放化疗顺序对早期结外鼻型NK/T细胞淋巴瘤患者预后的影响及其个体化应用  

The effects of sequence of radiotherapy and chemotherapy on prognosis of patients with early-stage extranodal NK/T cell lymphoma(nasal type)and its individualized application

作　　者：杨静 杨勇 亓姝楠 吴涛 何侠[3] 张利玲[4] 伍钢[4] 曲宝林[5] 钱立庭 侯晓荣[7] 张福泉[7] 乔学英[8] 汪华 李高峰[10] 朱远 曹建忠[12] 吴君心[13] 朱苏雨 石梅 苏航 张希梅 张会来 黄慧强[18] 张玉晶[18] 宋玉琴 朱军 王颖 李晔雄 Yang Jing;Yang Yong;Qi Shunan;Wu Tao;He Xia;Zhang Liling;Wu Gang;Qu Baolin;Qian Liting;Hou Xiaorong;Zhang Fuquan;Qiao Xueying;Wang Hua;Li Gaofeng;Zhu Yuan;Cao Jianzhong;Wu Junxin;Zhu Suyu;Shi Mei;Su Hang;Zhang Ximei;Zhang Huilai;Huang Huiqiang;Zhang Yujing;Song Yuqin;Zhu Jun;Wang Ying;Li Yexiong(Department of Radiation Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC),Beijing 100021,China;Department of Lymphoma,Affiliated Hospital of Guizhou Medical University,Guizhou Cancer Hospital,Guiyang 550000,China;Department of Radiation Oncology Jiangsu Cancer Hospital,Nanjing 210009,China;Oncology Center of Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430023,China;Department of Radiation Oncology,the First Medical Center of PLA General Hospital,Beijing 100853,China;Department of Radiation Oncology,the Affiliated Provincial Hospital of Anhui Medical University,Hefei 230001,China;Department of Radiation Oncology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC),Beijing 100730,China;Department of Radiation Oncology,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China;Department of Radiation Oncology,Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Radiation Oncology,Beijing Hospital,National Geriatric Medical Center,Beijing 100730,China;Department of Radiation Oncology,Cancer Hospital of the University of Chinese Academy of Sciences,Zhejiang Cancer Hospital,Hangzhou 310022,China;Department of Radiation Oncology,Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Radiation Oncology,Fujian Provincial Cancer Hospital,Fuzhou 350014,China;Department of Radiation Oncology,Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine,Changsha 410013

机构地区：[1]国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院放疗科,北京100021 [2]贵州医科大学附属肿瘤医院贵州省肿瘤医院淋巴瘤科,贵阳550000 [3]江苏省肿瘤医院放疗科,南京210009 [4]华中科技大学同济医学院附属协和医院肿瘤中心,武汉430023 [5]解放军总医院第一医学中心放疗科,北京100853 [6]中国科学技术大学附属第一医院安徽省立医院放疗科,合肥230001 [7]中国医学科学院北京协和医学院北京协和医院放疗科,北京100730 [8]河北医科大学第四医院放疗科,石家庄050011 [9]南昌大学第二附属医院放疗科,南昌330006 [10]北京医院放疗科,北京100730 [11]中国科学院大学附属肿瘤医院浙江省肿瘤医院放疗科,杭州310022 [12]山西医科大学附属肿瘤医院山西省肿瘤医院放疗科,太原030001 [13]福建省肿瘤医院放疗科,福州350014 [14]中南大学湘雅医学院附属肿瘤医院湖南省肿瘤医院放疗科,长沙410013 [15]空军军医大学西京医院放疗科,西安710032 [16]解放军总医院第五医学中心淋巴肿瘤科,北京100071 [17]天津医科大学肿瘤医院放疗科、淋巴瘤科,天津300060 [18]中山大学肿瘤防治中心肿瘤研究所中山大学附属肿瘤医院内科、放疗科,广州510060 [19]北京市肿瘤防治研究所北京大学肿瘤医院淋巴肿瘤科,北京100142 [20]重庆肿瘤医院放疗科,重庆400000

