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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 | Preparation of stable micropatterns of gold on cell-adhesion-resistant hydrogels assisted by a hetero-bifunctional macromonomer linker显示文摘Surface patterning is very useful in biomaterial studies, yet it is not easy to prepare a micropattern with cell-adhesion contrast that is stable in a wet environment. Recently, a platform technique of transfer photolithography was invented to fabricate stable metal microarrays on the surface of a cell-adhesion resistant and mechanically biomimetic poly(ethylene glycol) hydrogel; the linker is the key chemical in such a transfer strategy. This article reports the design and synthesis of a hetero-bifunctional macromonomer linker with a thiol group at one end and an acryloyl group at the other end. The bifunctional linker was characterized by GPC and 1H NMR, and the average number of thiol groups in the bifunctional linker was detected by Ellman's reagent. The regent stability under wet conditions was also confirmed by the model reactants. The resultant micropatterned surfaces are meaningful for future studies of cell behaviors on mechanically biomimetic matrixes. | SUN JianGuo GRAETER Stefan V TANG Jian HUANG JingHuan LIU Peng LAI YuXiao YU Lin MAJER Günter SPATZ Joachim P DING JianDong | 2014 | Science China Chemistry2014，57，4： | 2 |
| 3 | Cardiac hypertrophy:Targe- ting Raf/MEK/ERKl/2-signa]ing显示文摘 | KRISTINA L JOACHIM P | 2009 | Int J Bioehem Cell Biolo- gy2009，41，： | 1 |
| 4 | Radiation effects on poly (lactide-co-glycolide) ( PLGA ) and poly ( L-lactide ) (PLLA) 显示文摘 | Joachim L S C Ooi C P Freddy B Y C | 2004 | Polym Degrad Stab2004，83，2： | 1 |
| 5 | Structure, composition, and mechanical properties of shark teeth显示文摘 | Joachim E Oleg P Dierk R | 2012 | Journal of Structural Biology2012，178，3： | 1 |
| 6 | Reumatoid arthritis and postifsonalvertehrobasilar insufficiency显示文摘 | Burke P Joachim F steren M | 1986 | Jneurosury1986，65，1： | 1 |
| 7 | Reumatoid arthritis and positional vertebrobasilar insufficiency显示文摘 | Joachim F steren M | 1986 | J Neurosurgery1986，65，1： | 1 |
| 8 | Prediction and assessment of the effects of mixtures of four xenoestrogens 显示文摘 | Joachim P Nissanka R Megan W | 2000 | Environ Health Perspect2000，108，： | 1 |
| 9 | Design and analysis of verticalcavity semiconductor optical amplifiers 显示文摘 | JOACHIM P STAFFAN B JOHN E B | 2001 | IEEE J Q E2001，37，1： | 1 |
| 10 | Antithymocyte globulin with or without cyclosporin A:11-year follow-up of a randomized trial comparing treatments of aplastic anemia显示文摘 | Norbert F Hermann H Joachim P | 2003 | Blood2003，101，4： | 1 |
| 11 | Active Damping of Drive Train Oscillations for an Electrically Driven Vehicle 显示文摘 | Notker A Joachim B Franz P | 2004 | IEEE/ASME Transaction on Mechatronics2004，9，4： | 1 |
| 12 | Smooth image segmentation by nonparametric bayesian inference 显示文摘 | Orbanz P Joachim M Buhmann | 2006 | International Journal of Computer Vision2006，3951，1： | 1 |
| 13 | Antithymocyte globulin with or without cyclosporin A:11-year follow-up of arandomized trial comparing treatments of aplastic anemia显示文摘 | Norbert F Hermann H Joachim P | 2003 | BLOOD2003，101，4： | 1 |
| 14 | Phase Ⅲ study comparing cisplatin plus gcmcitabine with cisplatin plus pemetrexed in chemo- thcrapy-naive patients with advanced-stage non small-cell lung can- cer 显示文摘 | Giorgiol V Purvish P Joachim VP | 2008 | Journal of Clinical Neology2008，26，21： | 1 |
| 15 | An Algebraic Verification of a Mobile Network显示文摘 | FREDRIK O JOACHIM P | 1996 | Journal of Formal Aspects of Computing1996，3，3： | 1 |
| 16 | European consumers'use of and trust in information sources about fish 显示文摘 | Zuzanna P Verbeke W Joachim S | 2007 | Food Quality and Preference2007，18，： | 1 |
| 17 | Tuberculous brain abscess显示文摘 | Gonzalez P Herrero C Joachim G | 1980 | Neurosurgery1980，52，3： | 1 |
| 18 | Surgical resection of pulmonary metastases from colorectal cancer:a systematic review of published series显示文摘 | JOACHIM P HENDRIK D HANS H | 2007 | Ann Thorac Surg2007，84，： | 1 |
| 19 | Phase Ⅲ study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-na?ve patients with advanced-stage non small-cell lung cancer显示文摘 | Giorgiol V Purvish P Joachim VP | 2008 | Journal of Clinical Ncology2008，26，21： | 1 |
| 20 | Reumatoid arthritis and positional vertebrobasilar insufficiency显示文摘 | Burke P Joachim F steren M | 1986 | J eurosurgery1986，65，1： | 1 |
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