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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 | Proposed approach to the challenging management of progressive gastroesophageal reflux disease显示文摘The progression of gastroesophageal reflux disease(GERD) in patients who are taking proton pump inhibitors(PPIs) has been reported by several investigators,leading to concerns that PPI therapy does not address all aspects of the disease.Patients who are at risk of progression need to be identified early in the course of their disease in order to receive preventive treatment.A review of the literature on GERD progression to Barrett's esophagus and the associated physiological and pathological changes was performed and risk factors for progression were identified.In addition,a potential approach to the prevention of progression is discussed.Current evidence shows that GERD can progress;however,patients at risk of progression may not be identified early enough for it to be prevented.Biopsies of the squamocolumnar junction that show microscopic intestinalization of metaplastic cardiac mucosa in endoscopically normal patients are predictive of future visible Barrett's esophagus,and an indicator of GERD progression.Such changes can be identified only through biopsy,which is not currently recommended for endoscopically normal patients.GERD treatment should aim to prevent progression.We propose that endoscopically normal patients who partially respond or do not respond to PPI therapy undergo routine biopsies at the squamocolumnar junction to identify histological changes that may predict future progression.This will allow earlier intervention,aimed at preventing Barrett's esophagus. | Joachim Labenz Parakrama T Chandrasoma Laura J Knapp Tom R DeMeester | 2018 | World Journal of Gastrointestinal Endoscopy2018，10，9： | 7 |
| 3 | Inflammation and Alzheimer’s disease显示文摘 | Haruhiko Akiyama Steven Barger Scott Barnum Bonnie Bradt Joachim Bauer Greg M Cole Neil R Cooper Piet Eikelenboom Mark Emmerling Berndt L Fiebich Caleb E Finch Sally Frautschy W.S.T Griffin Harald Hampel Michael Hull Gary Landreth Lih–Fen Lue Robert Mrak | 2000 | Neurobiology of Aging2000，，3： | 2 |
| 4 | Stellenwert der Kipptischuntersuchung im Vergleich zum Schellong-Test bei orthostaseinduzierten Kreislaufdysregulationen/Synkopen显示文摘 | Sven Jungblut* Hagen Frickmann* Albrecht R?mer Hans Joachim Gilfrich | 2006 | Medizinische Klinik2006，，3： | 2 |
| 5 | Multiweight optimization in optimal bounding ellipsoid algorithms 显示文摘 | JOACHIM D DELLER J R | 2006 | IEEE Transactions on Signal Processing2006，54，： | 1 |
| 6 | RF-superimposed DC and pulsed DC sputte- ring for deposition of transparent conductive ox- ides显示文摘 | MICHAEL S JOACHIM M MANFRED R | 2007 | Thin Solid Films2007，515，19： | 1 |
| 7 | Depletion of CD8+cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2cytokine profile显示文摘 | Blois SM Joachim R Kandil J | 2004 | J Immunol2004，172，： | 1 |
| 8 | Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic perfusion imaging显示文摘 | Joachim R Lars J Anke F | 2000 | Arch Neurol2000，57，： | 1 |
| 9 | Ultrastructural organization and micromechanical properties of shark tooth enameloid显示文摘 | Joachim E Anna M J Dierk R | 2014 | Acta Biomaterialia2014，10，9： | 1 |
| 10 | Structure, composition, and mechanical properties of shark teeth显示文摘 | Joachim E Oleg P Dierk R | 2012 | Journal of Structural Biology2012，178，3： | 1 |
| 11 | Prediction and assessment of the effects of mixtures of four xenoestrogens 显示文摘 | Joachim P Nissanka R Megan W | 2000 | Environ Health Perspect2000，108，： | 1 |
| 12 | Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis:a double-blind,randomized,multicentre trial显示文摘 | JOSEF S SMOLEN JOACHIM R KALDEN DAVID L SCOTT | 1999 | The Lancet1999，23，353： | 1 |
| 13 | Metabolic design based on a coupled gene expression-metabolic network model of tryptophan production in Escherichia coli显示文摘 | Joachim WS Klaus M Matthias R | 2004 | Metabolic Engineering2004，6，： | 1 |
| 14 | Antipyresis caused by stimulation of vasopressinergic neurons and intraseptal or systemic in fusions of γ-MSH显示文摘 | Matthias B Joachim R Matthew JK | 1994 | Am J Physiol1994，，： | 1 |
| 15 | The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response 显示文摘 | Joachim R Zenelussen AC Polgar B | 2003 | Steroids2003，68，10111213： | 1 |
| 16 | Influence of imidazole replacement in different structural classes of histamine H-receptor antagonists 显示文摘 | Galina M Joachim A Ulrich R | 2001 | Eur J Pharm Sei2001，13，3： | 1 |
| 17 | Tomographic imaging inthe diag- nosis of pulmonary embolism: a comparison between V/Q lung scintigraphy in SPEC'T technique and Multislice Spiral CT显示文摘 | Patrich R Joachim EW | 2004 | Journal of Nuclear Medicine2004，45，： | 1 |
| 18 | A systematic review and meta analysis of the effects of'clinical pathways on length of stay, hospital costs and pa- tient outcomes 显示文摘 | Thomas R Joachim K Rainer K | 2008 | BMC Health Services Research2008，8，： | 1 |
| 19 | Depletion of CD8 + cells abolishes the pregnancy protective effect of progesterone substitution with dydroogesterone in mice by altering the Thl/Th2 cytokine profile 显示文摘 | Blois SM Joachim R Kandil J | 2004 | J Immunol2004，172，10： | 1 |
| 20 | The progesterone derivative dydrogesterone abrogates murine stress-triggered abortion by inducing a Th2 biased local immune response显示文摘 | Joachim R Zenclussen A C Polgar B | 2003 | Steriods2003，68，1013： | 1 |
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