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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 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 3 | Durability of Radiofrequency Ablation in Barrett’s Esophagus With Dysplasia显示文摘 | Nicholas J. Shaheen Bergein F. Overholt Richard E. Sampliner Herbert C. Wolfsen Kenneth K. Wang David E. Fleischer Virender K. Sharma Glenn M. Eisen M. Brian Fennerty John G. Hunter Mary P. Bronner John R. Goldblum Ana E. Bennett Hiroshi Mashimo Richard I | 2011 | Gastroenterology2011，，2： | 3 |
| 4 | 多途径丝裂原激活的蛋白激酶介导一氧化氮引起的肝癌细胞凋亡显示文摘目的 研究非离子型的diazeniumdiolate类一氧化氮供体引起肝癌细胞凋亡的分子机制。方法 利用免疫印迹、免疫沉淀、凝胶阻滞实验研究一氧化氮供体处理Hep3B肝癌细胞后,丝裂原激活的蛋白激酶、AP-1的激活以及和Hep3B肝癌细胞凋亡的关系。结果 一氧化氮可引起细胞外信号调节蛋白激酶、c-jun N末端激酶和p38激酶的激活,特别是细胞外信号调节的蛋白激酶的持续激活,其中细胞外信号调节的蛋白激酶和c-jun N末端激酶的特异的阻断剂U0126和JNK抑制剂Ⅱ可阻断AP-1的激活和Hep3B细胞的凋亡,而p38激酶的阻断剂SB203580不能阻断AP-1的激活和Hep3B肝癌细胞的凋亡。结论 一氧化氮通过激活细胞外信号调节蛋白激酶、c-jun N末端激酶,进而激活AP-1而引起Hep3B肝癌细胞的凋亡。 | 任正刚 刘银坤 Ziqiu Wang Sid Kar Brian I Carr | 2004 | 肿瘤2004，24，5： | 3 |
| 5 | Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients显示文摘 | Antonio Facciorusso Valentina Del Prete Nicola Crucinio Nicola Muscatiello Brian I Carr Alfredo Di Leo Michele Barone | 2015 | J Gastroenterol Hepatol2015，，11： | 2 |
| 6 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet . 2011 (9807)2011，，9807： | 2 |
| 7 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet2011，，9807： | 2 |
| 8 | Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study显示文摘 | Olivier Rixe Ronald M Bukowski M Dror Michaelson George Wilding Gary R Hudes Oliver Bolte Robert J Motzer Paul Bycott Katherine F Liau James Freddo Peter C Trask Sinil Kim Brian I Rini | 2007 | Lancet Oncology2007，，： | 2 |
| 9 | Renal cell carcinoma显示文摘 | Brian I Rini Steven C Campbell Bernard Escudier | 2009 | The Lancet2009，，9669： | 1 |
| 10 | Anisotropy correction for devlated-well sonic logs: application to seismic well tie显示文摘 | Brian E H John M H Donald W I | 2003 | Geophysics2003，68，2： | 1 |
| 11 | The critical periedsfor weed control in white beans显示文摘 | Brian I W Thomas E M Michael R H | 1999 | Weed Science1999，41，： | 1 |
| 12 | Evalution of the molecular epidemiology of an outbreak of multiple resistant Shigella sonnei in a day care center by using pulsed-field gel dec trophoresis and plasmid DNA analysis 显示文摘 | Brian M J Van R Townsend I | 1993 | J Clin Mierobiol1993，31，8： | 1 |
| 13 | Sinusoidal Modeling and Adaptive Channel Prediction in Mobile OFDM Systems显示文摘 | Wong I C Brian L E | 2008 | IEEE Trans on Signal Processing2008，56，4： | 1 |
| 14 | The Critical periods for weed control in white beans显示文摘 | BRIAN I W THOMAS E M MICHAEL R H | 1999 | Weed Science1999，41，： | 1 |
| 15 | Imaging internal multiples from subsalt VSP data-Examples of target-oriented interferometry显示文摘 | Vasconcelos I Snieder R Brian Hornby B | 2008 | Geophysics2008，73，4： | 1 |
| 16 | The control of rotting and browning of litchi fruit by hot benomyl and plastic film 显示文摘 | Kevin J S Brian I B Grantley R C | 1982 | Scientia Horticalture1982，16，3： | 1 |
| 17 | Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization显示文摘AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P < 0.017) and 0.99(95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P < 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P < 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI. | Yossi Ventura Brian I Carr Issac Kori Vito Guerra Oren Shibolet | 2018 | World Journal of Gastroenterology2018，24，15： | 1 |
| 18 | High pressure routes todimethyl carbonate from supercritical carbon dioxide显示文摘 | Neil S I Brian O Carla V | 1999 | Tetrahedron1999，55，11： | 1 |
| 19 | Evaluation of the molecular epidemiology of an outbreak of multiply resistant Shigella sonnei in a day care center by using PFGE and plasmid DNA analysis显示文摘 | Brian M J Van R Townsend I | 1993 | J Clin Microbiol1993，31，8： | 1 |
| 20 | Revised fire consequence models for offshore quantitative risk assessment 显示文摘 | Ravichandra Pulaa Faisal I Khana Brian Veitcha | 2005 | Journal of Loss Prevention in the Process Industries2005，18，： | 1 |
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