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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 | Sarcoplasmic reticulum Ca2+ATPase as a therapeutictarget for heart failure显示文摘 | Larissa Lipskaia Elie R Chemaly Lahouaria Hadri etal | 2010 | Expert Opin Biol Ther2010，10，1： | 1 |
| 3 | A nano-organized ethyl-ene oligomerization catalyst:Characterization and reactivity of the Ni(MeCN)6(BF4)2/-MCM-41/AIEt3 system显示文摘 | Michele O Souza de Larissa R | 2006 | Mi-croporous and Mesoporous Materials2006，，96： | 1 |
| 4 | Reverse knowledge trans- fer in MNES: subsidiary innovativeness and entry modes显示文摘 | RAM M LUCIA P LARISSA R | 2014 | Long Range Planning2014，47，1： | 1 |
| 5 | A nano-organized ethylene oligomerization catalyst: characterization and reactivity of the Ni (MeCN)6 ( BF4 ) 2/ -MCM-41/AlEt3 system 显示文摘 | Michele 0 De Souza Larissa R Rodrigues Heloise O Pastore | 2006 | Microporous and Mesoporous Materials2006，96，123： | 1 |
| 6 | New composite sorbent CaCl2 in mesopores for sorption cooling/heating显示文摘 | Mikhail T Larissa G Vyacheslav R | 2002 | International Journal of Thermal Science2002，41，5： | 1 |
| 7 | Video modeling and word identification in adolescents with Autism Spectrum Disorder 显示文摘 | LARISSA M JENNIFER L R SYCARAH F | 2015 | Child Lang Teach Ther2015，31，1： | 1 |
| 8 | Sarcoplasmic reticulum Ca^2+ ATPase as a therapeutic target for heart failure 显示文摘 | Larissa Lipskaia Elie R C Lahouaria H et at | 2010 | Expert Opin Biol Ther2010，10，1： | 1 |
| 9 | Associations of FASN gene polymorphisms with economical traits in Nellore cattle 显示文摘 | Fabio R P S Milena G C Larissa F S F | 2012 | Molecular Biology Reports2012，39，10： | 1 |
| 10 | Parent company benefits from reverse knowledge transfer:the role ofthe liability of new- ness in MNEs显示文摘 | LARISSA R GRAZIA D S | 2013 | Journal of World Business2013，48，1： | 1 |
| 11 | Image quality in a low radiation exposure protocol for retrospectively ECG-gated coronary CT angiog- raphy 显示文摘 | Tobias P Larissa K Dieter R | 2009 | A JR Am J Roentgenol2009，192，4： | 1 |
| 12 | Image quality in alow radiation exposure protocal for retrospectively ECG-gated coronary CT angiography 显示文摘 | Tobiss P Larissa R Dieter R | 2009 | AJR2009，192，4： | 1 |
| 13 | New composite sorbent CaCl2 in mesopores for sorption cooling/heating显示文摘 | Mikhail T Larissa G Vyacheslav R | 2002 | International Journal of Thermal Science2002，41，： | 1 |
| 14 | Acute Cholecystitis: MR Findings and Differentiation from Chronic Cholecystitis 显示文摘 | Ersan A R Jorge E Larissa B | 2007 | Radiology2007，244，1： | 1 |
| 15 | Dilute-acid hydrolysis of sugarcane bagasse at varying conditions 显示文摘 | LARISSA C VICTOR T O S GEORGE J M R | 2002 | Appl Biochem Biotechnol2002，，： | 1 |
| 16 | A nano-organized ethylene oligomerization catalyst: Characterization and reactivity of the Ni (MeCN) 6 ( BF, ) JA1-MCM-41/A1Et3 system 显示文摘 | Mich~le O de Souza Larissa R Rodrigues a Heloise O Pastore | 2006 | Micro- porous and Mesoporous Materials2006，96，13： | 1 |
| 17 | Sarcoplasmic reticulum Ca2+ATPase as a therapeutic target for heart failure显示文摘 | Larissa Lipskaia Elie R Chemaly Lahouaria Hadri | 2010 | Expert Opin Biol Ther2010，10，1： | 1 |
| 18 | Uncoupling protein 2 deficiency of non-cancerous tissues inhibits the progression of pancreatic cancer in mice显示文摘Background: Pancreatic ductal adenocarcinoma(PDAC) is a disease of the elderly mostly because its development from preneoplastic lesions depends on the accumulation of gene mutations and epigenetic alterations over time. How aging of non-cancerous tissues of the host affects tumor progression, however, remains largely unknown. Methods: We took advantage of a model of accelerated aging, uncoupling protein 2-deficient( Ucp2 knockout, Ucp2 KO) mice, to investigate the growth of orthotopically transplanted Ucp2 wild-type(WT) PDAC cells(cell lines Panc02 and 6606PDA) in vivo and to study strain-dependent differences of the PDAC microenvironment. Results: Measurements of tumor weights and quantification of proliferating cells indicated a significant growth advantage of Panc02 and 6606PDA cells in WT mice compared to Ucp2 KO mice. In tumors in the knockout strain, higher levels of interferon-γ m RNA despite similar numbers of tumor-infiltrating T cells were observed. 6606PDA cells triggered a stronger stromal reaction in Ucp2 KO mice than in WT animals. Accordingly, pancreatic stellate cells from Ucp2 KO mice proliferated at a higher rate than cells of the WT strain when they were incubated with conditioned media from PDAC cells. Conclusions: Ucp2 modulates PDAC microenvironment in a way that favors tumor progression and implicates an altered stromal response as one of the underlying mechanisms. | Denis Revskij Jakob Runst Camilla Umstätter Luise Ehlers Sarah Rohde Dietmar Zechner Manuela Bastian Brigitte Müller-Hilke Georg Fuellen Larissa Henze Hugo Murua Escobar Christian Junghanss Axel Kowald Uwe Walter Rüdiger Köhling Olaf Wolkenhauer Robert Jaster | 2023 | Hepatobiliary & Pancreatic Diseases International2023，22，2： | 0 |
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