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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes Hematology Hospital SuzhouChina Department of Hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(os)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year os of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve os in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang ma Jing-Ping Yun Judy Wai Ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;maID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;os,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;Tma,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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TKIs联合化疗治疗成人Ph阳性急性淋巴细胞白血病的疗效及预后分析

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中国肿瘤临床 2024年第6期51卷 287-292页

作者：马小楠郑波宁夏医科大学总医院血液内科银川市750004 宁夏医科大学临床医学院

目的:探讨成人费城染色体阳性急性淋巴细胞白血病(Philadelphia chromosome-positive acute lymphoblastic leukemia,Ph+ALL)患者化疗及酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)联合化疗作为首次诱导治疗的疗效及预后。方法:回顾性分析2012年1月至2023年10月就诊于宁夏医科大学总医院的60例成人Ph+ALL患者临床特点、生物学特征及完全缓解情况,分析其疗效及预后。结果:首次诱导治疗后达到完全缓解率(complete response,CR)的患者有43例,占71.67%(43/60),其中单纯化疗组7例,占41.18%(7/17),TKI+化疗组CR率为36例,占83.72%(36/43),且两组差异具有统计学意义(P=0.003)。单纯化疗组患者的2年总生存(overall survival,os)率为28.2%,TKI联合化疗组患者的2年os率为56%,差异具有统计学意义(P=0.041)。移植组与非移植组患者2年os率76.9%vs. 51.9%,5年os率56.1%vs. 19.4%,(P=0.003);2年无进展生存(progression-free survival,PFS)率38.5%vs. 12.1%(P=0.018),二者差异均具有统计学意义。单因素预后分析示,是否选择TKI、初次诱导治疗后是否获得CR和是否骨髓移植对os预后差异均具有统计学意义(Pos的独立预后因素。结论:Ph+ALL诱导治疗方案中,TKI+化疗诱导治疗方案能够实现早缓解,高缓解率,总生存期方面优于单纯化疗。缓解后进行骨髓造血干细胞移植治疗Ph+ALL预后良好。

关键词：急性淋巴细胞白血病费城染色体阳性酪氨酸激酶抑制剂化疗

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口腔鳞状细胞癌列线图预后模型建立与评估

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实用口腔医学杂志 2024年第4期40卷 529-536页

作者：马武陈林林南昌大学附属口腔医院口腔疾病江西省重点实验室江西省口腔疾病临床医学研究中心330006

目的:探讨口腔鳞状细胞癌(osCC)患者预后相关因素,建立列图预测模型,对osCC患者总生存时间(os)及无病生存时间(DFS)进行评估。方法:回顾性分析361例口腔鳞癌患者的临床病理资料,采用Log-rank检验及COX模型单因素及多因素分析口腔鳞癌os... 详细信息

目的:探讨口腔鳞状细胞癌(osCC)患者预后相关因素,建立列图预测模型,对osCC患者总生存时间(os)及无病生存时间(DFS)进行评估。方法:回顾性分析361例口腔鳞癌患者的临床病理资料,采用Log-rank检验及COX模型单因素及多因素分析口腔鳞癌os及DFS的危险因素,并以此建立列线图模型。采用一致性指数(C指数)、受试者工作特征曲线(ROC)及校准曲线对列线图模型进行验证和评价。结果:共随访到277例患者结局,随访率76.73%。COX单因素及多因素分析结果显示,年龄、神经周围浸润、肿瘤分化程度及N分期均为osCC患者os的独立危险因素,年龄、神经周围浸润、肿瘤分化程度及临床分期均为osCC患者DFS的独立危险因素(PosCC患者术后os和DFS的C指数分别为0.741和0.763,受试者工作特征曲线及校准曲线均表明预后模型与实际观测结果拟合性较好。结论:基于年龄、神经周围浸润、肿瘤分化程度、N分期和临床分期构建的osCC术后os、DFS列线图模型具有良好的预测能力及精准度,有助于临床医师准确评估患者预后,指导临床个体化治疗。

关键词：口腔鳞状细胞癌列线图预后模型

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核热火箭发动机研制进展与关键技术

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火箭推进 2024年第4期50卷 1-13页

作者：马晓秋解家春北京航天动力研究所低温液体推进技术实验室北京100076 中国原子能科学研究院北京102413

介绍了核热火箭发动机基本原理,回顾和分析了美、俄(苏联)核热火箭发动机的研制历程。美国在早期核热火箭发动机的研制过程中主要采用整机试验模式进行研究,Rover/NERVA期间先后建立了20余个反应堆,获得了大量的试验数据,这些数据至今... 详细信息

