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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 | PIV measurements of turbulent jets issuing from triangular and circular orifice plates显示文摘The present study experimentally investigated the near-field flow mixing characteristics of two turbulent jets issuing from equilateral triangular and circular orifice plates into effectively unbounded surroundings,respectively.Planar particle image velocimetry(PIV) was applied to measure the velocity field at the same Reynolds number of Re=50,000,where Re = UeDe /with Ue being the exit bulk velocity and the kinematic viscosity of fluid,D e the equivalent diameters.The instantaneous velocity,mean velocity,Reynolds stresses were obtained.From the mean velocity field,the centreline velocity decay rate and half-velocity width were derived.Comparing the mixing characteristics of the two jets,it is found that the triangular jet has a faster mixing rate than the circular counterpart.The triangular jet entrainments with the ambient fluid at a higher rate in the near field.This is evidenced by a shorter unmixed core,faster Reynolds stress and centreline turbulence intensity growth.The primary coherent structures in the near field are found to break down more rapidly in the triangular jet as compared to the circular jet.Over the entire measurement region,the triangular jet maintained a higher rate of decay and spread.Moreover,all components of Reynolds stress of the triangular jet appear to reach their peaks earlier,and then decay more rapidly than those of the circular jet.In addition,the axis-switching phenomenon is observed in the triangular jet. | XU MinYi ZHANG JianPeng MI JianChun NATHAN G J KALT P A M | 2013 | Science China(Physics,Mechanics & Astronomy)2013，56，6： | 7 |
| 3 | The effect of different initial conditions on the exit flow from a fluidic precessing jet nozzle显示文摘 | Wong C Y Nathan G J O' Doherty T | 2003 | Experiments in Fluids2003，36，： | 1 |
| 4 | A Phase Ib trial of CA4P (combretastatin A-4 phosphate),carboplatin,and paclitaxel in patients with advanced cancer显示文摘 | Rustin G J Shreeves G Nathan P D | 2010 | Br J Cancer2010，102，9： | 1 |
| 5 | Mixing characteristics of axisymmetric free jets from a contoured nozzle, an orifice plate and a pipe显示文摘 | Mi J Nathan G J Nobes D S | 2001 | Transactions of the ASME2001，123，： | 1 |
| 6 | Femtosecond laser‐assisted cataract surgery compared with conventional cataract surgery显示文摘 | Robin G Abell Nathan M Kerr Brendan J Vote | 2013 | Clin Experiment Ophthalmol2013，，5： | 1 |
| 7 | Nerve root compression in spondylolysis and spondylolisthesis显示文摘 | EDELSON J G NATHAN H | 1986 | J Bone Joint Surg[Br]1986，68，： | 1 |
| 8 | A method for computing lexical semantic distance using linear functionals显示文摘 | DEL J CHRISTOPHE G C NATHAN D | 2008 | Semantic Multimedia2008，6，2： | 1 |
| 9 | Effect of a uniform electric field on soot in laminar premixed ethylene/air flames 显示文摘 | WANG Y NATHAN G J ALWAHABI Z | 2010 | Combust Flame2010，157，7： | 1 |
| 10 | A randomized, Double-blind, Placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit显示文摘 | Wiener J Itokazu G Nathan C | 1995 | Clin Infect Dis1995，20，4： | 1 |
| 11 | The Influence of Inlet Flow Condition on the Frequency of Self-excited Jet Precession显示文摘 | Mi J Nathan J G Wong C Y | 2006 | Journal of Fluids and Structures2006，22，： | 1 |
| 12 | Requirement for donor and recipient CD40 expression in cardiac allograft rejection:induction of Th1 responses and influence of donor-derived dendritic cells显示文摘 | Nathan M J Mold JE Wood SC Csencsits K Lu G Eichwald E J | | 0，，11： | 1 |
| 13 | Olfactory function in apoE knockout mice显示文摘 | Nathan B P Yost J Litherland M T Struble R G Switzer P V | 2004 | Behav Brain Res2004，150，12： | 1 |
| 14 | Opera- tional characteristics of a parallel jet MILD combus- tion burner system 显示文摘 | SZEGO G G DALLY B B NATHAN G J | 2009 | Combustion and Flame2009，156，2： | 1 |
| 15 | The influence of nozzle aspect ratio on plane jets显示文摘 | Deo R C Nathan G J Mi J | | 0，，08： | 1 |
| 16 | The management of temperature during cardiopulmonary bypass: effect on neurophychological outcome显示文摘 | Nathan H J Munson J Wells G | 1995 | J Cardiovasc Surg1995，36，4： | 1 |
| 17 | Scaling of NOx emissions from a laboratory-scale mild combustion furnace显示文摘 | Szego G G Dally B B Nathan G J | 2008 | Combustion and Flame2008，154，12： | 1 |
| 18 | The neuropharm acology of L-theanine ( N-ethyl-L-glutamine ) : apossible neuroprotective and cognitive enhancing agent 显示文摘 | Nathan P J Lu K G ray M | 2006 | J Herbal Pharmacother2006，6，： | 1 |
| 19 | Influence of the hardness of abrasive on the abrasive wear of metals显示文摘 | G K Nathan W J Jones | 1966 | Proc Instn Mech Engrs1966，181，： | 1 |
| 20 | Statistical properties of turbulent free jets issuing from nine differently-shaped nozzles 显示文摘 | Mi J Nathan G J | 2010 | Flow Turbulence and Combustion2010，84，4： | 1 |
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