出　　处：《中华医学杂志》2021年第17期1232-1238,共7页National Medical Journal of China

基　　金：国家重大研发计划“精准医学研究”项目(2016YFC0904600);中国医学科学院医学与健康科技创新工程(2016‑I2M‑1‑001)。

摘　　要：目的分析放疗和化疗顺序对早期结外鼻型NK/T细胞淋巴瘤(ENKTCL)患者疗效的影响,为个体化制定放化疗方案提供量化评估方法。方法中国淋巴瘤协作组(CLCG)从全国21家医院收集2000年1月至2019年9月初治的2008例接受放化疗的早期(Ⅰ/Ⅱ期)ENKTCL患者的临床资料,男1417例,女591例,年龄2~83(42±14)岁。根据放化疗顺序将患者分为先放疗组(388例)和先化疗组(1620例)。生存估计采用Kaplan‑Meier法,使用多变量Cox比例风险模型筛选和识别影响预后的独立预测因素。分别构建两种疗法的预后预测模型,并使用该模型预测全部患者的个体化死亡风险,以确定适宜每例患者的放化疗方案。结果先放疗组患者的5年总生存率为74.2%(95%CI:69.6%~79.2%),先化疗组患者的5年总生存率为69.7%(95%CI:67.1%~72.4%);先放疗组患者的5年总生存率虽然数值上高于先化疗组患者,但差异无统计学意义[χ^(2)=2.26,HR=0.84(95%CI:0.68~1.05),P=0.133]。筛选出年龄、性别、美国东部合作肿瘤组(ECOG)评分、乳酸脱氢酶(LDH)、Ann Arbor分期、原发肿瘤侵犯(PTI)等6个变量作为独立预后因素(先化疗组:HR分别为1.01、1.25、2.07、0.77、1.34、1.49,均P<0.05;先放疗组:HR分别为1.02、1.31、1.66、0.78、1.37、1.29,均P>0.05)。全部患者接受先放疗方案的5年期望死亡风险的均值低于接受先化疗方案(26.8%比30.2%,P<0.001)。不同临床特征的患者采用先放疗方案和先化疗方案的预测死亡风险存在个体化差异。结论Ⅰ/Ⅱ期ENKTCL患者采用先放疗方案的期望预后优于采用先化疗方案。根据个体患者的临床特征量化评估放化疗顺序对其死亡风险的差异性影响,有助于临床为该患者制定最佳的放化疗方案。Objective To analyze the effects of the sequence of radiotherapy and chemotherapy on the efficacy of early‑stage extranodal NK/T‑cell lymphoma(nasal type,ENKTCL)patients,and to provide a quantitative evaluation method for individualized radiotherapy and chemotherapy.Methods The Chinese Lymphoma Collaborative Group(CLCG)collected the clinical data of 2008 patients with early‑stageⅠ/ⅡENKTCL who received radiotherapy and chemotherapy from January 2000 to early September 2019 from 21 hospitals across the country,including 1417 males and 591 females,aged 2 to 83(42±14)years.According to the sequence of radiotherapy and chemotherapy,patients were divided into radiotherapy‑first group(388 cases)and chemotherapy‑first group(1620 cases).Survival rate was estimated using Kaplan‑Meier method,and multivariate Cox proportional risk model was used to screen and identify independent prognostic factors.The prognostic prediction models of the two therapies were constructed separately,and the models were used to predict the individualized mortality risk of all patients to determine the appropriate radiotherapy and chemotherapy regimen for each patient.Results The 5‑year overall survival rate was 74.2%(95%CI:69.6%-79.2%)in the radiotherapy‑first group and 69.7%(95%CI:67.1%-72.4%)in the chemotherapy‑first group.Although the 5‑year overall survival rate of patients in the radiotherapy‑first group was numerically higher than that of the chemotherapy‑first group,the difference was not statistically significant(χ^(2)=2.26,HR=0.84(95%CI:0.68-1.05),P=0.133).Six variables including age,gender,ECOG score,LDH,Ann Arbor staging,and PTI(primary tumor invasion)were screened out as independent prognostic factors(the chemotherapy‑first group:HR were 1.01,1.25,2.07,0.77,1.34,1.49,respectively,all P<0.05;radiotherapy‑first group:HR were 1.02,1.31,1.66,0.78,1.37,1.29,all P>0.05).The mean 5‑year predicted mortality risk for all patients receiving radiotherapy‑first regimen was lower than those receiving chemother

关 键 词：淋巴瘤 结外NK‑T细胞 放射疗法 化学疗法 个体化 

分 类 号：R733.1[医药卫生—肿瘤]