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SHr-A1811(antibody-drug conjugate)in advanced HEr2.mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2.study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming li Zhengbo {2. Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin liang Sheng Hu min peng Yan Yu Yan Wang Zicong Jiao Kaijing zhao Ke {2. You li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China department of Thoracic Oncology Zhejiang Cancer HospitalHangzhou 310000China department of Lung&Gastrointestinal Oncology Hunan Cancer HospitalChangsha 410031China Thoracic Oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China department of Thoracic Oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China department of Medical Oncology Hubei Cancer HospitalWuhan 43000China department of Oncology Renmin Hospital of Wuhan UniversityWuhan 430200China department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China department of Medical Oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2.study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHr-A1811 in pretreated HEr2.altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHr-A1811 intravenously at doses of 3.2.to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HEr2.mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 2.(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2.2.,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 2..0-57.9),and a disease control rate of 95.3%(95%Cl 84.2.99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHr-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HEr2.mutantNSCLC.

关键词： SHr HEr2 doses

Expert consensus on pediatric orthodontic therapies of malocclusions in children

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International Journal of Oral Science 2024年第2期16卷 186-196页

作者： Chenchen Zhou peipei Duan Hong He Jinlin song {2. Hu Yuehua liu Yan liu Jie guo Fang Jin Yang Cao lingyong Jiang Qingsong Ye {2. Zhu Beizhan Jiang Wenhua ruan Xiao Yuan Huang li rui Zou Yulou Tian li Gao rui Shu Jianwei Chen renkai liu Shujuan Zou Xiaobing li State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical research Center for Oral Diseases&department of pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical research Center for Oral Diseases&department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral and Maxillofacial reconstruction and regeneration&Key Laboratory of Oral Biomedicine ministry of Education&Hubei Key Laboratory of Stomatology&department of Orthodontics&Center for Dentofacial Development and Sleep Medicine School and Hospital of StomatologyWuhan UniversityWuhanChina Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences&Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education Stomatological Hospital of Chongqing Medical UniversityChongqing Medical University&College of StomatologyChongqing Medical UniversityChongqingChina department of Orthodontics Hospital of StomatologyJilin UniversityChangchunChina department of Orthodontic&Oral Biomedical Engineering Laboratory Shanghai Stomatological HospitalFudan UniversityShanghaiChina department of Orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina department of Orthodontics School and Hospital of StomatologyCollege of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~2.0 million children in *** its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these *** intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the *** orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition *** an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social *** consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early *** elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

关键词： permanent stated children

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

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World Journal of pediatrics 2024年第9期20卷 901-914页

作者： Ying-Shuo Wang Yun-lian Zhou Guan-Nan Bai Shu-Xian li Dan Xu li-Na Chen Xing Chen Xiao-Yan Dong Hong-min Fu Zhou Fu Chuang-li Hao Jian-guo Hong En-Mei liu Han-min liu Xiao-Xia Lu Zheng-Xiu Luo Lan-Fang Tang Man Tian Yong Yin Xiao-Bo Zhang Jian-Hua Zhang Hai-lin Zhang De-Yu zhao Shun-Ying zhao guo-Hong Zhu Ying-Xue Zou Quan Lu Yuan-Yuan Zhang Zhi-min Chen department of pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Child Health Care Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of pediatric pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China department of pediatrics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China department of pulmonology Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China department of pulmonary and Critical Care Medicine Kunming Children’s HospitalKunming 650034China department of respiratory Medicine Children’s Hospital of Chongqing Medical UniversityChongqing 400014China department of pulmonology Children’s Hospital of Soochow UniversitySuzhou 215003China department of pediatrics Shanghai General Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200080China department of respiratory Medicine Wuhan Children’s HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430015China department of respiratory Medicine Children’s Hospital of Nanjing Medical UniversityNanjing 210008China department of respiratory Medicine Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China department of respiratory Medicine Children’s Hospital of Fudan UniversityShanghai 201102China department of pediatric pulmonology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 201102China department of pediatric respiratory Medicine The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027China National Clinical research Center for respiratory Diseases Beijing Children’s HospitalCapital Medical UniversityBeijing 100045China Departmen

Background Mycoplasma pneumoniae(***)is a significant contributor to community-acquired pneumonia among *** 1968,when a strain of *** resistant to macrolide antibiotics was initially reported in Japan,macrolide-resistant ***(MrMp)has been documented in many countries worldwide,with varying incidence *** infections lead to a poor response to macrolide antibiotics,frequently resulting in prolonged fever,extended antibiotic treatment,increased hospitalization,intensive care unit admissions,and a significantly higher proportion of patients receiving glucocorticoids or second-line *** 2.00,the global incidence of MrMp has gradually increased,especially in East Asia,which has posed a serious challenge to the treatment of *** infections in children and attracted widespread attention from ***,there is still no global consensus on the diagnosis and treatment of MrMp in *** We organized 2. Chinese experts majoring in pediatric pulmonology and epidemiology to write the world’s first consensus on the diagnosis and treatment of pediatric MrMp pneumonia,based on evidence *** evidence searches and reviews were conducted using electronic databases,including pubMed,Embase,Web of Science,CNKI,Medline,and the Cochrane *** used variations in terms for“macrolide-resistant”,“Mycoplasma pneumoniae”,“Mp”,“***”,“pneumonia”,“MrMp”,“lower respiratory tract infection”,“Mycoplasma pneumoniae infection”,“children”,and“pediatric”.results Epidemiology,pathogenesis,clinical manifestations,early identification,laboratory examination,principles of antibiotic use,application of glucocorticoids and intravenous immunoglobulin,and precautions for bronchoscopy are *** and rapid identification of gene mutations associated with MrMp is now available by polymerase chain reaction and fluorescent probe techniques in respiratory *** the resistance rate to mac

关键词： Child Macrolide-resistant Mycoplasma pneumoniae recommendation Diagnosis Treatment

The Design of GECAM Scientific Ground Segment

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research in Astronomy and Astrophysics 2024年第10期24卷 1-10页

作者： Shijie Zheng liming {2. Xiang Ma ping Wang rui Qiao Yue Huang Xiaoyun zhao Hongmei Zhang Xiaobo li mingyu Ge Gang Chen Gongxing Sun Wenxi peng Ce Cai Wei Chen Yanqi Du Dongya guo Bing li Chaoyang li Jianhui li Qingxin li Jing liang Jiacong liu Ge Ou Dongli Shi Jingyan Shi Xinying {2. Jin Wang Wenshuai Wang Hong Wu Shuo Xiao Wangchen Xue min Yao Jianying Ye Kai Zhang peng Zhang Xiaolu Zhang Yanqiu Zhang guoying zhao Shiyi zhao Chao Zheng Shaolin Xiong Key Laboratory of particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Shanghai Astronomical Observatory Chinese Academy of SciencesShanghai 200030China Southwest Jiaotong University Chengdu 611756China Xiangtan University Changsha 411105China Qufu Normal University Qufu 273165China

The Gravitational wave burst high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)is a dedicated mission for monitoring high-energy *** we report the design of the GECAM Scientific Ground Segment(GSGS)in terms of the scientific requirements,including the architecture,the external interfaces,the main function,and *** from the analysis and verification results during the commissioning phase,the GSGS functions well and is able to monitor the status of the payloads,adjust the parameters,develop the scientific observation plans,generate the scientific data products,analyze the data,***,the on-orbit operation and scientific researches of GECAM are guaranteed.

关键词： gravitational waves gamma-rays:general telescopes

Genomic characterization and risk stratification of esophageal squamous dysplasia

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Medical review 2024年第3期4卷 244-256页

作者： Qingjie min min Zhang Dongmei {2.n Weimin Zhang Xianfeng {2. {2.anmei zhao Huajing Teng Tao He Wei Sun Jiawen Fan Xiying Yu Jie Chen Jinting {2. Xiaohan Gao Bin Dong rui {2.u Xuefeng {2.u Yongmei song Yongping Cui Shih-Hsin Lu ruiqiang {2. mingzhou guo Yan Wang Qimin Zhan Key Laboratory of Carcinogenesis and Translational research(ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijingChina Novogene Co.Ltd BeijingChina department of pathology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital&InstituteBeijingChina department of Gastroenterology Daping HospitalArmy Medical University(Third Military Medical University)ChongqingChina research Center The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiChina department of radiation Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital&InstituteBeijingChina department of Gastroenterology&Hepatology Chinese PLA General HospitalBeijingChina department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State Key Laboratory of Molecular Oncology Cancer Institute and Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Carcinogenesis and Translational research(ministry of Education/Beijing) Central LaboratoryPeking University Cancer Hospital&InstituteBeijingChina Institute of Cancer Stem Cell Dalian Medical UniversityDalianLiaoningChina Shenzhen peking University-The Hong Kong University of Science and Technology(pKU-HKUST)Medical Center Peking University Shenzhen HospitalShenzhenGuangdongChina

Objectives:The majority of esophageal squamous dysplasia(ESD)patients progress slowly,while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper ***,the molecular mechanisms underlying these clinical observations are still largely ***:By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma(ESCC)patients,we demonstrated lower somatic mutation and copy number alteration(CNA)burden in ESD compared with ***:Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD ***,we revealed that mir-42.2.promoted ESD progression and could serve as a non-invasive diagnostic marker for ***:These findings largely expanded our understanding of ESD genetics and tumorigenesis,which possessed promising significance for improving early diagnosis,reducing overtreatment,and identifying high-risk ESD patients.

关键词： esophageal squamous dysplasia genomic alteration ACSM5 early diagnosis mir-42.2

Observation of maximal intrinsic chirality empowered by dual quasi-bound states in the continuum in a planar metasurface

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photonics research 2024年第2期12卷 244-252页

作者： XIN QI JIAJU WU FENG WU song zhao CHAO WU YUEYANG {2. {2.A rEN YUFEI WANG HAITAO JIANG YUNHUI li ZHIWEI guo YApING YANG WANHUA ZHENG HONG CHEN YONG SUN MOE Key Laboratory of Advanced Micro-Structured Materials School of Physics Science and EngineeringTongji UniversityShanghai 200092China School of Optoelectronic Engineering Guangdong Polytechnic Normal UniversityGuangzhou 510665China l3 Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology School of Physics Science and EngineeringTongji UniversityShanghai 200092China department of Electrical Engineering Tongji UniversityShanghai 201804China State Key Laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China

Metasurfaces with spin-selective transmission play an increasingly critical role in realizing optical chiral responses,especially for strong intrinsic chirality,which is limited to complex three-dimensional *** this paper,we propose a planar metasurface capable of generating maximal intrinsic chirality and achieving dual-band spinselective transmission utilizing dual quasi-bound states in the continuum(quasi-BICs)caused by the structural symmetry ***,the value of circular dichroism(CD)and the transmittance of two kinds of circular polarization states can be arbitrarily controlled by tuning the asymmetry *** CD approaching unity with the maximum transmittance up to 0.95 is experimentally achieved in the dual ***,assisted by chiral BICs,the application in polarization multiplexed near-field image display is also *** work provides a new avenue to flexibly control intrinsic chirality in planar structure and offers an alternative strategy to develop chiral sensing,multiband spin-selective transmission,and high-performance circularly polarized wave *** basic principle and design method of our experiments in the microwave regime can be extended to other bands,such as the terahertz and infrared wavelengths.

关键词： planar intrinsic quasi

Mobius Isoparametric Hypersurfaces in S^(n+1) with Two Distinct principal Curvatures

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Acta Mathematica Sinica,English Series 2002年第3期18卷 437-446页

作者： Hai Zhong li department of {2., Tsinghua University. Beijing 100084. p. r. china Hui li liU department of {2., Northeastern University. Shenyang 110000. p. r. china Chang ping WANG Key Laboratory of pure and Applied {2., School of Mathematical Sciences. peking University, Beijing 100871, p. r. china {12. song zhao department of {2., sichuan University, chengdu 610064. p. r. china department of mathematics Tsinghua University Beijing P. R. China department of mathematics Northeastern University Shenyang P. R. China Key Laboratory of pure and Applied mathematics School of Mathematical Sciences Peking University Beijing P. R. China department of mathematics Sichuan University Chengdu P. R. China

A hypersurface x: M→S^(n+1) without umbilic point is called a Mbius isoparametric hypersurface if its Mbius form Φ=-ρ^(-2.∑_i(ei(H)+∑_j(h_(ij)-Hδ_(ij))e_j(logρ))θ_i vanishes and its Mbius shape operator S=ρ^(-1)(S-Hid) has constant eigenvalues. Here {e_i} is a local orthonormal basis for I=dx·dx with dual basis {θ_i}, II=∑_(ij)h_(ij)θ_iθ_J is the second fundamental form, H=1/n∑_i h_(ij), ρ~2.n/(n-1)(‖II‖~2.nH^2. and S is the shape operator of x. It is clear that any conformal image of a (Euclidean) isoparametric hypersurface in S^(n+1) is a Mbius isoparametric hypersurface, but the converse is not true. In this paper we classify all Mbius isoparametric hypersurfaces in S^(n+1) with two distinct principal curvatures up to Mbius transformations. By using a theorem of Thorbergsson [1] we also show that the number of distinct principal curvatures of a compact Mbius isoparametric hypersurface embedded in S^(n+1) can take only the values 2. 3, 4, 6.

关键词： Mobius geometry Isoparametric hypersurface principal curvature

A Localization Method of High Energy Transients for All-sky Gamma-ray Monitor

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research in Astronomy and Astrophysics 2024年第10期24卷 25-35页

作者： Yi zhao Wangchen Xue Shaolin Xiong Qi Luo Yuanhao Wang Jiacong liu Heng Yu Xiaoyun zhao Yue Huang Jinyuan liao Jianchao Sun Xiaobo li Qibin Yi Ce Cai Shuo Xiao Shenglun Xie Chao Zheng Yanqiu Zhang Chenwei Wang Wenjun Tan Zhiwei guo Chaoyang li Zhenghua An Gang Chen Yanqi Du min Gao Ke Gong Dongya guo Jiang He Jianjian He Bing li Gang li Xinqiao li Jing liang Xiaohua liang Yaqing liu Xiang Ma rui Qiao liming song Xinying song Xilei Sun Jin Wang ping Wang Xiangyang Wen Hong Wu Yanbing Xu Sheng Yang Dali Zhang Fan Zhang Hongmei Zhang peng Zhang Shu Zhang Zhen Zhang Shijie Zheng Keke Zhang Xingbo Han Haiyan Wu Hu Tai Hao Geng Gaopeng Lu Wei Xu Fanchao Lyu Hongbo Zhang Fangjun Lu Shuangnan Zhang department of Astronomy Beijing Normal UniversityBeijing 100875China Key Laboratory of particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China School of physics and Optoelectronics Xiangtan UniversityXiangtan 411105China College of physics Hebei Normal UniversityShijiazhuang 050024China Guizhou provincial Key Laboratory of radio Astronomy and Data processing Guizhou Normal UniversityGuiyang 550001China School of physics and Electronic Science Guizhou Normal UniversityGuiyang 550001China Institute of Astrophysics Central China Normal UniversityWuhan 430079China College of physics Sciences Technology Hebei UniversityBaoding 071002China physics and Space Science College China West Normal UniversityNanchong 637002China School of Computing and Artificial Intelligence Southwest Jiaotong UniversityChengdu 611756China College of Electronic and information Engineering Tongji UniversityShanghai 201804China Innovation Academy for Microsatellites of Chinese Academy of Sciences Shanghai 201304China National Space Science Center Chinese Academy of SciencesBeijing 100190China School of Earth and Space Sciences University of Science and Technology of ChinaHefei 230026China Electronic Information School Wuhan UniversityWuhan 430072China Key Laboratory of Transportation Meteorology of china Meteorological Administration Nanjing Joint Institute for Atmospheric SciencesNanjing 210000China Key Laboratory of Middle Atmosphere and Global Environment Observation Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China

Fast and reliable localization of high-energy transients is crucial for characterizing the burst properties and guiding the follow-up *** based on the relative counts of different detectors has been widely used for all-sky gamma-ray *** are two major methods for this count distribution localization:χ^(2.minimization method and the Bayesian *** we propose a modified Bayesian method that could take advantage of both the accuracy of the Bayesian method and the simplicity of the χ^(2.*** comprehensive simulations,we find that our Bayesian method with poisson likelihood is generally more applicable for various bursts than the χ^(2.method,especially for weak *** further proposed a location-spectrum iteration approach based on the Bayesian inference,which could alleviate the problems caused by the spectral difference between the burst and location *** method is very suitable for scenarios with limited computation resources or timesensitive applications,such as in-flight localization software,and low-latency localization for rapidly follow-up observations.

关键词： methods:data analysis methods:analytical (stars:)gamma-ray burst:general

Updated overall survival and circulating tumor DNA analysis of ensartinib for crizotinib-refractory ALK-positive NSCLC from a phase II study

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Cancer Communications 2024年第4期44卷 455-468页

作者： Jing Zheng Tao Wang Yunpeng Yang Jie Huang Jifeng Feng Wu Zhuang Jianhua Chen Jun zhao Wei Zhong Yanqiu zhao Yiping Zhang Yong {2. Yi Hu Zhuang Yu Youling Gong Yuan Chen Feng Ye Shucai Zhang Lejie Cao Yun Fan Gang Wu Yubiao guo Chengzhi Zhou Kewei Ma Jian Fang Weineng Feng Yunpeng liu Zhendong Zheng Gaofeng li Huijie Wang Shundong Cang Ning Wu Wei {2. Xiaoqing liu Shijun zhao lieming Ding Giovanni Selvaggi Yang Wang Shanshan Xiao Qian Wang Zhilin Shen Jianya Zhou Jianying Zhou li Zhang department of respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityZhejiang Provincial Clinical Research Center for Respiratory DiseaseHangzhouZhejiangP.R.China Hangzhou repugene Technology Co. LtdHangzhouZhejiangP.R.China department of Medical Oncology Sun Yat-sen University Cancer Cen-terState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China department of Medical Oncology Jiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsuP.R.China department of Thoracic Oncology Fujian Provincial Cancer HospitalFujian Medical University Cancer HospitalFuzhouFujianP.R.China department of Medical Oncology-Chest Hunan Cancer HospitalChangshaHunanP.R.China department of Thoracic Oncology Beijing Cancer HospitalBeijingP.R.China department of pulmonary Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijingP.R.China respiratory department of Internal Medicine Henan Provincial Can-cer HospitalAffiliated Cancer Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Thoracic Medical Oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China Division of respiratory Medicine Jinling HospitalNanjing University School of MedicineNanjingJiangsuP.R.China department of Oncology Chinese People’s Liberation Army(PLA)General HospitalBeijingP.R.China department of Oncology The Affiliated Hospital of Qingdao UniversityQingdaoShandongP.R.China department of Thoracic Oncology Cancer CenterWest China HospitalSichuan UniversityChengduSichuanP.R.China department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China department of Medical Oncology Cancer HospitalThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityTeaching Hospital of

Background:The initial phase II stuty(NCT032.5693)demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory,anaplastic lymphoma kinase(ALK)-positive non-small cell lung cancer(NSCLC).Herein,we reported the updated data on overall survival(OS)and molecular profiling from the initial phase Ⅱ ***:In this study,180 patients received 2.5 mg of ensartinib orally once daily until disease progression,death or *** was estimated by Kaplan‒Meier methods with two-sided 95%confidence intervals(CIs).Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating *** tumor DNA(ctDNA)was detected to dynamically monitor the genomic alterna-tions during treatment and indicate the existence of molecular residual disease,facilitating improvement of clinical ***:At the data cut-off date(August 31,2.2.),with a median follow-up time of 53.2.months,97 of 180(53.9%)patients had *** median OS was 42.8 months(95%CI:2..3-53.2.months).A total of 333 plasma samples from 168 patients were included for ctDNA *** inferior OS correlated sig-nificantly with baseline ALK or tumor protein 53(Tp53)*** addition,patients with concurrent Tp53 mutations had shorter OS than those without con-current Tp53 *** ctDNA levels evaluated by variant allele frequency(VAF)and haploid genome equivalents per milliliter of plasma(hGE/mL)at baseline were associated with poor ***,patients with ctDNA clear-ance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth,***,patients who had a lower tumor burden,as evaluated by the diameter of target lesions,had a longer *** Cox regression analysis further uncovered the independent prognostic values of bone metastases,higher hGE,and elevated ALK mutation abundance at 6 we

关键词： anaplastic lymphoma kinase ctDNA ensartinib non-small cell lung cancer overall survival