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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 | 常规脂蛋白检测和载脂蛋白在心血管病预测中的比较显示文摘总胆固醇和高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)测量值对于心血管病风险评估至关重要,但对于其他脂质用于风险预测的效用一直存在争议。该研究纳入来自英国生物银行(Biobank)的无基线心血管病、未服用他汀类药物、有相关的脂质指标(n=346 686)的受试者。 | Welsh C Celis-Morales CA Brown R Mackay DF Lewsey J Mark PB Gray SR Ferguson LD Anderson JJ Lyall DM Cleland JG Jhund PS Gill J MR Pell JP Sattar N Welsh P 刘青(译) 叶鹏(摘、审校) | 2019 | 中华高血压杂志2019，27，7： | 10 |
| 3 | Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates显示文摘The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result,several methods to enhance the systemic efficacy of immunotherapy have been investigated,including a large area of active research by combining immunotherapy with radiation therapy(RT).Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit,we review the progress in this field thus far and explore further avenues for enhancing this combination.This review commences with a discussion of the only two existing randomized trials(and a pooled analysis)showing that the addition of RT to immunotherapy improves the abscopal response rate,progression-free survival,and overall survival in metastatic NSCLC patients.We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT,such as low programmed cell death protein ligand 1(PD-L1)status,tumor mutational burden(TMB),and patient’s immune function.Next,the implementation of RT to overcome immunotherapy resistance is discussed,including a mechanistic discussion and methods with which these mechanisms could be exploited.Lastly,the emerging role of low-dose RT is discussed,which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration.Taken together,given the current state of this rapidly expanding realm,these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients. | Shijie Shang Jie Liu Vivek Verma Meng Wu James Welsh Jinming Yu Dawei Chen | 2021 | Cancer Communications2021，41，11： | 10 |
| 4 | Fingerprinting genomes using PCR with arbitrary prim ers显示文摘 | Welsh J | | 0，，： | 3 |
| 5 | Ventilation - induced lung injury is associated with an increase in gut permeability显示文摘 | Guery B P Welsh D A Viget N B | 2003 | Shock2003，19，： | 3 |
| 6 | Genomic fingerprinting using arbitrary primed PCR and a matrix of pairwise combinations of primers显示文摘 | Welsh J McClelland M | 1991 | Nucleic Acids Research1991，19，： | 2 |
| 7 | Evaluation of Long-term Survival After Hepatic Resection for Metastatic Colorectal Cancer: A Multifactorial Model of 929 Patients显示文摘 | Myrddin Rees Paris P. Tekkis Fenella K.S. Welsh Thomas O?Rourke Timothy G. John | 2008 | Annals of Surgery2008，，1： | 2 |
| 8 | Matroid theory显示文摘 | Welsh D J A | 1976 | Acad Press Inc London1976，，： | 2 |
| 9 | 先进封装电镀中活性边界层的减薄显示文摘晶圆表面如果有一层薄且均匀的流体边界层,将有助于克服光刻图形带来的挑战,得到更均匀的金属沉积层。 | Arthur Keigler Zhen Liu Bill Wu Jim Zhang Mark Welsh | 2006 | 集成电路应用2006，23，10： | 2 |
| 10 | Relationship Between the Endophyte Embellisia spp. and the Toxic Alkaloid Swainsonine in Major Locoweed Species (Astragalus and Oxytropis)显示文摘 | M. H. Ralphs R. Creamer D. Baucom D. R. Gardner S. L. Welsh J. D. Graham C. Hart D. Cook B. L. Stegelmeier | 2008 | Journal of Chemical Ecology2008，，1： | 2 |
| 11 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
| 12 | Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small-Cell Lung Cancer Patient Outcomes显示文摘 | Chad Tang Zhongxing Liao Daniel Gomez Lawrence Levy Yan Zhuang Rediet A. Gebremichael David S. Hong Ritsuko Komaki James W. Welsh | 2014 | International Journal of Radiation Oncology, Biology, Physics2014，，： | 2 |
| 13 | 对话:羊毛及羊毛服装的消费取向显示文摘澳大利亚羊毛发展公司是一个非盈利性组织,代表澳大利亚3.5万名羊毛生产者的利益。公司的宪章是推动澳大利亚羊毛可持续增长,在全国范围内推广羊毛的产品开发以及营销,提高羊毛生产者的能力,以及降低成本达到可持续发展。澳大利亚羊毛发展公司业务发展从涉及的领域非常广泛,从基因组的研究到时尚产品的推广,涵盖了整个工业链。到今年的11月,被称为'金羊毛'的澳大利亚美丽诺羊毛已经200岁了。两个世纪以来,澳大利亚凭借'金羊毛'获得了巨大的收益。 | 孟杨 Craig Welsh Pascal Senkoff | 2007 | 纺织服装周刊2007，0，35： | 2 |
| 14 | 无心血管病者尿钠排泄、血压与未来心血管病及死亡风险显示文摘高血压是心血管病的危险因素。代表膳食钠摄入的尿钠排泄增加与血压相关。但在一些观察性研究中,低钠摄入与死亡率增加相关。进一步研究应评估混杂相关性是否能解释钠摄入与预后的关系。研究者分析英国生物银行参加者(n=457484,平均年龄56.3岁,44.7%为男性)尿电解质与血压的数据。采用Kawasaki公式估算每日尿钠排泄量。研究者分析基线无心血管病、治疗的高血压或糖尿病者(n=322624)钠排泄与血压的关系,并评估钠排泄与致死性及非致死性心血管病、心力衰竭及死亡发生率的关系。 | Welsh CE Welsh P Jhund P Delles C Celis-Morales C Lewsey JD Gray S Lyall D Iliodromiti S Gill JMR Sattar N Mark PB 赵狄 练桂丽 | 2019 | 中华高血压杂志2019，27，6： | 2 |
| 15 | Fingerprinting genomes using PCR with arbitrary primers显示文摘 | Welsh J Meclelland M | 1990 | Nucl Acid Res1990，18，： | 2 |
| 16 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
| 17 | A Tensile Testing Technique for Fiber-Reinforced Composites at Impact Rates of Strain 显示文摘 | Harding J Welsh L M | 1983 | Journal of Materials Science1983，18，6： | 1 |
| 18 | Large - scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum 显示文摘 | Welsh JB Sapinoso LM Kern SG | 2003 | Proc Natl Acad Sci USA2003，100，： | 1 |
| 19 | Immuno- logenicity of human amniotic epithelial cells after transplantation into volunteers 显示文摘 | Aide CA Adinolfi M Welsh KI | 1981 | Lancet1981，2，： | 1 |
| 20 | Fingerprinting genornes using PCR with arbitrary primers显示文摘 | McCLELLAND M | 1990 | Nucl Acids Res1990，18，24： | 1 |
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