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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 | Antenna-assisted picosecond control of nanoscale phase transition in vanadium dioxide显示文摘Nanoscale devices in which the interaction with light can be configured using external control signals hold great interest for next-generation optoelectronic circuits.Materials exhibiting a structural or electronic phase transition offer a large modulation contrast with multi-level optical switching and memory functionalities.In addition,plasmonic nanoantennas can provide an efficient enhancement mechanism for both the optically induced excitation and the readout of materials strategically positioned in their local environment.Here,we demonstrate picosecond all-optical switching of the local phase transition in plasmonic antenna-vanadium dioxide(VO_(2))hybrids,exploiting strong resonant field enhancement and selective optical pumping in plasmonic hotspots.Polarization-and wavelength-dependent pump–probe spectroscopy of multifrequency crossed antenna arrays shows that nanoscale optical switching in plasmonic hotspots does not affect neighboring antennas placed within 100 nm of the excited antennas.The antenna-assisted pumping mechanism is confirmed by numerical model calculations of the resonant,antenna-mediated local heating on a picosecond time scale.The hybrid,nanoscale excitation mechanism results in 20 times reduced switching energies and 5 times faster recovery times than a VO_(2) film without antennas,enabling fully reversible switching at over two million cycles per second and at local switching energies in the picojoule range.The hybrid solution of antennas and VO_(2) provides a conceptual framework to merge the field localization and phase-transition response,enabling precise,nanoscale optical memory functionalities. | Otto L Muskens Luca Bergamini Yudong Wang Jeffrey M Gaskell Nerea Zabala CH de Groot David W Sheel Javier Aizpurua | 2016 | Light(Science & Applications)2016，5，1： | 5 |
| 3 | New class of materials: half-metallic ferromagnets 显示文摘 | de Groot R A Muller F M van Engen P P M | 1983 | Phys Rev Lett1983，50，： | 2 |
| 4 | Magnetic and crystallographic properties of several C1b type Heusler compounds 显示文摘 | Helmholdt R B de Groot R A Mueller F M | 1984 | J Magn Magn Mater1984，43，： | 2 |
| 5 | Association of depression and diabetes complications: a meta analysis 显示文摘 | De Groot M Anderson R Freedland K | 2001 | Psychosom Med2001，63，： | 1 |
| 6 | Management of thyroid dysfunction during pregnancy and postpartum : an Endo- crine Society clinical practice guideline 显示文摘 | De Groot L Abalovich M Alexander EK | 2012 | J Clin Endocrinol Metab2012，97，8： | 1 |
| 7 | Genetic polymor- phisms related to the renin-angiotensin-aldosterone system and response to antihypertensive drugs显示文摘 | Taverne K de Groot M de Boer A | 2010 | Expert Opin Drug Metab Toxicol2010，6，4： | 1 |
| 8 | Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long- term survival显示文摘 | Humbert M Yaici A de Groote P | 2011 | Arthritis Rheum2011，63，11： | 1 |
| 9 | The Institution- al Determinants of Bilateral Trade Patterns 显示文摘 | De Groot H Linders G M Rietveld U | 2004 | Kyklos2004，57，1： | 1 |
| 10 | Coagulation disorders in septic shock 显示文摘 | Thijs L G de Boer J P de Groot M C | 1993 | Intensive Care Med1993，19，1： | 1 |
| 11 | A typology for the classification description and valuation of ecosystem functions, goods, and services 显示文摘 | DE GROOT R S WILSON M A BOUMANS R M J | 2002 | Ecological Economics2002，41，3： | 1 |
| 12 | The efficiency of nitrogen retention during compensatory growth of food-restricted broilers显示文摘 | Lippens M Huyghebaert G De Groote G | 2002 | Br Poult Sci2002，43，： | 1 |
| 13 | Meniscal tissue regeneration in porous 50/50 copoly(L-lactide/6-capralactone) implants显示文摘 | De Groot J H Zijlstra F M Kuijpers H W | 1997 | Biomaternals1997，18，8： | 1 |
| 14 | Body composition by dual energy X-ray absorptiometry in women with previous pre-eclampsia or small for gesta- tional age offspring 显示文摘 | BERENDS A L ZILLIKENS M C DE GROOT C J | 2009 | An International Journal of Ob- stetrics and Gynaecology2009，116，3： | 1 |
| 15 | Hypertension and cerebral white matter lesion in a prospective cohort study显示文摘 | De Leeuw FE de Groot JC Oudkerk M | 2002 | Brain2002，125，4： | 1 |
| 16 | Long-term follow-up after radiofrequency catheter ablation of ventricular tachycardia : a successful approach? 显示文摘 | Borger van der Burg A E de Groot N M van Erven L | 2002 | J Cardiovasc Electrophysiol2002，13，5： | 1 |
| 17 | Agrobacterium tumefaciens -mediated transformation of filamentous fungi 显示文摘 | de Groot M J A Bundock P Hooykaas P J J | 1998 | Nature Biotechnology1998，16，： | 1 |
| 18 | Designing better drugs: Predicting cytochreme P450 metabolism显示文摘 | de Groot M J | 2006 | Drug Discov Today2006，11，： | 1 |
| 19 | Apology for the classification, description and valuation of ecosystem functions显示文摘 | DE GROOT RS WILSON MA BOUMANS R M J | 2010 | Ecol Econ2010，41，： | 1 |
| 20 | Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites 显示文摘 | Ekins S de Groot M J Jones JP | 2001 | Drug Metab Dispos2001，29，： | 1 |
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