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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 | Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis显示文摘AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course. | Animesh Jain Evan J Lipson William H Sharfman Steven R Brant Mark G Lazarev | 2017 | World Journal of Gastroenterology2017，23，11： | 8 |
| 3 | Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-1igase signaling effector DWARF3显示文摘 | Li-Hua Zhao X Edward Zhou Wei Yi Zhongshan Wu Yue Liu Yanyong Kang Li Hou Parker W de Waal Suling Li Yi Jiang Adrian Scaffidi Gavin R Flematti Steven M Smith Vinh Q Lam Patrick R Griffin YonghongWang Jiayang Li Karsten Melcher H Eric Xu | 2015 | Cell Research2015，25，11： | 7 |
| 4 | Shoot and root traits in drought tolerant maize(Zea mays L.) hybrids显示文摘This study aimed to investigate the differences in shoot and root traits, and water use and water use efficiency(WUE) in drought tolerant(DT) maize(Zea mays L.) hybrids under full and deficit irrigated conditions. A two-year greenhouse study was conducted with four hybrids(one conventional hybrid, 33D53AM, two commercial DT hybrids, P1151 AM, N75H, and an experimental hybrid, Exp HB) grown under two water regimes(I_(100) and I_(50), referring to 100 and 50% of evapotranspiration requirements). Under water stress, the hybids P1151 AM, N75, and Exp HB showed more drought tolerance and had either greater shoot dry weight or less dry weight reduction than the conventional hybrid(33 D53 AM). However, these three hybrids responded to water stress using different mechanisms. Compared with the conventional hybrid, the two commercial DT hybrids(P1151 AM and N75H) had a smaller leaf area, shoot dry weight, and root system per plant. As a result, these hybrids used less water but had a higher WUE compared with the conventional hybrid. In contrast, the experimental hybrid(ExpHB) produced more shoot biomass by silking stage at both irrigation levels than all other hybrids, but it had relatively lower WUE. The hybrids demonstrated different drought response mechanisms that may require different irrigation management strategies. More investigation and validation are needed under field conditions and in different soil types. | ZHAO Jin XUE Qing-wu Kirk E Jessup HOU Xiao-bo HAO Bao-zhen Thomas H Marek XU Wen-wei Steven R Evett Susan A O'Shaughnessy David K Brauer | 2018 | Journal of Integrative Agriculture2018，17，5： | 3 |
| 5 | Phenotypic instability and rapid gene silencing in newly formed Arabidopsis alloteraploids显示文摘 | Comai L Tyagi A P Winter K Holmes-Davis R Reynolds S H Stevens Y Byers B | 2000 | Plant Cell2000，12，9： | 2 |
| 6 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 7 | A Unified Log-based Relevance Feedback Scheme for Image Retrieval显示文摘 | Steven C H Michael H R | 2006 | IEEE Transactions on Knowledge and Data Engineering2006，18，4： | 1 |
| 8 | Work,family and health:the expanding role of EAP professionals显示文摘 | BEACH R H STEVEN MARTIN K JACK | 1995 | Employee Counselling Today1995，7，4： | 1 |
| 9 | Pitting of a glass-ceramic during polishing with cerium oxide显示文摘 | SABIA R STEVENS H J VARNER J R | | 0，，： | 1 |
| 10 | Effect of bromide ion on formation of haas during chlorination 显示文摘 | Pourmoghaddas H Stevens A A Kinman R N | 1993 | J Am Water Works Ass1993，85，1： | 1 |
| 11 | Clinical guidelines Potential benefits, limitations, and harms of clinical guidelines显示文摘 | Steven H Woolf Grol R Hutchinson A | 1999 | BMJ1999，318，7182： | 1 |
| 12 | The empirical mode decomposition and the Hilbert spectrum for nonlinear and non-stationary time series analysis显示文摘 | Norden E H Zheng Shen Steven R Long | 1998 | Mathematical Physical and Engineering Sciences1998，454，1971： | 1 |
| 13 | Layering as Optimization Decomposition: A Mathematical Theory of Network Architectures 显示文摘 | Mung C Steven H L Calderbank R A | 2007 | Proceedings of IEEE2007，95，1： | 1 |
| 14 | Regulation of Retinal Cone Bipolar Cell Differentiation and Photopic Vision by the CVC Homeobox Gene Vsx1显示文摘 | Akihira Ohtoshi Steven W Wang Hidetaka Maeda Shannon M Saszik Laura J Frishman William H Klein Richard R Behringer | 2004 | Current Biology2004，，6： | 1 |
| 15 | Synthesis of alumina from high purity alum derived from coal fly ash显示文摘 | Park H C Park Y J Stevens R | 2004 | Materials Science and Engineering A2004，367，12： | 1 |
| 16 | Effects of CO2 gas as leaks from geological storage sites on agro-ecosystems显示文摘 | Patil R H Colls J J Steven M D | 2010 | Energy2010，35，12： | 1 |
| 17 | Preoperative lower esophageal sphincter pressure affects outcome of laparoscopic esophageal myotomy for achalasia显示文摘 | Mustafa A Arain Jeffrey H Peters Anan P Tamhankar Giuseppe Portale Gideon Almogy Steven R DeMeester Peter F Crookes Jeffrey A Hagen Cedric G Bremner Tom R DeMeester | 2004 | Journal of Gastrointestinal Surgery2004，，3： | 1 |
| 18 | Effect of the novel anxiolytic drug deramciclane on cytochrome P450 2D6 activity as measured by desipramine pharmacokinetics显示文摘 | Kari L Steven DB Harry B Juha R Jutta H Harry S | 2004 | Eur J Clin Pharmacol2004，59，： | 1 |
| 19 | Gill morphometry in growth hormone transgenic Pacific coho salmon, Oncorhynchus kisutch 显示文摘 | Stevens E D Devlin R H | 2000 | Environ Biol Fish2000，58，： | 1 |
| 20 | How to measure an organization's learning ability:The facilitating factors-Part Ⅱ显示文摘 | WALTER R | 1998 | Journal of Workplace Learning1998，10，1： | 1 |
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