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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 | Formaldehyde over the central Pacific during PEM-Tropics B显示文摘 | Heikes B Snow J Egli P | 2001 | GeoP hys Res2001，106，32： | 1 |
| 3 | RNA Transfer by electroporation into mature dendritic cells leading to reactivation of effector-memorycytotoxlc T lymphocytes: A quantitative analysis 显示文摘 | Miran J Heike P Bernhard F | 2005 | Mole Ther2005，12，4： | 1 |
| 4 | 显示文摘 | TATIANA A S HEIKE M SERGIY A P | 2001 | J Chromatogr A2001，907，： | 1 |
| 5 | Gas phase detection of explosives such as 2,4,6-trinitrotoluene by molecularly imprinted polymers 显示文摘 | Gudrun B Jurgen H Heike P | 2007 | Analytiea Chimiea Aeta2007，，591： | 1 |
| 6 | Structural incorporation of Cm(Ⅲ) in trioctahedral smectite hectorite: A time-resolved laser fluorescence spectroscopy (TRLFS) study 显示文摘 | HEIKE B DIRK B PETRA J P | 2007 | Geochim Cosmochim Acta2007，71，1： | 1 |
| 7 | Cryptopatches and isolated lymphoid follicles:dynamic lymphoid tissues dispensable for the generation of intraepithelial lymphocytes显示文摘 | Oliver P Heike H TimW | 2005 | Eur J Immunol2005，35，1： | 1 |
| 8 | Anatomical variation of five plant species along an elevation gradient in Mexico City basin within the Trans-Mexican Volcanic Belt, Mexico显示文摘Change in environmental conditions with altitudinal gradients induces morpho-anatomical variations in plants that have been poorly documented in intertropical regions. Five species with three life forms, cryptophyte(Alchemilla procumbens, Geranium seemannii), hemicryptophyte(Acaena elongata, Lupinus montanus), and phanerophyte(Symphoricarpos microphyllus), distributed along an altitudinal gradient in the Sierra Nevada of central Mexico, were studied. The aims were to identify and evaluate their morpho-anatomical modifications under the hypothesis that the sizes of individuals and of their wood and leaf cell types decrease as elevation increases. Three individuals per species per site were collected at seven locations along the altitudinal gradient(2949-3952 m). Their morpho-anatomical characters were analyzed through multiple regression analyses. Elevation was the variable that best explained anatomical changes in the leaf and wood ofthe five species. Canopy density and potassium content in the soil also contributed to explain the variation in anatomical variables along the gradient. As elevation increased a bimodal pattern was observed in various anatomical characters as in the leaf width of A. elongata, A. procumbens and G. seemannii and in the vessel diameter of A. procumbens, G. seemannii, and L. montanus. Other features as the vessel diameter of A. elongata, the fiber length of S. microphyllus, and the ray width of A. elongata increased as the elevation increased. Anatomical traits have a tendency to decrease in size but just toward the end of the gradient, which is probably related to changes in canopy density. The plant response to the altitudinal gradient is more focused on anatomical adaptations than morphological variation; it is also species dependent. | P Mayte S.JIMéNEZ-NORIEGA Teresa TERRAZAS Lauro LóPEZ-MATA Arturo SáNCHEZ-GONZáLEZ Heike VIBRANS | 2017 | Journal of Mountain Science2017，14，11： | 1 |
| 9 | The replacement of Trp392 by alanine influences the decarboxylase/ carboligase activity and stability of pyruvate decarboxylase from Zymomonas mobilis 显示文摘 | Heike B Martina P Joachim G | 1995 | Eur J Biochem1995，234，： | 1 |
| 10 | Eu (III) coprecipitation with the trioetahedral clay mineral, heetorite 显示文摘 | Heike P Bosbach D Panak P J | 2006 | Clays and Clay Minerals2006，54，1： | 1 |
| 11 | Molecularly imprinted polymer membranes for substance-selective solid-phase extraction from water by surface photo-grafting polymerization显示文摘 | Tatiana A S Heike Matuschewski Sergiy A P etc | 2001 | J Chromat A2001，907，： | 1 |
| 12 | Nitrogen transfer in the arbuscular mycorrhizal symbiosis 显示文摘 | Manjula G Philip E P Hairu J Jehad A David D D James W A Heike B Peter J L Yair S H | 2005 | Nature2005，435，： | 1 |
| 13 | Climate Modeling with Spherical Geodesic Grids显示文摘 | RANDALL D A RINGLER T D HEIKES R P | 2002 | Computing in Science & Engineering2002，，： | 1 |
| 14 | FDTD modeling of a novel ELF radar for major oil deposits using a three-dimensional geodesic grid of the earth-ionosphere waveguide 显示文摘 | Simpson J J Heikes R P Taflove A | 2006 | IEEE Trans Antennas and Propagation2006，54，6： | 1 |
| 15 | Pykl0, a seedling and root specific gene and promoter from Arabidopsis thaliana显示文摘 | Inke N Heike B Piotr S P | 2001 | Plant Science2001，，161： | 1 |
| 16 | Monte carlo simulation of observation time-dependent self-diffusion in porous media models显示文摘 | REGIER M HEIKE S P | 2005 | Transp Porous Med2005，59，： | 1 |
| 17 | Organic-inorganic multilayer structures:A novel route to highly efficient organic light- emitting diodes显示文摘 | Heike R Seidler P F | 1999 | Synthetic Metals1999，99，3： | 1 |
| 18 | VEGFR--3 and VEGF-- C are associated with angiogenesis in breast cancer 显示文摘 | Valtola R Salven P Heik kila P | 1999 | Am J Pathol1999，154，5： | 1 |
| 19 | Vascular K<sub>Ca</sub>-channels as therapeutic targets in hypertension and restenosis disease显示文摘 | Ralf K?hler Brajesh P Kaistha Heike Wulff | 2010 | Expert Opinion on Therapeutic Targets2010，，2： | 1 |
| 20 | Depression among caregivers of stroke survivors显示文摘 | Anu!B Heik ki P Jouko I | 2005 | Stroke2005，36，3： | 1 |
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