介绍了核热火箭发动机基本原理,回顾和分析了美、俄(苏联)核热火箭发动机的研制历程。美国在早期核热火箭发动机的研制过程中主要采用整机试验模式进行研究,Rover/NERVA期间先后建立了20余个反应堆,获得了大量的试验数据,这些数据至今仍在美国核热火箭发动机的研究中发挥着重要作用。后续在SNTP计划中以提高反应堆性能为目标进行了颗粒床反应堆(PBR)研究。在NCPS计划中提出了经济可承受的思路,并采用电加热非核模拟方式开展燃料元件的筛选研究,降低了成本和危险性。在任务需求方面,围绕载人登火和地月经济圈活动,提出了dra5.0载人火星计划以及天龙座(draCO)计划。俄罗斯(苏联)与美国基本同时开展了核热发动机研究,其技术路线主要以反应堆燃料元件技术为主,研制出扭转条状耐高温的多元碳化物燃料元件,参数水平居于世界领先。通过总结美俄核热火箭发动机的研制趋势,对核热火箭发动机反应堆关键技术进行了分析,并对我国未来开展核热火箭发动机的研究提出了发展建议。

关键词：核热火箭发动机比冲反应堆关键技术燃料元件

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qGW11a/osCAT8,encoding an amino acid permease,negatively regulates grain size and weight in rice

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The Crop Journal 2024年第4期12卷 1150-1158页

作者： Peng Gao Feifan Chen Haitang Liu Shijun Fan Jierui Zeng Xue Diao Yang Liu Wencheng Song Shifu Wang Jing Li Xiaobo Zhu Bin Tu Weilan Chen Ting Li Yuping Wang Bingtian ma Shigui Li Hua Yuan Peng Qin State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Rice Research InstituteSichuan Agricultural UniversityChengdu 611130SichuanChina

Grain size is a key factor influencing grain weight in *** this study,a chromosome segment substitution line(CSSL9-17)was identified,that exhibits a significant reduction in both grain size and weight compared to its donor parent *** investigation identified two quantitative trait loci(QTL)on chromosome 11,designated qGW11a and qGW11b,which contribute to 1000-grain weight with an additive ***_os11g05690,encoding the amino acid permease osCAT8,is the target gene of *** of osCAT8 resulted in decreased grain weight,while osCAT8 knockout mutants exhibited increased grain *** 287-bp located within the osCAT8 promoter region of 93-11 negatively regulates its activity,which is subsequently correlated with an increase in grain size and *** results suggest that osCAT8 functions as a negative regulator of grain size and grain weight in rice.

关键词： Rice Grain size Grain weight QTL osCAT8

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长链非编码RNA HEIH在急性髓系白血病患者中的表达及临床意义

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中国实验血液学杂志 2024年第4期32卷 1011-1017页

作者：马悦李佳佳蚌埠医学院第一附属医院血液科安徽蚌埠233000

目的:探讨长链非编码RNA HEIH在急性髓系白血病患者中的表达情况及临床意义。方法:2019年1月至2020年12月就诊于蚌埠医学院附属第一医院的50例初诊AML住院患者(M3除外)纳入研究,以30例血液系统非恶性肿瘤患者作为对照。检测所有患者lnc ... 详细信息

目的:探讨长链非编码RNA HEIH在急性髓系白血病患者中的表达情况及临床意义。方法:2019年1月至2020年12月就诊于蚌埠医学院附属第一医院的50例初诊AML住院患者(M3除外)纳入研究,以30例血液系统非恶性肿瘤患者作为对照。检测所有患者lnc RNA HEIH的相对表达量,分析AML患者的临床特征、基因突变情况、FAB分型、疗效、预后及总生存期(os)等与lnc RNA HEIH表达水平的相关性。结果:AML患者的lnc RNA HEIH相对表达水平明显高于血液系统非恶性肿瘤患者(P<0.01)。在AML患者中,高白细胞计数、CEBPA和FLT3基因突变、疗效差、预后不良的患者往往有较高的lnc RNA HEIH表达水平,且lnc RNA HEIH高表达的患者生存期较短。结论:lncRNA HEIH在AML患者中显示出独特的分子生物学意义,或许可为AML的诊断、监测及靶向治疗提供新方案。

关键词：急性髓系白血病 lncRNA HEIH 临床特征疗效预后

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Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study

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Chinese Journal of Integrative Medicine 2024年第6期30卷 489-498页

