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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 | Review of the current targeted therapies for non-small-cell lung cancer显示文摘The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come. | Kim-Son H Nguyen Joel W Neal Heather Wakelee | 2014 | World Journal of Clinical Oncology2014，5，4： | 13 |
| 3 | Red River barrier and Pleistocene climatic fluctuations shaped the genetic structure of Microhyla fissipes complex (Anura: Microhylidae) in southern China and Indochina显示文摘 | Zhi-Yong YUAN Chatmongkon SUWANNAPOOM Fang YAN Nikolay A. POYARKOV JR Sang Ngoc NGUYEN Hong-man CHEN Siriwadee CHOMDEJ Robert W, MURPHY Jing CHE | 2016 | Current Zoology2016，62，6： | 11 |
| 4 | Renin and angiotensinogen expression and functions in growth and apoptosis of human glioblastoma显示文摘The expression and function in growth and apoptosis of the renin-angiotensin system(RAS)was evaluated inhuman glioblastoma.Renin and angiotensinogen(AGT)mRNAs and proteins were found by in situ hybridisationand immunohistochemistry in glioblastoma cells.Angiotensinogen was present in glioblastoma cystic fluids.Thus,human glioblastoma cells produce renin and AGT and secrete AGT.Human glioblastoma and glioblastoma cellsexpressed renin,AGT,renin receptor,AT(2)and/or AT(1)mRNAs and proteins determined by RT-PCR and/ | Juillerat-Jeanneret L Celerier J Chapuis Bernasconi C Nguyen G Wostl W Maerki HP Janzer RC Corvol P Gasc JM | 2004 | 中国神经肿瘤杂志2004，2，1： | 8 |
| 5 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 6 | 临床意义上的前列腺癌的预测标准化:可能吗?显示文摘近几十年来,对前列腺癌的生物学和流行病学的深入研究已经使前列腺癌的治疗取得了很大进展。很多前列腺癌可以在发病早期被发现,并且有多种有效的治疗手段。然而,仍无明确的数据表明这些早期诊断和治疗能够有效地控制前列腺癌的死亡率。这可能是由于接受治疗的一大部分癌症患者的恶性程度较低,即使不予治疗亦不会对患者的健康和生存期产生影响。基于过度治疗现象的存在,在当代的医疗过程中,积极监测以观后效被认为是一种有效的治疗方式。如何区别不具临床意义的肿瘤与高度恶性、高致死率的肿瘤,对为患者选择积极监测还是立即干预的治疗方案来说至关重要。本章节总结了风险分组和列线图等多种预测模型对于低度恶性肿瘤的预测能力及它们在局限性前列腺癌的治疗中所起的作用。 | Carver T Nguyen Michael W Kattan | 2012 | Asian Journal of Andrology2012，14，3： | 3 |
| 7 | Racial differences in effectiveness of α-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis显示文摘 | Mindie H Nguyen Ruel T Garcia Peter W Simpson Teresa L Wright Emmet B Keeffe | 2002 | Hepatology2002，，2： | 2 |
| 8 | Knowledge Acqui- sition and Performance of International Joint Ventures in the Transition Economy of Vietnam显示文摘 | Tsang E W K Nguyen D T Erramilli M K | 2004 | Journal of Information Mar-keting2004，12，2： | 1 |
| 9 | Random subspace two-dimensional PCA for face recognition显示文摘 | Nguyen N Liu W Venkates S | 2002 | Lecture notes in computer science2002，4810，： | 1 |
| 10 | Quorum sensing controls expression of the type Ⅲ secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli显示文摘 | Sperandio V Mellies JL Nguyen W | 1999 | Proc Natl Acad Sci USA1999，96，15： | 1 |
| 11 | Macrophage accumulation in human progressive diabetic nephropathy显示文摘 | Nguyen D Ping F Mu W | 2006 | Nephrology (Carlton)2006，11，3： | 1 |
| 12 | Laterally driven poly-silicon resonant microstructures 显示文摘 | Tang W C Nguyen Tu-Cuong H Howe R T | 1989 | Sensors and Actuators1989，20，12： | 1 |
| 13 | Oral N-carbamylglu- tamate supplementation inereases protein synthesis in skeletal muscle of piglets显示文摘 | Frank J W Escobar J Nguyen H V | 2007 | J Nutr2007，137，2： | 1 |
| 14 | Transcription factor PITX3 gene in Parkinson' s disease 显示文摘 | Le W Nguyen D Lin X W | 2011 | Neurobiol Aging2011，32，4： | 1 |
| 15 | A quintile regression decomposition urban-rural inequality in Vietnam 显示文摘 | NGUYEN B T ALBRECHT J W VROMAN S B | 2007 | Journal of Development Economics2007，，83： | 1 |
| 16 | Estradiol increases proliferation and down-regulates the sodium/iodide symporter gene in FRTL-5 cells显示文摘 | Furlanetto T W Nguyen L Q Jameson J L | 1999 | Endocrinology1999，140，12： | 1 |
| 17 | Intensity modulated radiotherapy for sinonasal malignancies with a focus on optic pathway preservation 显示文摘 | Chi A Nguyen 'NP Tse W | 2013 | J Hematol Oncol2013，6，： | 1 |
| 18 | Optical properties of porous silicon/poly(p phenylene vinylene) devices 显示文摘 | Nguyen T P Rendu P Cheah K W | 2003 | Physica E: Low-dimensional Systems and Nanostructures2003，17，： | 1 |
| 19 | Physically Based Modeling and Animation of Fire 显示文摘 | Nguyen D Q Ronald F Jensen H W | 2002 | ACM Transactions on Graphics2002，21，3： | 1 |
| 20 | Copulas and Markov processes显示文摘 | Darsow W Nguyen B Olsen E | 1992 | Illinois Journal of Mathematics1992，36，： | 1 |
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