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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 | Management of water resources for quality and quantity 显示文摘 | Vijayan G Nathan N S Subramanian R S | 1999 | Journal of Indian Water Works Association1999，，： | 2 |
| 3 | Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. | Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni | 2016 | World Journal of Hepatology2016，8，23： | 2 |
| 4 | Appendectomy and Clostridium difficile colitis:Relationships revealed by clinical observations and immunology显示文摘Advances in understanding the interaction between the human immune system and the microbiome have led to an improved understanding of the function of the vermiform appendix as a safe-house for beneficial bacteria in the colon.These advances have been made despite long standing clinical observations that the appendectomy is a safe and effective procedure.However,more recent clinical data show that an appendectomy puts patients at increased risk for recurrent Clostridium difficile(C.difficile)-associated colitis,and probably other diseases associated with an altered microbiome.At the same time,appendectomy does not apparently put patients at risk for an initial onset of C.difficile-associated colitis.These clinical observations point toward the idea that the vermiform appendix might not effectively protect the microbiome in the face of broad spectrum antibiotics,the use of which precedes the initial onset of C.difficile-associated colitis.Further,these observations point to the idea that historically important threats to the microbiome such as infectious gastrointestinal pathogens have been supplanted by other threats,particularly the use of broad spectrum antibiotics. | Nathan L Sanders R Randal Bollinger Ryan Lee Steven Thomas William Parker | 2013 | World Journal of Gastroenterology2013，19，34： | 2 |
| 5 | ADA与EASD对2型糖尿病高血糖处理:治疗启动与评定的新共识方案显示文摘在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于'2型糖尿病高血糖处理的共识声明'同时发表在2008年1月和12月的《Diabetes Care》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载(参阅《中国糖尿病杂志》2008年第7期)。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。 | Nathan DM Buse JB Davidson MB Ferrannini E Holman RR Sherwin R Zinman B 钱荣立(摘译) | 2009 | 中国糖尿病杂志2009，17，1： | 2 |
| 6 | Giant cell tumor显示文摘 | Daffner R H Nathan G Buterbauch G A | 1994 | Skeletal Radiol1994，23，3： | 1 |
| 7 | Spectral-Domain covariance estimation with a priori knowledge 显示文摘 | PRASHANTH R G NATHAN A G | 2006 | IEEE Transactions on Aerospace and Electronic system2006，42，3： | 1 |
| 8 | Long-distance dispersal of plants 显示文摘 | Nathan R | 2006 | Science2006，313，： | 1 |
| 9 | Mechanisms of long-distance seed dispersal显示文摘 | Nathan R Schurr F M Spiegel O | 2008 | Trends in Ecology and Evolution2008，23，： | 1 |
| 10 | Regulation of microtubule stability and mitotic progression by survivin显示文摘 | Alessandra Giodini Marko JK Nathan R | 2002 | Cancer Research2002，62，9： | 1 |
| 11 | The burden of allergic rhinitis显示文摘 | NATHAN R A | 2007 | Allergy Asthma Proc2007，28，： | 1 |
| 12 | Hiring for the Organization, Not the Job显示文摘 | Bowen D E Ledford G E Jr Nathan B R | 1991 | Ademy of Management Executive1991，5，4： | 1 |
| 13 | Evaluation of automated techniques for base flow and recession analysis显示文摘 | Nathan R J McMahon T A | 1990 | Water Resources Research1990，26，7： | 1 |
| 14 | Phase Ⅱ trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer显示文摘 | Hudes G R Nathan F Khater C | 1997 | J Clin Oncol1997，15，： | 1 |
| 15 | Spectral comparisons of coniferyl and cinnamyl alcohol epoxide derivatives with a purported cis-epoxyconiferyl alcohol isolate 显示文摘 | Nathan R Guz R Frank S | 2000 | Phytochemistry2000，54，8： | 1 |
| 16 | Emergency neurologic life support: meningitis and encephalitis 显示文摘 | Gaieski D F Nathan B R Weingart S D | 2012 | Neurocrit Care2012，17，01： | 1 |
| 17 | Self-oriented regular arrays of carbon nanotubes and their field emission properties 显示文摘 | Michael G Chapline Nathan R Franhlin | 1999 | Science1999，283，22： | 1 |
| 18 | Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo显示文摘 | Rervin S Singh R | 1999 | Circ Res1999，20，： | 1 |
| 19 | Hiring for the organization not the job显示文摘 | Bowen D E Ledford G E Jr Nathan B R | 1991 | Academy of Management Executive1991，5，： | 1 |
| 20 | Development of the asthma control test:a survey for assessing asthma control显示文摘 | Nathan R A Sorkness C A Kosinski M | 2004 | J Allergy Clin Immunol2004，113，1： | 1 |
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