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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 | Ever-increasing diversity of drug-induced pancreatitis显示文摘With over 100000 hospital admissions per annum,acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has farreaching impact well beyond.It has become increasingly recognized that druginduced pancreatitis(DIP),despite accounting for less than 3%of all cases,represents an important and growing though often inconspicuous cause of acute pancreatitis.Nevertheless,knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents,especially for nonprescription medications.Indeed,the majority of available data is derived from case reports,case series,or case control studies.Furthermore,the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established(<10%of cases).Several classification systems have been proposed,but no single system has been widely adopted,and periodic updates are required in light of ongoing pharmacologic expansion.Moreover,infrequently prescribed medications or those available over-thecounter(including herbal and other alternative remedies)are often overlooked as a potential culprit of acute pancreatitis.Herein,we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity.We believe this manuscript will aid in increasing both primary and secondary prevention of DIP,thus ultimately facilitating more expedient diagnosis and a decrease in DIPrelated morbidity. | Simcha Weissman Muhammad Aziz Ryan B Perumpail Tej I Mehta Rutwik Patel James H Tabibian | 2020 | World Journal of Gastroenterology2020，26，22： | 8 |
| 3 | Rho GTPase activation is a key step in renal epithelial mesenchymal transdifferentiation 显示文摘 | PATEL S TAKAGI K I SUZUKI J | 2005 | JAm Soc Nephrol2005，16，7： | 1 |
| 4 | Gastrointes- tinal hormonal responses on GPR119 activation in lean and diseased rodent models of type 2 diabetes 显示文摘 | PATEL S MACE O J TOUGH I R | 2014 | In- ternational Journal of Obesity2014，38，10： | 1 |
| 5 | The enzymatic cycliza- tion of nerolidyl diphosphate by δ-cadinene synthase from cotton stele tissue infected with Verticillium dahliae 显示文摘 | Alchanati I Patel J Liu J | 1998 | Phytochemistry1998，47，6： | 1 |
| 6 | Reducing OWL entailment to description logic satisfiability显示文摘 | HORROCKS I PATEL SCHNEIDER P F | 2004 | Journal of Web Semantics2004，1，4： | 1 |
| 7 | Axillary lymph node metastasis from an occult beast cancer显示文摘 | Patel I Nemoto T Rosner D | 1981 | Cancer1981，47，12： | 1 |
| 8 | Metabolomic approach for the detection of mechanically recovered meat in food products 显示文摘 | Surowiec I Fraser PO Patel R | 2011 | Food Chemistry2011，125，4： | 1 |
| 9 | Genome size is a strong predictor of cell size and stomatal density in angio- sperms 显示文摘 | Beaulieu J M Leitch I J Patel S | 2008 | New Phytologist2008，179，： | 1 |
| 10 | Bronchiectasis,exacerbation indices,and inflammation in chronic obstructivepulmonary disease 显示文摘 | Patel IS Vlahos I Wilkinson TM | 2004 | Am J Respir Crit Care Med2004，170，： | 1 |
| 11 | The role of TGF~ signaling in wound epithelialization显示文摘 | Ramirez H Patel SB Pastar I | 2014 | Adv Wound Care2014，3，7： | 1 |
| 12 | Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans 显示文摘 | Al Mheid I Patel R Murrow J | 2011 | J Am Coll Cardiol2011，58，： | 1 |
| 13 | Water-soluble Ag nano- clusters exhibit strong two-photon-induced fluorescence 显示文摘 | PATEL S A RICHARDS C I HSIANG J C | | J Am Chem Soc0，130，11： | 1 |
| 14 | Equipment-related electrocardiograp-hic artifacts: causes, characteristics, consequences,and cor-rection显示文摘 | Patel S I Souter M J | 2008 | Anesthesiology2008，108，1： | 1 |
| 15 | Utility of postoperative CEA for surveillance of recurrence after resection of primary colorectal cancer显示文摘 | Bhatti I Patel M Dennison AR | 2015 | Int J Surg2015，，： | 1 |
| 16 | Enantioselective enzymatic acylation of 1-(3-bromophenyl)ethylamine显示文摘 | Gill I I Das J Patel R N | 2007 | Tetrahedron: Asymmetry2007，18，： | 1 |
| 17 | Resistin is expressed in human macrophages and directly by PPAR gamma activators显示文摘 | PATEL L BUCKELS A C KINGHOM I J | 2003 | Biochem Biophys Res Commun2003，300，： | 1 |
| 18 | Herpes simplex type l induction of persistent NF-kappa B nuclear translocation increases the efficiency of virus replication 显示文摘 | Patel A Hanson J McLean T I | 1998 | Virology1998，247，2： | 1 |
| 19 | Peripheral and central measurements of bone mineral density are equal y strongly associated with clinical risk factors for osteoporosis显示文摘 | Patel R Black GM Fogelman I | | 0，，02： | 1 |
| 20 | Radio{re- quency ablation (coblation): a promising new tech- nique {or laryngeal papillomata显示文摘 | TIMMS M S BRUCE I A PATEL N K | 2007 | J Laryngol Otol2007，121，： | 1 |
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