低风险直肠癌患者全程新辅助治疗后主动性等待观察及器官保留策略:一项前瞻性、单中心、单臂研究(PKUCH-R01)的初步报告  

Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer:early result from a prospective,single arm trial

作　　者：王林[1] 赵一鸣 孙婷婷[1] 徐渊莲 李士杰[2] 张晓燕[3] 蔡勇[4] 李永恒[4] 李忠武[5] 陈鹏举[1] 彭亦凡[1] 王维虎 武爱文[1] Wang Lin;Zhao Yiming;Sun Tingting;Xu Yuanlian;Li Shijie;Zhang Xiaoyan;Cai Yong;Li Yongheng;Li Zhongwu;Chen Pengju;Peng Yifan;Wang Weihu;Wu Aiwen(Department of Gastrointestinal Cancer,Unit III,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Bejing 100142,China;Endoscopy Center,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Bejing 100142,China;Department of Radiation Oncology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Bejing 100142,China;Department of Radiology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Bejing 100142,China;Department of Pathology,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Bejing 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内镜中心,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医学影像科,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放疗科,100142 [5]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

出　　处：《中华胃肠外科杂志》2020年第3期258-265,共8页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金(81773214);首都特色临床研究(Z15110004015105);北京市卫生系统215高层次人才项目(2016)。

摘　　要：目的探讨对MRI分层低风险直肠癌给予全程新辅助治疗后实施等待观察及器官保留手术的安全性和有效性。方法对北京大学肿瘤医院胃肠肿瘤中心开展的一项前瞻性单臂二期研究进行初步分析。研究对象纳入时间为2016年8月至2019年1月。筛选基线评价为低风险度的中低位直肠癌[初始MRI局部分期为T2或T3a或T3b,且壁外血管侵犯(EMVI)阴性,且环周切缘(CRM)阴性,高、中、低分化腺癌],给予为期1个月的新辅助调强放化疗(IMRT;50.6 Gy/22 f)+同期卡培他滨化疗,在4个月的等待间期,给予4次奥沙利铂+卡培他滨巩固化疗,最终通过临床体检、直肠MRI、内镜评价、血清癌胚抗原等复查手段,明确肿瘤消退的效果,评效为临床完全缓解(cCR)或近cCR(near-cCR)的患者,实施等待观察疗法或器官保留手术。主要研究终点为:器官保留率和括约肌保留率。结果共38例纳入本次初步分析,其中男性24例,女性14例,中位年龄56岁。基线MRI分期:mrT29例(23.7%),mrT3a 14例(36.8%),mrT3b 15例(39.5%);肿瘤分化程度:高、中分化腺癌分别为5例(13.2%)和32例(84.2%)以及黏液腺癌1例(2.6%)。患者治疗前癌胚抗原水平升高1例(2.6%)。调强放疗期间发生3级放射性皮炎1例(2.6%);巩固化疗期间,发生3~4级不良反应18例(47.4%)。全程新辅助治疗结束后评效,cCR率为42.1%(16/38),near-cCR率为23.7%(9/38),非cCR(non-cCR)率为34.2%(13/38)。共20例(52.6%)cCR/near-cCR患者进入等待观察,其中4例出现局部再生。局部切除共4例,包括1例为再生后补救性局部切除。接受根治性切除13例(ypCR 4例):新辅助治疗后直接行低位前切除(LAR)10例,腹会阴联合切除1例,再生后补救性LAR 2例。拒绝手术治疗共4例。中位随访时间23.5(8.5~38.3)月;至末次随访,器官保留率为52.6%(20/38),括约肌保留率为84.2%(32/38);1例局部切除后患者发生肺转移。结论对MRI分层低风险直肠癌实施新辅助放化疗联合巩固�Objective To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer.Methods A prospective single arm phaseⅡtrial developed at Department of Gastrointestinal Cancer,Peking University Cancer Hospital&Institute was preliminarily analyzed.Subjects were enrolled from August 2016 to January 2019.Low-risk rectal cancer with following MRI features were recruited:mid-low tumor,mrT2-3b,MRF(-),EMVI(-),CRM(-),differentiation grade 1-3.Patients received intensity-modulated radiotherapy(IMRT)50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX.Patients with cCR/near-cCR confirmed by physical examination,rectal MRI,endoscopy,and serum CEA were recommended for watch&wait approach or local excision(LE).The main study outcomes were 2-year organ preservation rate(OPR)and sphincter preservation rate(SPR).Results Thirty-eight patients were eligible for analysis,including 24 males and 14 females with median age of 56 years;9 cases of mrT2(23.7%),14 cases of mrT3a(36.8%)and 15 cases of mrT3b(39.5%);5 cases of well differentiated adenocarcinoma(13.2%),32 cases of moderately differentiated adenocarcinoma(84.2%)and 1 case of mucinous adenocarcinoma(2.6%).Carcinoemobryonic antigen(CEA)was elevated before treatment in 1 case.One case(2.6%)of grade 3 radiation dermatitis occurred during IMRT;18 cases(47.4%)occurred grade 3 to 4 adverse events during consolidation chemotherapy.After total neoadjuvant treatment,the cCR and near-cCR rates were 42.1%(16/38)and 23.7%(9/38),respectively,while non-cCR rate was 34.2%(13/38).Twenty patients(20/38,52.6%)of cCR or near-cCR underwent watch&wait approach,with a local regrowth rate of 20%(4/20).Four patients received LE,including one salvage LE.Thirteen patients(4 were ypCR)received radical resection,including 10 cases of initial low anterior resections(LAR),1 cases of initial abdominal perineal resection(APR)and 2 cases of salvage LAR,four patients refused operation.Th

关 键 词：直肠肿瘤 MRI风险分层 全程新辅助治疗 等待观察策略 器官保留 

分 类 号：R735[医药卫生—肿瘤]