程序性细胞死亡蛋白1抗体联合全程新辅助放化疗治疗高风险局部进展期中低位直肠癌患者的近期结局  

Short-term outcome of programmed cell death protein1(PD-1)antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high risk factors

作　　者：李英杰[1] 张丽 董秋石 蔡勇[3] 张扬子 王林[1] 姚云峰[1] 张晓燕[4] 李忠武[2] 李永恒[3] 孙应实[4] 王维虎 武爱文[1] Li Yingjie;Zhang Li;Dong Qiushi;Cai Yong;Zhang Yangzi;Wang Lin;Yao Yunfeng;Zhang Xiaoyan;Li Zhongwu;Li Yongheng;Sun Yingshi;Wang Weihu;Wu Aiwen(Gastrointestinal Cancer Center,Unit III,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China;Department of Pathology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China;Department of Radiation Oncology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China;Department of Radiology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室,胃肠肿瘤中心三病区,100142 [2]北京大学肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室病理科,100142 [3]北京大学肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室放疗科,100142 [4]北京大学肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室医学影像科,100142

出　　处：《中华胃肠外科杂志》2021年第11期998-1007,共10页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金(82173156);北京市医管中心临床医学发展专项"扬帆"计划重点培育项目(ZYLX202116)。

摘　　要：目的探讨程序性细胞死亡蛋白1(PD-1)抗体联合全程新辅助治疗对高风险局部进展期中低位直肠癌患者应用的安全性和可行性。方法采用描述性病例系列研究方法。回顾性分析2019年1月至2021年4月期间,在北京大学肿瘤医院胃肠肿瘤中心三病区24例接受PD-1联合全程新辅助放化疗的高风险局部进展期中低位直肠癌患者的临床资料。纳入标准:(1)经病理学确诊的直肠腺癌,患者年龄范围18~80岁;(2)内镜下肿瘤下缘距离肛缘≤10 cm;(3)美国东部肿瘤协作组(ECOG)体力状况评分0~1;(4)初始MRI局部分期为T3c、T3d、T4a和T4b,或壁外血管侵犯(EMVI)阳性,或mrN2,或直肠系膜筋膜(MRF)阳性;(5)治疗前无明确远隔转移证据;(6)无盆腔放疗史、直肠癌手术史或化疗史;(7)不伴需抗生素治疗的全身性感染以及免疫系统疾病。排除标准:(1)预期新辅助治疗后肿瘤仍不可切除;(2)过去5年内罹患过其他可能影响患者结局的恶性肿瘤或过去6个月发生过动脉栓塞性疾病;(3)接受过其他类型的抗肿瘤或试验性治疗;(4)孕期或哺乳期女性;(5)合并有其他疾病或精神状态异常;(6)即往接受过抗PD-1抗体等免疫治疗的患者。新辅助治疗包括3个阶段,即PD-1抗体(信迪利单抗200 mg,静脉滴注,每3周1次)联合CapeOx方案(奥沙利铂+卡培他滨)3周期;长疗程放疗(调强放疗GTV 50.6 Gy/CTV 41.8 Gy/22 f);放疗结束后CapeOx方案化疗2周期。第3阶段治疗结束后经过肿瘤疗效评估,行手术治疗或选择等待观察。分析其手术安全性、病理组织学改变及近期肿瘤学结局。结果24例患者中男性15例,女性9例,中位年龄65(47~78)岁,肿瘤下缘距离肛缘中位距离4(3~7)cm。肿瘤最大径中位值5.1(2.1~7.5)cm。cT_(3)和cT_(4)期分别为20例和4例;cN_(1)、cN_(2)a和cN_(2)b期分别为8例、5例和11例。MRF阳性10例,EMVI阳性10例。所有患者均为错配修复蛋白阳性表达(pMMR)。新辅助治疗期间,6例(2Objective Total neoadjuvant chemoradiotherapy is one of the standard treatments for locally advanced rectal cancer.This study aims to investigate the safety and feasibility of programmed cell death protein 1(PD-1)antibody combined with total neoadjuvant chemoradiotherapy in the treatment of locally advanced middle-low rectal cancer with high-risk factors.Methods A descriptive cohort study was conducted.Clinicopathological data of 24 patients with locally advanced middle-low rectal cancer with high-risk factors receiving PD-1 antibody combined with neoadjuvant chemoradiotherapy in Gastrointestinal Cancer Center,Unit III,Peking University Cancer Hospital between January 2019 and April 2021 were retrospectively analyzed.Inclusion criteria:(1)rectal adenocarcinoma confirmed by pathology;patient age of≥18 years and≤80 years;(2)the distance from low margin of tumor to anal verge≤10 cm under sigmoidoscopy;(3)ECOG performance status score 0-1;(4)clinical stage T3c,T3d,T4a or T4b,or extramural venous invasion(EMVI)(+)or mrN2(+)or mesorectal fasciae(MRF)(+)based on MRI;(5)no evidence of distant metastases;(6)no prior pelvic radiation therapy,no prior chemotherapy or surgery for rectal cancer;(7)no systemic infection requiring antibiotic treatment and no immune system disease.Exclusion criteria:(1)anticipated unresectable tumor after neoadjuvant treatment;(2)patients with a history of a prior malignancy within the past 5 years,or with a history of any arterial thrombotic event within the past 6 months;(3)patients received other types of antitumor or experimental therapy;(4)women who were pregnant or breast-feeding;(5)patients with any other concurrent medical or psychiatric condition or disease;(6)patients received immunotherapy(PD-1 antibody).The neoadjuvant therapy consisted of three stages:PD-1 antibody(sintilimab 200 mg,IV,Q3W)combined with CapeOx regimen for three cycles;long-course intensity modulated radiation therapy(IMRT)with gross tumor volume(GTV)50.6 Gy/CTV 41.8 Gy/22f;CapeOx regimen for two cycles after r

关 键 词：直肠肿瘤 局部进展期 错配修复蛋白正常/微卫星稳定 全程新辅助治疗 程序性细胞死亡蛋白1(PD-1)抗体 病理学完全缓解 临床完全缓解 

分 类 号：R735.37[医药卫生—肿瘤]