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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 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 3 | It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis. | Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators | 2019 | Stroke & Vascular Neurology2019，4，1： | 6 |
| 4 | Preparation and properties of plasticized starch modified with poly(ε-caprolactone) based waterborne polyurethane显示文摘 | CAO XIAO-DONG CHANG P R HUNEAULT M A | 2008 | Carbohydrate Polymers2008，71，1： | 1 |
| 5 | Northwestward-propagating wave patterns over the tropical western North Pacific during summer显示文摘 | CHANG C-P CHEN J M HARR P A | 1996 | Mon Wea Rev1996，124，： | 1 |
| 6 | Corner sequence-a P admissible floorplan representation with a worst case linear-time packing scheme 显示文摘 | Lin J M Chang Y W Lin S P | 2003 | IEEE Transactions on Very Large Integration Systems2003，11，4： | 1 |
| 7 | Influence of tyre loading and inflation pressure on standing显示文摘 | Chang Y P Gindy M E Streit D A | 2003 | Heavy Ve- hicle Systems2003，10，： | 1 |
| 8 | Identification and subtyping of avian influenza viruses by reverse tran-scription-PCR 显示文摘 | Lee M S Chang P C Shien J H | 2001 | J Virol Methods2001，97，12： | 1 |
| 9 | NF-kap-paB-dependent induction of microRNA miR-146,an in-hibitor targeted to signaling proteins of innate immune re-sponses显示文摘 | Taganov K D Boldin M P Chang K J | 2006 | Proc Natl Acad Sci U S A2006，103，12： | 1 |
| 10 | Material and electrical characterization of carbon-doped Ta2O5 films for embedded dynamic random access memory applications显示文摘 | Chu K Chang J P Steigerwald M L | 2002 | Journal of Applied Physics2002，91，1： | 1 |
| 11 | Synthesis of large surface area carbon xerogels for electrochemical double layer capacitors显示文摘 | Chang Y M Wu C Y Wu P W | 2013 | J Power Sources2013，223，： | 1 |
| 12 | Recent trends and some applications of isothermal titration calorimetry in biotechnology显示文摘 | Roselin L S Lin M S Lin P H Chang Y Chen W Y | | 0，，01： | 1 |
| 13 | Prognostic signifi- cance of ^18F- FDG PET parameters and plasma Epstein -Barr vi- rus DNA load in patients with nasopharyngeal carcinoma 显示文摘 | CHANG K P TSANG N M LIAO C T | 2012 | J Nucl Med2012，53，1： | 1 |
| 14 | Magnesium complexes containing bis-amido-oxazolinate ligands as efficient catalysts for ring opening polymerisation of L-lactide显示文摘 | CHEN M T CHANG P J HUANG C A | 2009 | Dalton Transactions2009，41，： | 1 |
| 15 | Light emitting diodes reliability review显示文摘 | CHANG M H DAS D VARDE P V | 2012 | Mieroeleetronics Re- liability2012，52，5： | 1 |
| 16 | A I - D analysis of ejector performance 显示文摘 | Huang B J Chang J M Wang C P | 1995 | International Journal of Refrigeration1995，18，6： | 1 |
| 17 | Nucleotide sequences of goose circovirus isolated in Taiwan 显示文摘 | Chen C L Chang P C Lee M S | 2003 | Avian Pathol2003，32，： | 1 |
| 18 | Involvement of PI3K/ Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation : a target for cancer chemotherapy 显示文摘 | Chang F Lee J T Navolanic P M | 2003 | Leukemia2003，17，3： | 1 |
| 19 | Investigation of crystallinity effects on the surface of oxygen plasma treated low density polyethylene using X-ray photoelectron spectroscopy显示文摘 | Kwang S K Chang M R Chan S P | 2003 | Polymer2003，，44： | 1 |
| 20 | An experi- mental study on biomass air-steam gasification in a flu- idized bed 显示文摘 | LV P M XIONG Z H CHANG J | 2004 | Bioresource and Technology2004，95，1： | 1 |
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