-Risk Proficient Mismatch Repair Rectal Cancer

作者：Yingjie Li, Chaohu Pan, Yuye Gao, Li Zhang, Dengbo Ji, Xiaoli Cui, Xiaoyan Zhang, Yong Cai, Yangzi Zhang, Yunfeng Yao, Lin Wang, Jiahua Leng, Tiancheng Zhan, Dongfang Wu, Zhibo Gao, Ying‐Shi Sun, Zhongwu Li, Haitao Luo, Aiwen Wu · 发表于：JAMA Surgery · 年份：2024 · DOI：10.1001/jamasurg.2023.7996 · 被引用次数：50 · 研究领域：Colorectal Cancer Surgical Treatments、Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers

Importance: Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. Objectives: To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. Design, Setting, and Participants: This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Interventions: Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. Main Outcomes and Measures: The primary end point was pathologic complete response rate. Results: Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (...