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帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析

中华肿瘤防治杂志 2021年第24期28卷 1841-1850页

作者：陈大卫(翻译) 于金明(校对) willemijn s m e theelen Vivek Verma Brian P Hobbs Heike m U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia m de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R simon Ferdinandos skoulidis steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 山东省肿瘤防治研究院(山东省肿瘤医院) 山东第一医科大学(山东省医学科学院)山东济南250117 不详 Department of Radiation Oncology The University of Texas M D Anderson Cancer CenterHoustonTX 77030USA

背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PemBRO-RT研究和Ⅰ/Ⅱ期mDACC研究中,患有转移性非小细胞肺癌(NsCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,... 详细信息

背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PemBRO-RT研究和Ⅰ/Ⅱ期mDACC研究中,患有转移性非小细胞肺癌(NsCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NsCLC患者的免疫治疗应答。方法PemBRO-RT和mDACC研究纳入标准:患者年龄≥18岁,患有转移性NsCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PemBRO-RT研究纳入曾接受过化疗患者,mDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PemBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为mDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PemBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在mDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFs)和总生存期(Os)。2个研究的意向治疗(ITT)人群均纳入分析。PemBRO-RT研究(NCT02492568)和mDACC研究(NCT02444741)均在***上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFs中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;Os中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NsCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。

关键词：帕博利珠单抗非小细胞肺癌放疗汇总分析

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The world’s ten most feared fungi

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Fungal Diversity 2018年第6期93卷 161-194页

作者： Kevin D.Hyde Abdullah m.s.Al-Hatmi Birgitte Andersen Teun Boekhout Walter Buzina Thomas L.Dawson Jr. Dan C.eastwood e.B.Gareth Jones sybren de Hoog Yingqian Kang Joyce e.Longcore eric H.C.mcKenzie Jacques F.meis Laetitia Pinson-Gadais Achala R.Rathnayaka Florence Richard-Forget marc stadler Bart theelen Benjarong Thongbai Clement K.m.Tsui Key Laboratory for Plant Diversity and Biogeography of east Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanPeople’s Republic of China Center of excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand ministry of Health Directorate General of Health ServicesIbriOman Department of Biotechnology and Biomedicine Technical University of Denmark2800 Kgs.LyngbyDenmark Institute for Biodiversity and ecosystem Dynamics(IBeD) University of AmsterdamAmsterdamThe Netherlands Westerdijk Fungal Biodiversity Institute UtrechtThe Netherlands R&D Institute for Hygiene Microbiology and Environmental MedicineMedical University GrazNeue Stiftingtalstrasse 68010 GrazAustria Institute for medical Biology(ImB) Agency for ScienceTechnologyand Research(A_(*)STAR)SingaporeSingapore Departments of Drug Discovery and Biomedical sciences and Biochemistry and molecular Biology Center for Cell DeathInjury and RegenerationMedical University of South CarolinaCharlestonSCUSA Department of Bioscience Academic Office102First FloorWallace BuildingSwansea UniversitySingleton CampusSwanseaWalesUK Centre of expertise in mycology Radboudumc/Canisius Wilhelmina Hospital(CWZ) NijmegenThe Netherlands Portsmouth Hampshire PO53DHUK Department of microbiology and the Key Laboratory of Proteomics Guizhou Medical UniversityGuiyangChina school of Biology and ecology University of MaineOronoME 04469USA manaaki Whenua-Landcare Research Private Bag 92170AucklandNew Zealand Department of medical microbiology and Infectious Diseases Canisius Wilhelmina Hospital(CWZ)NijmegenThe Netherlands INRA UR1264 MycSA71 av Edouard Bourlaux2003233882 Villenave D’Ornon CedexFrance Department microbial Drugs Helmholtz Centre for Infection Researchand German Centre for Infection Research(DZIF)Partner Site Hannover-BraunschweigInhoffenstraße 738124 BraunschweingGermany Department of Pathology Sidra MedicineDohaQatar Department of Pathology and Laboratory medicine Weill Corne