作者： CAO Ni-da ZHU Xiao-hong ma Fang-qi XU Yan DONG Jia-huan QIN Meng-meng LIU Tian-shu ZHU Chun-chao GUO Wei-jian DING Hong-hua GUO Yuan-biao LIU Li-kun SONG Jin-jie WU Ji-ping CHENG Yue-lei ZENG Lin ZHAO Ai-guang Oncology Department I Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghai200032China Oncology Department Zhongshan HospitalFudan UniversityShanghai200032China Gastrointestinal Surgery Department Renji HospitalShanghai Jiaotong University School of MedicineShanghai200127China Oncology Department Fudan University Shanghai Cancer CenterShanghai200032China Oncology Department Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080China Traditional Chinese Medicine Department Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai200025China Oncology Department Shanxi Traditional Chinese Medicine HospitalTaiyuan030012China Oncology Department Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing102445China Oncology Department Yunnan Province Hospital of Traditional Chinese MedicineKunming650021China Oncology Department Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai201203China Shanghai NewCore Biotechnology Co. Ltd.Shanghai200240China

Objective To describe the treatment patterns and survival status of advanced gastric cancer(AGC)in China in the past two decades,and objectively evaluate the impact of standardized Chinese medicine(CM)treatment on the survival of AGC *** This multicenter registry designed and propensity score analysis study described the diagnosis characteristics,treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1,2000 and July 31,*** survival(os)was evaluated between non-CM cohort(standard medical treatment)and CM cohort(integrated standard CM treatment≥3 months).Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were performed to adjust any difference in average outcomes for *** A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were *** them,1,607 received systemic chemotherapy,215(10.74%)accepted molecular targeted therapy,44(2.2%)received checkpoint inhibitor therapy,and 769(38.43%)received ***-drug regimen was the main choice for first-line treatment,with fluoropyrimidine plus platinum as the most common regimen(530 cases,60.09%).While 45.71%(16 cases)of patients with HER2 amplification received trastuzumab in *** application of apatinib increased(33.33%)in *** application of checkpoint inhibitors has increased since *** analysis showed that Lauren mixed type(P=0.017),cycles of first-line treatment>6(P=0.000),CM(P=0.000),palliative gastrectomy(P=0.000),trastuzumab(P=0.011),and apatinib(P=0.008)were independent prognostic factors for the os of *** PSM and IPTW,the median os of CM cohort and non-CM cohort was 18.17 and 12.45 months,respectively(Pmain first-line *** CM treatment was an independent

关键词： advancedgastriccancer real-world study treatment pattern survival analysis Chinese medicine

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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen Xing Li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(os)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median os was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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胶质母细胞瘤肿瘤电场治疗的疗效观察

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中华神经外科杂志 2024年第6期40卷 564-568页

作者：郭晓鹏邢浩王裕马文斌中国医学科学院北京协和医学院北京协和医院神经外科北京100730

目的探讨胶质母细胞瘤(GBM)肿瘤电场治疗(TTFields)的临床疗效及其不良事件(AE)发生情况.方法回顾性分析中国医学科学院北京协和医学院北京协和医院神经外科2019年9月至2023年12月采用TTFields治疗的12例GBM患者的临床资料.其中8例新诊... 详细信息

目的探讨胶质母细胞瘤(GBM)肿瘤电场治疗(TTFields)的临床疗效及其不良事件(AE)发生情况.方法回顾性分析中国医学科学院北京协和医学院北京协和医院神经外科2019年9月至2023年12月采用TTFields治疗的12例GBM患者的临床资料.其中8例新诊断的GBM患者在术后2~6周开始进行替莫唑胺(TMZ)同步放化疗,续贯TMZ辅助化疗(标准Stupp方案),同时应用TTFields;4例复发性GBM患者术后2~6周开始应用TTFields,其中3例同时应用了贝伐单抗靶向治疗.所有患者每2~4个月随访1次,评估患者的生存情况及与TTFields相关的AE,采用不良事件通用术语评级标准(CTCAE)评估AE的严重程度.结果12例患者应用TTFields的中位总时长为6.5个月(1~47个月),每日治疗的中位时长为23.0 h(8.0~23.5 h).9例患者发生与TTFields相关的AE,其中6例为皮炎,3例为皮肤发热感;CTCAE 1级5例、2级3例、3级1例.12例患者的中位随访时间为14个月(7~51个月),其中8例患者的总随访时间≥12个月.至末次随访,10例生存,2例分别于术后15、33个月死亡.8例患者随访到的无进展生存期(PFS)为2~26个月,其中4例患者的PFS≥12个月.结论对于新诊断及复发性GBM患者,规律及长期应用TTFields仅造成轻、中度的局部皮肤AE,可能会使患者生存获益.

关键词：胶质母细胞瘤治疗结果肿瘤电场治疗不良事件

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