局晚期下咽癌诱导免疫化疗后客观缓解率的前瞻性Ⅱ期临床研究  

Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma:a prospective phaseⅡstudy

作　　者：龚洪立 田姝 丁浩 陶磊 王丽 王杰 王天 张明 施勇 徐成志 吴春萍 王胜资 周梁 Gong Hongli;Tian Shu;Ding Hao;Tao Lei;Wang Li;Wang Jie;Wang Tian;Zhang Ming;Shi Yong;Xu Chengzhi;Wu Chunping;Wang Shengzi;Zhou Liang(Department of Otorhinolaryngology Head and Neck Surgery,Eye&ENT Hospital,Fudan University,Shanghai 200031,China;Department of Radiation Oncology,Eye&ENT Hospital,Fudan University,Shanghai 200031,China)

机构地区：[1]复旦大学附属眼耳鼻喉科医院耳鼻咽喉头颈外科,上海200031 [2]复旦大学附属眼耳鼻喉科医院放疗科,上海200031

出　　处：《中华耳鼻咽喉头颈外科杂志》2024年第4期350-356,共7页Chinese Journal of Otorhinolaryngology Head and Neck Surgery

基　　金：国家自然科学基金(81502343,81972529);上海市申康医院发展中心(SHDC2020CR6011);上海市科学技术委员会(16411950100,21Y11900100,shslczdzk00801);北京白求恩公益基金(2021-YJ-088-J)。

摘　　要：目的评价诱导免疫化疗治疗局晚期可手术切除的不能保喉的下咽鳞状细胞癌的客观缓解率(objective response rate,ORR),并探讨影响ORR的临床因素。方法本研究为单中心、前瞻性、单臂Ⅱ期临床研究,入组时间为2021年5月至2023年4月就诊于复旦大学附属眼耳鼻喉科医院的患者,主要研究目的是评价诱导免疫化疗[卡瑞利珠单抗+TPF(多西他赛+顺铂+卡培他滨)]治疗局晚期可手术切除、不能保喉的T3-4N0-3M0期下咽癌患者的ORR,包括完全缓解(CR)和部分缓解(PR)。诱导治疗后采用肿瘤体积评价ORR,同时实体瘤疗效评价标准(RECIST)1.1作为参考,计算治疗前、后原发灶肿瘤体积的退缩率,如肿瘤体积完全缓解或退缩PR>70%(PR>70%组),采用放疗联合免疫治疗,如果≤70%(PR≤70%组),则手术治疗。数据录入和分析采用SPSS 23.0软件建库分析。结果研究入组51例患者,均为男性,年龄35~69岁,均接受3程诱导免疫化疗,PR>70%组患者42例,PR≤70%组9例,ORR为82.4%,达到预期主要研究目的。PR≤70%组的T分期较PR>70%组更晚,原发灶肿瘤体积在治疗前和治疗后均较PR>70%组更大,而肿瘤体积退缩率较低,差异均有统计学意义(P值均<0.05)。判断诱导免疫化疗肿瘤退缩的ORR最佳治疗前肿瘤体积截断值是39 cm^(3),T分期[OR(95%CI)为12.7(1.4~112.5),P=0.022]和原发灶肿瘤体积[OR(95%CI)为7.1(1.4~36.8),P=0.018]是影响ORR的两个因素。结论诱导免疫化疗方案短期内具有良好的临床疗效,有潜力应用于今后的局晚期头颈癌的临床治疗。Objective To evaluate the objective response rate(ORR)of induction chemoimmunotherapy with camrelizumab plus TPF(docetaxel,cisplatin,and capecitabine)for locally advanced hypopharyngeal squamous cell carcinoma(LA HSCC)and potential predictive factors for ORR.Methods A single-center,prospective,phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine)for LA HSCC between May 21,2021 and April 15,2023,patients admitted to the Eye&ENT Hospital affiliated with Fudan University.The primary endpoint was ORR,and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles:camrelizumab 200 mg day 1,docetaxel 75 mg/m^(2) day 1,cisplatin 25 mg/m^(2) days 1-3,and capecitabine 800 mg/m^(2) days 1-14.Patients were assigned to radioimmunotherapy when they had complete response or partial response(PR)>70%(Group A),or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70%(Group B),and the responses were defined by using tumor volume evaluation system.Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1.Use SPSS 23.0 software was used to analyze the data.Results A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles,and all were males,aged 35-69 years old.After three cycles of induction immunochemotherapy,42(82.4%)patients existed in Group A(complete response or PR>70%)and 9 patients(17.6%)in Group B(PR≤70%),the ORR was 82.4%.The primary endpoint achieved expected main research objectives.Compared to the patients of Group A,the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy,and also had the less regression of tumor volume after induced immunochemotherapy(all P<0.05).The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm^(3).The T stage(OR=12.71,95%CI:1.4-112.5,P=0.022)

关 键 词：下咽肿瘤 诱导化疗 免疫治疗 客观缓解率 

分 类 号：R739.63[医药卫生—肿瘤]