An account is provided of the world’s ten most feared *** areas of interest,we have organized the entries in the order of *** put four human pathogens first as this is of concern to most *** is followed by fungi producing mycotoxins that are highly harmful for humans;Aspergillus flavus,the main producer of aflatoxins,was used as an *** due to indoor air fungi may also directly affect our health and we use stachybotrys chartarum as an *** everyone collects and eats edible ***,fatalities caused by mushroom intoxications often make news headlines and therefore we include one of the most poisonous of all mushrooms,Amanita phalloides,as an *** then move on to the fungi that damage our dwellings causing serious anxiety by rotting our timber structures and *** lacrymans,which causes dry rot is an excellent *** next example serves to represent all plant and forest *** we chose Austropuccinia psidii as it is causing devastating effects in Australia and will probably do likewise in New ***,we chose an important amphibian pathogen which is causing serious declines in the numbers of frogs and other amphibians *** we target the top ten most feared fungi,numerous others are causing serious concern to human health,plant production,forestry,other animals and our factories and *** highlighting ten feared fungi as an example,we aim to promote public awareness of the cost and importance of fungi.

关键词： Aflatoxicosis Batrachochytrium Candida auris Frog decline Poisonous fungi Human pathogens Indoor fungi Forest pathogens Wood decay

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Delimiting species in Basidiomycota:a review

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Fungal Diversity 2021年第4期109卷 181-237页

作者： Bin Cao Danny Haelewaters Nathan schoutteten Dominik Begerow Teun Boekhout Admir J.Giachini sergio P.Gorjón Nina Gunde-Cimerman Kevin D.Hyde martin Kemler Guo-Jie Li Dong-mei Liu Xin-Zhan Liu Jorinde Nuytinck Viktor Papp Anton savchenko Kyryll savchenko Leho Tedersoo Bart theelen marco Thines michal Tomšovský merje Toome-Heller Judith P.Urón Annemieke Verbeken Alfredo Vizzini Andrey m.Yurkov Juan Carlos Zamora Rui-Lin Zhao state Key Laboratory of mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Faculty of science University of South Bohemia37005ČeskéBudějoviceCzech Republic Research Group mycology Department of BiologyGhent University9000 GhentBelgium Department of Botany and Plant Pathology College of AgriculturePurdue UniversityWest LafayetteIN 47907USA Department of Geobotany Ruhr-Universität Bochum44801 BochumGermany Westerdijk Fungal Biodiversity Institute 3508 AD UtrechtThe Netherlands Institute of Biodiversity and ecosystem Dynamics University of Amsterdam1090 GE AmsterdamThe Netherlands Department of microbiology Universidade Federal de Santa CatarinaFlorianópolisSC 88040-900Brazil Department of Botany and Plant Physiology University of Salamanca37007 SalamancaSpain Department of Biology Biotechnical FacultyUniversity of Ljubljana1000 LjubljanaSlovenia Center of excellence in Fungal Research Mae Fah Luang UniversityChiang Rai 57100Thailand Innovative Institute of Plant Health Zhongkai University of Agriculture and EngineeringHaizhu DistrictGuangzhou 510225China CAs Key Laboratory for Plant Diversity and Biogeography of east Asia Kunming Institute of BotanyChinese Academy of ScienceKunming 650201YunnanChina Key Laboratory of Vegetable Germplasm Innovation and Utilization of Hebei Collaborative Innovation Center of VegetableCollege of HorticultureHebei Agricultural UniversityBaoding 071001Hebei ProvinceChina Institute of ecology Chinese Research Academy of Environmental SciencesBeijing 100012China Naturalis Biodiversity Center 2300 RA LeidenThe Netherlands Department of Botany Institute of AgronomyHungarian University of Agriculture and Life Sciences1518 BudapestHungary Institute of ecology&earth sciences University of Tartu51014 TartuEstonia Department of Biological sciences Butler UniversityIndianapolisIN 46219USA Center of mycology and microbiology University of Tartu14a Ravila50411 TartuEstonia senckenberg Biodiversity and Climate Researc

species delimitation is one of the most fundamental processes in *** undertakings,for instance,require explicit species concepts and criteria for species delimitation in order to be relevant and ***,a perfect species concept does not exist for ***,we review the species concepts commonly used in Basidiomycota,the second largest phylum of Fungi that contains some of the best known species of mushrooms,rusts,smuts,and jelly *** general,best practice is to delimitate species,publish new taxa,and conduct taxonomic revisions based on as many independent lines of evidence as possible,that is,by applying a so-called unifying(or integrative)conceptual ***,the types of data used vary considerably from group to *** this reason we discuss the different classes of Basidiomycota,and for each provide:(i)a general introduction with difficulties faced in species recognition,(ii)species concepts and methods for species delimitation,and(iii)community recommendations and conclusions.

关键词： Biological species concept morphological species concept Phylogenetic species concept Taxonomy

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