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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 | Hepatitis B virus infection显示文摘 | Christian Trépo Henry L Y Chan Anna Lok | 2014 | 2014 (9959)2014，，9959： | 6 |
| 3 | Economic impact of minimally invasive lumbar surgery显示文摘Cost effectiveness has been demonstrated for traditional lumbar discectomy, lumbar laminectomy as well as for instrumented and noninstrumented arthrodesis. While emerging evidence suggests that minimally invasive spine surgery reduces morbidity, duration of hospitalization, and accelerates return to activites of daily living, data regarding cost effectiveness of these novel techniques is limited. The current study analyzes all available data on minimally invasive techniques for lumbar discectomy, decompression, short-segment fusion and deformity surgery. In general, minimallyinvasive spine procedures appear to hold promise in quicker patient recovery times and earlier return to work. Thus, minimally invasive lumbar spine surgery appears to have the potential to be a cost-effective intervention. Moreover, novel less invasive procedures are less destabilizing and may therefore be utilized in certain indications that traditionally required arthrodesis procedures. However, there is a lack of studies analyzing the economic impact of minimally invasive spine surgery. Future studies are necessary to confirm the durability and further define indications for minimally invasive lumbar spine procedures. | Christoph P Hofstetter Anna S Hofer Michael Y Wang | 2015 | World Journal of Orthopedics2015，6，2： | 4 |
| 4 | Hepatitis B virus infection显示文摘 | Christian Trépo Henry L Y Chan Anna Lok | 2014 | The Lancet . 2014 (9959)2014，，： | 3 |
| 5 | TNF activates calcium-nuclear fac- tor of activated T cells (NFAT)cl signaling pathways in hu- man macrophages显示文摘 | Anna Y Xu K Chen J | 2011 | PNAS2011，108，： | 1 |
| 6 | Hematopoietic stem cells convert into liver cells within days without fusion 显示文摘 | JANG Y Y STEPHEN B B ANNA M D | 2004 | Nature Cell Biolo2004，6，6： | 1 |
| 7 | Numerical investigation on the dynamic behavior of advanced ceramics显示文摘 | Rena C Y Gonzalo R Anna P | 2004 | Engineering Fracture Mechanics2004，71，： | 1 |
| 8 | Prolactin-releasing peptide,a possible modulator of prolactin in the euryhaline silver sea bream(Sparus sarba) : A molecular study 显示文摘 | ANNA K Y K NORMAN Y S W | 2008 | General and Comparative Endocrinology2008，158，： | 1 |
| 9 | Phenolic and antioxidant composition of by-products from the cider industry:apple pomace显示文摘 | García Y D Belén S V Anna P L | 2009 | Food Chem2009，117，： | 1 |
| 10 | Pt-SnO2-Pd/C electrocatalyst with enhanced activity and durability for the oxygen reduction reaction at low Pt loading: The effect of carbon support type and activation显示文摘 | Anna I Carolyn T Ye S Y | 2010 | J Phys Chem2010，114，16： | 1 |
| 11 | Plasma isoflavone levels versus self-reported soy isoflavone levels in Asian- American women in Los Angeles County 显示文摘 | Anna H W Mimi C Y Chui C T | 2004 | Carcinogenesis2004，25，1： | 1 |
| 12 | Formation of oxynitride as the photocatalytic enhancing site in nitrogen-doped titanium nanocatalyst:comparison to commerical nanopowder显示文摘 | CHEN X B LOU Y B ANNA C S | 2005 | Adv Funct Mater2005，15，1： | 1 |
| 13 | A new light trapping TCO for nc-Si:H solar cells显示文摘 | Anna Selvan J A Delahoy Alan E Guo S Y | | 0，，： | 1 |
| 14 | The Registry of the International Society for Heart and Lung Transplantation: Twenty-seventh official adult lung and heart-lung transplant report-2010 显示文摘 | Christie J D Leah B Anna Y | 2010 | J Heart Lung Transplant2010，29，10： | 1 |
| 15 | Use of reactive sur- {ants in basalt fiber reinforced polypropylene composites显示文摘 | Matko S Z Anna P Marosi G Y | 2003 | Macromol Symp2003，202，： | 1 |
| 16 | Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity显示文摘 | Shvedova Anna A Fabisiak James P Kisin Elena R Murray Ashley R Roberts Jenny R Tyurina Yulia Y Antonini James M Feng Wei Hong Kommineni Choudari Reynolds Jeffrey Barchowsky Aaron Castranova Vince Kagan Valerian E | 2008 | American Journal of Respiratory Cell and Molecular Biology2008，，5： | 1 |
| 17 | Phenolic and antioxidant compo- sition of by-products from the cider industryt Apple pomace 显示文摘 | Garcia Y D Bel6n S V Anna P L | 2009 | Food Chem2009，117，： | 1 |
| 18 | Delayed neuronal death following perinatal asphyxia in rat显示文摘 | Dell Anna E Chen Y Engidawork E | 1997 | Exp Brain Res1997，115，： | 1 |
| 19 | Forrmtion ofoxynitride as the photocatalytic enhancing site in nitrogendoped titaniam nanocatalyst: comparison to commercial nanopowder显示文摘 | CHEN X B LOU Y B ANNA C S | 2005 | Adv Funct Mater2005，15，1： | 1 |
| 20 | Formation of Oxynitride as the Photocatalytic Enhancing Site in Nitro- gen-doped Titania Nanocatalysts: Comparison to a Commer- cial Nanopowder 显示文摘 | CHEN X B LOU Y B SAMIA ANNA C S | 2005 | Advanced Functional Materials2005，15，1： | 1 |
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