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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 | Instantaneous frequency and wave mode identification in a magnetosheath using few spatial points显示文摘Observational data such as those obtained from the magnetosheath in the downstream of Earth's bow shock have waveforms that differ from those of sinusoidal signals. In practice, they are not even aggregates of sinusoidal signals. Therefore, the frequency decomposition for the data requires technique that will account for the time-varying features of the data that will lead to deduction of physical meaning of the observations. The combination of empirical mode decomposition (EMD) and Hilbert transform has been used for extracting the various contributing oscillatory modes (EMDs) and the instantaneous frequency determination (Hilbert transform) of every physically meaningful mode called intrinsic mode function (IMF). The resulting instantaneous frequencies are used to determine instantaneous wave vectors. The combination of the instantaneous frequencies and wave vectors is useful in the identification of wave modes based on the characteristics of the waves. The results show that EMD-Hilbert can be more reliable than simple Hilbert transform alone. | Nathaniel E U Beloff N George N J | 2013 | Chinese Physics B2013，22，8： | 2 |
| 3 | Water and nutrient translocation by hyphae of Glomus mosseae显示文摘 | George E Haussler K U Vetterlein D | 1992 | Can J Bot1992，70，： | 1 |
| 4 | Malignant granular cell tumor of the tongue:a clinico-pathological challenge显示文摘 | Krishnamurthy A George R Maihi U | 2014 | Indian J Surg Oncol2014，5，1： | 1 |
| 5 | Effectiveness of vendor - managed inventory in the electronics industry:determinants and outcomes 显示文摘 | GEORGE K U K | 2004 | Information & Management2004，，41： | 1 |
| 6 | Treatment planning com-parison of conventional, 3D eonformal, and intensity- mod -ulated photon(IMRT) and proton therapy for paranasal sinus eareinoma 显示文摘 | Mock U Georg D Bogner J | 2004 | Int J Radiat Oneol Biol Phys2004，58，1： | 1 |
| 7 | 显示文摘 | Suresha S N Georg V Shankar A U R | 2010 | Materials and Structures2010，43，6： | 1 |
| 8 | Lupus erythematosus tumidus 显示文摘 | Pakran J George M Rajan U | 2011 | Indian J Dermatol Venereol Leprol2011，77，2： | 1 |
| 9 | IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy 显示文摘 | Suppiah V Moldovan M Ahlenstiel G Berg T Weltman M Abate ML Bassendine M Spengler U Dote GJ Powell E Riordan S Sheridan D Smedile A Fragomeli V Muller T Bahlo M Stewart GJ Booth DR George J | 2009 | Nat Genet2009，41，10： | 1 |
| 10 | Treatment planning comparison of conventional,3D conformal,and intensity-modulated photon(IMRT)and proton therapy for paranasal sinus carcinoma显示文摘 | Mock U Georg D Bogner J | 2004 | Int J Radiat Oncol Biol Phys2004，58，1： | 1 |
| 11 | IL28Bis associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy显示文摘 | Suppiah V Moldovan M Ahlenstiel G Berg T Weltman M Abate ML Bassendine M Spengler U Dore GJ Powell E Riordan S Sheridan D Smedile A Fragomeli V Müller T Bahlo M Stewart GJ Booth DR George J | 2009 | Nat Genet2009，41，10： | 1 |
| 12 | Improved HPLC method for the simultaneous determination of allantoin,uric acid and creatinine in cattle urine显示文摘 | GEORGE S K DIPU M T MEHRA U R | 2006 | J Chromatogr B2006，832，： | 1 |
| 13 | Validation of turbulence closure parameterizations for stably stratified flows using the PROVESS turbulence measurements in north sea 显示文摘 | PATRICK J L SANDRO C GEORG U | 2002 | Journal of Sea Research2002，47，3： | 1 |
| 14 | Influences on breast cancer screening behaviors in Tamil immigrant women 50 years old and over显示文摘 | Meana M Bunston T George U | 2001 | Ethn Health2001，6，34： | 1 |
| 15 | Preparation and Characterisation of nano-structured WO3-TiO2 layers for photoelectrochromic devices 显示文摘 | Krasovec U Topic M Georg A | 2005 | Journal of Sol-Gel Science and Technology2005，36，： | 1 |
| 16 | Genetic diversity of soybean cultivars from China, Japan, North America, and north America ancestral lines determined by amplified fragment length polymorphism 显示文摘 | George N U Kenworthy W J Costa J M | 2003 | Crop sci2003，43，： | 1 |
| 17 | A needs- based model for settlement service delivery for newcomers to Canada 显示文摘 | GEORGE U | 2002 | International Social Work2002，45，4： | 1 |
| 18 | Continuous venovenous hemofiltration improves arterial oxygenation in endotoxin-induced lung injury in pigs显示文摘 | Roman U Georg R Christine L | 2002 | Anesthesiology2002，95，2： | 1 |
| 19 | Treatment planning comparison of conventional, 3D conformal, and intensity - modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma 显示文摘 | Mock U Georg D Bogner J | 2004 | Int J Radiat Oncol Biol Phys2004，58，： | 1 |
| 20 | Growth of crossbred bulls affected by level of feed in- take显示文摘 | GEORGE S K DIPU M T MEHRA U R | 2005 | Indian Journal Animal Nutrition2005，22，2： | 1 |
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