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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 | STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer显示文摘Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC. | Andrew V Nguyen Yuan-Yuan Wu Elaine Y Lin | 2014 | World Journal of Gastroenterology2014，20，30： | 7 |
| 3 | Laparoscopic resection of gastrointestinal stromal tumors:Does laparoscopic surgery provide an adequate oncologic resection?显示文摘Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract.Surgical resection remains the mainstay of non-metastatic disease.However,the ability to provide an adequate oncologic resection using laparoscopic surgery is still an area of debate.This is a thorough review of the current literature,looking particularly at the use of laparoscopic surgery for larger GISTs and the long-term oncologic outcomes compared to the results of open surgery.Laparoscopic resections provide an adequate oncologic result for GISTs of all sizes,including those greater than 5 cm in size. | Joseph J Kim James Y Lim Scott Q Nguyen | 2017 | World Journal of Gastrointestinal Endoscopy2017，9，9： | 3 |
| 4 | Effects of high-temperature annealing on the dielectric function of Ta2O5 films observed by spectroscopic eUipsometry 显示文摘 | Nguyen N V Richter C A Cho Y J | 2000 | Applied Physics Letters2000，77，： | 1 |
| 5 | The design of a piezostack-based active mount and application to a vibration control system 显示文摘 | Nguyen V Q Choi S M Han Y M | 2008 | Smart Materials and Structures2008，17，06： | 1 |
| 6 | Use of granules of biphasie ceramic in rehabilitation of canal wall down mastoidecto- my显示文摘 | Bemardesehi D Nguyen Y Mosnier I | 2014 | Eur Arch Otorhinolaryngol2014，271，1： | 1 |
| 7 | Catalytic diesel particulate filter显示文摘 | Y Nguyen Huu Nhon H Mohamed Magan C Petit | 2003 | Applied Catalysis B, Environmental2003，，2： | 1 |
| 8 | Inhibition ofCD4+ CD25+ regulatory T-cell function by calcineurindependentinterleukin-2 production 显示文摘 | ZEISER R NGUYEN Y H BEILHACK A | 2006 | Blood2006，108，1： | 1 |
| 9 | Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat显示文摘 | Qiu Y Nguyen KD Odegaard JI | 2014 | Cell2014，157，6： | 1 |
| 10 | Correlation Between Microstructure and the Optical Properties of TiO2Thin Films Prepared on Different Substrates显示文摘 | Leprince W Y Yu Z K Nguyen V et a1 | 1997 | Thin So1id Films1997，307，12： | 1 |
| 11 | A Meta Analysis of the Antecedents and Conse- quences of Pay Level Satisfaction 显示文摘 | WILLIAMS M L MCDANIEL M A NGUYEN N Y | 2006 | Journal of Applied Psychology2006，91，2： | 1 |
| 12 | Neuraminidase inhibitor sus- ceptibility testing of influenza type B viruses in China during 2010 and 2011 identifies viruses with reduced susceptibility to oseltamivir and zanamivir显示文摘 | Wang D Sleeman K Huang W Nguyen H T LevineM Cheng Y Li X Tan M Xing X Xu X Klimov A I Gubareva L V Shu Y | 2013 | Antiviral Research2013，97，3： | 1 |
| 13 | On the strength of the hydrogen carbon Interaction as deduced from physisorption显示文摘 | NGUYEN T X BAE J S WANG Y | 2009 | Langmuir2009，25，8： | 1 |
| 14 | Electrophysiological recording of deep tendon reflexes:normative data in children and in adults显示文摘 | Pereon Y Nguyen The Tich S Fournier E | 2004 | Neurophysiol Clin2004，34，34： | 1 |
| 15 | The influence of long-rangetransport on atmospheric mercury on Jeju Island,Korea 显示文摘 | Nguyen H T Kim M Y Kim K H | 2010 | Science of the Total Environment2010，408，6： | 1 |
| 16 | Geometry optimization of MR valves constrained in a specific volume using the finite element method 显示文摘 | NGUYEN Q H HAN Y M CHOI S B | 2007 | Smart Materials and Structures2007，16，6： | 1 |
| 17 | 显示文摘 | Nguyen V K Yoo Y | 2006 | Sensors and Actuators B2006，13，： | 1 |
| 18 | Multiresolution image representation using combined 2-D and 1-D directional filter banks显示文摘 | Tanaka Y Ikehara M Nguyen T Q | 2009 | IEEE Transactions on Image Processing2009，18，2： | 1 |
| 19 | N-cadherin expression is in- volved in malignant behavior of head and neck cancer in relation to epithelial-mesenchymal transition显示文摘 | P T Nguyen Y Kudo M Yoshida | 2011 | Histology and Histopathology2011，26，2： | 1 |
| 20 | Mass mortali- ty of cultured sevenband grouper, Epinephelus septernfascia- tus, associated with viral nervous necrosis 显示文摘 | Fukuda Y Nguyen H D Furuhashi M | 1996 | Fish Patholo- gy1996，31，3： | 1 |
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