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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 | Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study显示文摘 | Patrick Marcellin Edward Gane Maria Buti Nezam Afdhal William Sievert Ira M Jacobson Mary Kay Washington George Germanidis John F Flaherty Raul Aguilar Schall Jeffrey D Bornstein Kathryn M Kitrinos G Mani Subramanian John G McHutchison E Jenny Heathcote | 2012 | The Lancet2012，，： | 14 |
| 3 | Ordered Intermetallics显示文摘 | E P George M Yamaguchi K S Kumar C T Liu | 1994 | Annual Review of Materials Science1994，，： | 2 |
| 4 | Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders显示文摘 | E Joanna Baxter Linda M Scott Peter J Campbell Clare East Nasios Fourouclas Soheila Swanton George S Vassiliou Anthony J Bench Elaine M Boyd Natasha Curtin Mike A Scott Wendy N Erber Anthony R Green | 2005 | The Lancet . 2005 (9464)2005，，： | 2 |
| 5 | Increasing diabetes self-management education in community settings显示文摘 | Susan L Norris Phyllis J Nichols Carl J Caspersen Russell E Glasgow Michael M Engelgau Leonard Jack Susan R Snyder Vilma G Carande-Kulis George Isham Sanford Garfield Peter Briss David McCulloch | 2002 | American Journal of Preventive Medicine2002，，4： | 2 |
| 6 | 利用天然气的碳同位素比值建立热成因气模型显示文摘利用同位素模型预测甲烷、乙烷和丙烷的δ^(13)C值(干酪根/油生成气态物的程度指标),并用于指示Ⅱ型干酪根的生气特征。通过把气体的多组份动力学模型与同位素模型相结合,可得到气体组份转化率与生成温度之间的相关性。δ^(13)C_1,δ^(13)C_2和δ^(13)C_3之间的关系式利用天然气的热解模型进行限制。通过西得克萨斯Delaware和Val Verde盆地海相腐泥型页岩(Ⅱ型干酪根)生成的气体数据对同位素模型进行验证与校对。这些气体相对不受运移和生物气的混合影响,所以,气体碳同位素比值的变化能初步反映成熟度的演化程度。因此,这些数据对解释气体生成温度和来源于Ⅱ型干酪根的气体δ^(13)C值是有实际价值的。 | Melodye A R George E C Chung H M 刘全有 | 2002 | 天然气地球科学2002，13，5： | 2 |
| 7 | Stability of fruit quality traits in diverse watermelon cultivars tested in multiple environments显示文摘Lycopene is a naturally occurring red carotenoid compound that is found in watermelon.Lycopene has antioxidant properties.Lycopene content,sugar content and hollowheart resistance are subject to significant genotype×environment interaction(G×E),which makes breeding for these fruit quality traits difficult.The objectives of this study were to(i)evaluate the influence of years and locations on lycopene content,sugar content and hollowheart resistance for a set of watermelon genotypes,and(ii)identify genotypes with high stability for lycopene,sugar,and hollowheart resistance.A diverse set of 40 genotypes was tested over 3 years and 8 locations across the southern United States in replicated,multi-harvest trials.Lycopene was tested in a subset of 10 genotypes.Data were analyzed using univariate and multivariate stability statistics(BLUP-GGE biplot)using SASGxE and RGxE programs.There were strong effects of environment as well as G×E interaction on watermelon quality traits.On the basis of stability measures,genotypes were classified as stable or unstable for each quality trait.'Crimson Sweet'is an inbred line with high quality trait performance as well as trait stability.'Stone Mountain','Tom Watson','Crimson Sweet'and'Minilee'were among the best genotypes for lycopene content,sugar content and hollowheart resistance.We developed a stability chart based on marketable yield and average ranking generated from different stability measures for yield attributes and quality traits.The chart will assist in choosing parents for improvement of watermelon cultivars.See http://gffzz783b6e01a04243c3hcwkk5kcqvkpc6bbb.ffgz.tsg.suse.edu.cn/cucurbit/wmelon/wmelonmain.html. | Mahendra Dia Todd C Wehner Penelope Perkins-Veazie Richard Hassell Daniel S Price George E Boyhan Stephen M Olson Stephen R King Angela R Davis Gregory E Tolla Jerome Bernier Benito Juarez | 2016 | Horticulture Research2016，3，1： | 2 |
| 8 | 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 |
| 9 | A mechanism for Pglycoprotein-mediated apoptosis as by Verapamil hypersensitivity 显示文摘 | Karwatsky J Lincoln M C Georges E | 2003 | Biochemistry2003，42，12： | 1 |
| 10 | Novel role of NF-kap- paB-p65 in antioxidant homeostasis in human kidney-2 cells显示文摘 | George L E Lokhandwala M F Asghar M | 2012 | Am J Physiol Renal Physiol2012，302，11： | 1 |
| 11 | The ecology of medical care revisited显示文摘 | Larry A Green George E Fryer Jr Barbara P Yawn David lanier Susan M Dovey | 2001 | The New England Journal of Medicine2001，334，26： | 1 |
| 12 | Constraining the oil charge history of the South Pepper oilfield from the analysis of oil-bearing fluid inclusions显示文摘 | George S C Lisk M Sunnons R E | 1998 | Organic Geochemistry1998，29，： | 1 |
| 13 | CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients显示文摘 | Savoldo Barbara Ramos Carlos Almeida Liu Enli Mims Martha P Keating Michael J Carrum George Kamble Rammurti T Bollard Catherine M Gee Adrian P Mei Zhuyong Liu Hao Grilley Bambi Rooney Cliona M Heslop Helen E Brenner Malcolm K Dotti Gianpie | 2011 | Journal of Clinical Investigation2011，，5： | 1 |
| 14 | pH sensitive alginate - guar gum hydrogel forthe controlled delivery of protein drugs显示文摘 | George M Abraham T E | 2007 | International Journal of Pharmaceutics2007，335，12： | 1 |
| 15 | 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 |
| 16 | Locked knee caused by meniscal subluxation:magnetic resonance imaging and arthroscopic verification显示文摘 | George M Wall E J | 2003 | Arthroscopy2003，19，8： | 1 |
| 17 | The Innas hydraulic transformer: the key to the hydrostatic common pressure rail显示文摘 | Vael Georges E M Achten P A J Fu Zhao | 2000 | SAE2000，，01： | 1 |
| 18 | Serum hyaluronic acidlevel as a predictor of disease progression in osteoarthritis of theknee 显示文摘 | Sharif M George E Shepstone L | 1995 | Arthritis Rheum1995，38，6： | 1 |
| 19 | Approaches for thesimultaneous detection of thiamphenicol, florfenicol and florfeni-col amine using immunochemical techniques显示文摘 | Fodey T L George S E Traynor I M | 2013 | J Immunol Meth-ods2013，393，12： | 1 |
| 20 | Tumor patients in psychodynamic psychotherapy including daydreaming: can imagery enhance primary process and positive emotions? 显示文摘 | Frick E Stigler M Georg H | 2008 | Psychother Res2008，18，4： | 1 |
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