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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 | 含矿流体混合反应与成矿作用的动力平衡模拟研究显示文摘本文在约定热液体系中成矿元素成矿速率(成矿过程中单位时间内单位体积所含成矿元素重量的变化)的基础上,借助于物质-热-化学-成矿四重全耦合的研究思路,构建了均匀热液体系、层状热液体系、岩浆侵入热液体系下成矿元素的迁移、富集、溶解与沉淀作用数值模型。模拟结果表明:(1)硫化物(H_2S)和硫酸盐(SO_(42-))流体的混合反应是成矿热液体系中铅、锌、铁成矿元素成矿的重要控制因素;(2)均匀介质、岩浆侵入或地质构造的存在,对成矿元素在成矿流体运移的速度、流线、温度分布和成矿元素的溶解与沉淀分布都有着各自的特征,不同的成矿环境或成矿背景制约了成矿元素的迁移与富集以及矿体的产出定位。暗示成矿环境及成矿速率对热液体系中成矿元素的沉淀与溶解具重要作用;成矿流体的混合反应是成矿作用发生的重要机制之一。在成矿理论研究中必须充分考虑不同地质构造因素的约束。 | 林舸 C B ZHAO 王岳军 B E HOBBS 龚纪文 | 2003 | 岩石学报2003,19,2: | 15 |
| 3 | Effective loading algorithm associated with explicit dynamic relaxation method for simulating static problems显示文摘Based on the fact that a static problem has an equivalent wave speed of infinity and a dynamic problem has a wave speed of finite value, an effective loading algorithm associated with the explicit dynamic relaxation method was presented to produce meaningful numerical solutions for static problems. The central part of the explicit dynamic relaxation method is to turn a time-independent static problem into an artificial time-dependent dynamic problem. The related numerical testing results demonstrate that: (1) the proposed effective loading algorithm is capable of enabling an applied load in a static problem to be propagated throughout the whole system within a given loading increment, so that the time-independent solution of the static problem can be obtained; (2) the proposed effective loading algorithm can be straightforwardly applied to the particle simulation method for solving a wide range of static problems. | 赵崇斌 彭省临 刘亮明 HOBBS B E ORD A | 2009 | Journal of Central South University2009,16,1: | 4 |
| 4 | Vorticity and noncoaxiality in progressive deformations显示文摘 | Means W D Hobbs B E Lister G S | 1980 | Journal of Structrual Geology1980,2,: | 1 |
| 5 | The relative effects of deformation and thermal advection on fluid pathways in basin-related mineralization显示文摘 | Mclellan J G Oliver N H S Hobbs B E | 2006 | Journal of Geochemical Exploration2006,89,: | 1 |
| 6 | Chronic subdural hematoma in the elderly:not a benign disease显示文摘 | Miranda LB Braxton E Hobbs J | 2011 | J Neurosurg2011,114,1: | 1 |
| 7 | Measuring the importance of transaction costs in cattle marketing 显示文摘 | Hobbs J E | 1997 | American Journal of Agricultural Economics1997,79,4: | 1 |
| 8 | Closer vertical co-ordination in agri-food supply chains: a conceptual framework and some preliminary evidence 显示文摘 | HOBBS J E YOUNG L M | 2000 | Supply Chain Management: An international Journal2000,5,3: | 1 |
| 9 | Struvite crystallisation and recovery using a stainless steel structure as a seed material显示文摘 | Le-Correa K S Valsami-Jones E Hobbs P | 2007 | Water Research2007,41,11: | 1 |
| 10 | A novel instrument for transient photoelasticity显示文摘 | Hobbs J W Greene R J and Patterson E A | 2003 | Experimental Mechanics2003,43,4: | 1 |
| 11 | Coccidia (Eiraeria spp) of wild rabbits in southwestern Australia显示文摘 | Hobbs R P Twigg L E | 1998 | Aust Vet J1998,76,: | 1 |
| 12 | Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detec- tion of sweet stimuli显示文摘 | Nie Y Vigues S Hobbs JR e al | 2005 | Curr Biol2005,15,21: | 1 |
| 13 | Radar imaging from geosynchronous orbit, temporal decorrelation aspects显示文摘 | Bruno D Hobbs S E | 2010 | IEEE Trans on Geoscience and Remote Sensing2010,48,7: | 1 |
| 14 | Impact of calcium on struvite crystal size, shape and purity 显示文摘 | Le Corre K Valsami -Jones E Hobbs P | 2005 | J of Cryst Growth2005,283,34: | 1 |
| 15 | Struvite crystallisation and recovery using a stainless steel structure as a seed material显示文摘 | Corre K S Jones E Hobbs P | 2007 | Water Research2007,41,11: | 1 |
| 16 | Vorticity and non-coaxialicy in progressive deformation显示文摘 | Hobbs B E Lister G S | 1980 | J Struct Geol1980,2,3: | 1 |
| 17 | Energy and nitrogen based estimates of Elk winter-range carrying capacity显示文摘 | Hobbs N T Baker D L Ellis J E | 1982 | J Wildl Manage1982,46,1: | 1 |
| 18 | Coccidia (Eimeria spp) of wild rabbits in southwestern Australia显示文摘 | Hobbs R P Twigg L E | 1998 | Aust Vet J1998,76,: | 1 |
| 19 | Impact of calcium on struvitc crystal size, shape and purity显示文摘 | Le Corre K S Valsami-Jones E Hobbs P | 2005 | Journal of Crystal Growth2005,283,34: | 1 |
| 20 | Recrystallization of single crystals of quartz显示文摘 | Hobbs B E | | 0,,: | 1 |