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| 1 | 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显示文摘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<10年组和≥10年组)。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ClinicalTrials.gov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。 | 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 | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study显示文摘 | Axel Bauer Jan W Kantelhardt Petra Barthel Raphael Schneider Timo M?kikallio Kurt Ulm Katerina Hnatkova Albert Sch?mig Heikki Huikuri Armin Bunde Marek Malik Georg Schmidt | 2006 | The Lancet2006，，9523： | 3 |
| 3 | CD133 expression is not restricted to stem cells, and both CD133^sup +^ and CD133^sup -^ metastatic colon cancer cells initiate tumors显示文摘 | Shmelkov Sergey V Butler Jason M Hooper Andrea T Hormigo Adilia Kushner Jared Milde Till Clair Ryan St Baljevic Muhamed White Ian Jin David K Chadburn Amy Murphy Andrew J Valenzuela David M Gale Nicholas W Thurston Gavin Yancopoulos George | 2008 | Journal of Clinical Investigation2008，，： | 2 |
| 4 | Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study显示文摘BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine. | Nicholas V Mendez Yehuda Raveh Joshua J Livingstone Gaetano Ciancio Giselle Guerra George W Burke III Vadim B Shatz Fouad G Souki Linda J Chen Mahmoud Morsi Jose M Figueiro Tony M Ibrahim Werviston L DeFaria Ramona Nicolau-Raducu | 2021 | World Journal of Transplantation2021，11，4： | 2 |
| 5 | Rapid evolution of animal mitochondrial DNA 显示文摘 | BROWN W M GEORGE J R WILSON A C | 1979 | Proc Nat Acad Sci USA1979，76，19： | 2 |
| 6 | Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression显示文摘 | Jason M Hui Archana Sud Geoffrey C Farrell Priyanka Bandara Karen Byth James G Kench Geoffrey W McCaughan Jacob George | 2003 | Gastroenterology2003，，6： | 2 |
| 7 | Comprehensive, quantitative, congener-specific analysis of eight aroclors and complete PCB congener assignments 显示文摘 | George M F Robert E W James C C | 1996 | Chernosphere1996，33，： | 1 |
| 8 | Labeling products of complete graphs with a condition at distance two 显示文摘 | GEORGES J P MAURO D W STEIN M I | 2000 | SIAM J Discrete Math2000，14，1： | 1 |
| 9 | Isolation of anticoag ulant fractions from crude fucoidin显示文摘 | Georg F S Harold A W George M | 1957 | Experimental Biology and Medicine1957，94，2： | 1 |
| 10 | Bio- marker evidence for two sources for solid bitumens in the Subu wells~Implications for the petroleum prospectivity of the East Papuan Basin 显示文摘 | George SC Volk H Ahmed M Pickel W Allan T | 2007 | Organic Geochemistry2007，38，： | 1 |
| 11 | Lipase-catalyzed Hydrolysis as a Route to Esters of Chiral Epoxy Alcohols 显示文摘 | George M W | 1984 | J Am Chem Soc1984，106，： | 1 |
| 12 | Packing different-sized circles into a rectangular container显示文摘 | George J A George J M Lamar B W | 1995 | European Journal of Operational Research1995，84，3： | 1 |
| 13 | Rapid evolution of animal mitochondrial DNA显示文摘 | Brown W M George M J Wilson A C | 1989 | Trend Ecol Evol1989，4，： | 1 |
| 14 | Predictive models of the effect of temperature, pH and acetic and lactic acids on the growth of Listeria moocytogene显示文摘 | George S M Richardson Laura C C Peck M W | 1996 | International Journal of Food Microbiology1996，32，： | 1 |
| 15 | Effects of Biodegradation on Australian Permain coals 显示文摘 | Ahmed M Smith J W George C | 1999 | Organic Geochemistry1999，30，： | 1 |
| 16 | Kinetic Resolution of Racemic Glycidyl Butyrate Using a Multiphase Membrane and Model Verification 显示文摘 | Steven M C Georges B | 1993 | Biotechnology and Bioengeering1993，41，： | 1 |
| 17 | The influence of water level fluctuations on the growth of four emergent macrophyte species 显示文摘 | Brian M D Sean D W George G G | 2007 | Aquatic Botany2007，86，4： | 1 |
| 18 | Genotypic variation for Potassium uptake and utilization effieieney in sweet potato显示文摘 | George M S Lu G Q Zhou W J | 2002 | Field Crops Research2002，77，1： | 1 |
| 19 | Health Effects of Nonionizing Radiation 显示文摘 | GEORGE M W CARL H S | 1990 | Environ Med1990，74，5： | 1 |
| 20 | Intensity-modulated radiotherapy with use of cone-down boost for pediatric head-and-neck rhab domyosarcoma显示文摘 | MCDONALD M W ESIASHVILI N GEORGE BA | 2008 | Int J Radiat Oncol Biol Phys2008，721，： | 1 |
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