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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 | Angiogenic markers endoglin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine tumors显示文摘AIM:To investigate the expression and potential prognostic role of vascular endothelial growth factor(VEGF) and endoglin in gastroenteropancreatic neuroendocrine tumors(GEP-NETs) . METHODS:Microvessel density(MVD) in GEP-NETs was evaluated using endoglin and CD31 immunohistochemistry.In addition,tissue levels of endoglin and VEGF were determined in homogenates by ELISA. RESULTS:Endoglin was highly expressed on tumor endothelial cells.CD31 MVD in GEP-NETs was significantly higher compared to endoglin MVD(P<0.01) .Two-tofour-fold higher tissue levels of endoglin and VEGF were seen in tumors compared to associated normal tissue. This increased endoglin tissue expression in tumors was significantly related to tumor size(P<0.01) ,presence of metastases(P=0.04) ,and a more advanced tumor stage(P=0.02) ,whereas expression of VEGF was not. CONCLUSION:We suggest that endoglin is a potential marker to indicate and predict metastases,which might be useful in the post-resection therapeutic approach of patients with GEP-NETs. | Patricia Kuiper Lukas JAC Hawinkels Eveline SM de Jonge-Muller Izk Biemond Cornelis BHW Lamers Hein W Verspaget | 2011 | World Journal of Gastroenterology2011，17，2： | 4 |
| 3 | Prostate cancer upgrading or downgrading of biopsy Gleason scores at radical prostatectomy:prediction of'regression to the mean'using routine clinical features with correlating biochemical relapse rates显示文摘Recommendations for managing clinically localized prostate cancer are structured around clinical risk criteria,with prostate biopsy(PB)Gleason score(GS)being the most important factor.Biopsy to radical prostatectomy(RP)specimen upgrading/downgrading is welldescribed,and is often the ratio nale for costly imaging or genomic studies.We prese nt simple,no-cost an a lyses of clinical parametersto predict which GS 6 and GS 8 patients will change to GS 7 at prostatectomy.From May 2006 to December 2012,1590 patientsunderwent robot-assisted radical prostatectomy(RARP).After exclusions,we identified a GS 6 cohort of 374 patients and a GS 8cohort of 91 patients.During this era,>1000 additional patients were enrolled in an active surveillanee(AS)program.For GS 6,265(70.9%)of 374 patients were upgraded,and the cohort included 183(48.9%)patients eligible for AS by the Prostate Cancer ResearchInternational Active Surveillance Study(PRIAS)standards,of which 57.9%were upgraded.PB features that predicted a>90%chanceof upgrading included≥7 cores positive,maximum foci length≥8 mm in any core,and total tumor involvement≥30%.For GS 8,downgrading occurred in 46(50.5%),which was significantly higher for single core versus multiple cores(80.4%vs 19.6%,P=0.011).Biochemical recurre nee(BCR)occurred in 3.4%of GS 6 upgraded versus 0%non upgraded,and in GS 8,19.6%downgraded versus42.2%nondown graded.In coun seling men with clin ically localized prostate can cer,the odds of GS cha nge should be presented,andcertain men with high-volume GS 6 or low-volume GS 8 can be counseled with GS 7-based recommendations. | Muammer Altok Patricia Troncoso Mary F Achim Surena F Matin Graciela N Gonzalez John W Davis | 2019 | Asian Journal of Andrology2019，21，6： | 4 |
| 4 | Comparison of Topical Cyclosporine, Punctal Occlusion, and a Combination for the Treatment of Dry Eye显示文摘 | Calvin W Roberts Patricia E Carniglia Brian G Brazzo | 2007 | Cornea2007，，7： | 2 |
| 5 | Long-term research and development needs for wind energy for the time frame 2000-2020显示文摘 | SVEN ERIK T PATRICIA W | 2002 | Wind Energy2002，5，1： | 1 |
| 6 | Seller-buyer Interaction during the commercialization of technological innovation显示文摘 | Athaide Gerard A Patricia W | 1996 | Journal of Product Innovation Management1996，13，5： | 1 |
| 7 | Asthma in Australia 2005 显示文摘 | Guy BM Patricia KC Margaret W | 2005 | Med J Australia2005，183，： | 1 |
| 8 | MAS NMR,TPR and TEM studies of the interaction of NiMo with alumina and silicaalumina supports显示文摘 | Qu L L Zhang W P Patricia J | | 0，，： | 1 |
| 9 | National natural capital accounting with the ecological footprint concept显示文摘 | Mathis W Larry O Patricia B | 1999 | Ecological Economics1999，29，： | 1 |
| 10 | Cultural competence in mental health care: A review of model evaluations显示文摘 | Kamaldeep B Nasir W Patricia E | 2007 | BMC Health Service Research2007，7，： | 1 |
| 11 | Kinetic family drawing scoring method forcross-cultural studies 显示文摘 | Patricia W Vija BL | 2000 | Arts Psychother2000，27，3： | 1 |
| 12 | Emergency preparedness and bioterrorism: a sur- vey of the Nebraska medical center staff and physicians 显示文摘 | Patricia A Lenaghan Philip W Smith Deepali Ganga-har | 2006 | Journal of Emergency Nursing2006，，5： | 1 |
| 13 | A review and update of the current status of the vasculaturedisabling agent combretastatin-A4 phosphate(CA4P)显示文摘 | SIEMA D W Chaplin D J Patricia A W | 2009 | Expert Opin Investig Drugs2009，18，2： | 1 |
| 14 | Supporting diabetes self - manage- ment in primary care: Pilot - study of a group - based programme focu- sing on diet and exercise 显示文摘 | Hilde B Patricia S Johan W | 2009 | Primary Care Diabe2009，3，2： | 1 |
| 15 | Diabetes antibody standardization program:first assay proficiency evaluation显示文摘 | Bingley J Bonfifacio E Patricia W | 2003 | Diabetes2003，52，： | 1 |
| 16 | A novel,rapid assay for detection and differentiation of serotype-c antibodies to Venezuelane quine encephalitis complex alphaviruses显示文摘 | Eryu W Slobodan P Patricia V | | 0，，06： | 1 |
| 17 | Diabetes anti- body standardization program:first assay proficiency eval- uation显示文摘 | Bingley J Bonififacio E Patricia W | 2003 | Diabetes2003，52，7： | 1 |
| 18 | Automa- ted meteorological reports from commercial aircraft 显示文摘 | Moninge W R Richard D M Patricia M P | 2003 | Bulletin of The American Meteorological Socie ty2003，84，2： | 1 |
| 19 | Platinum metal - based intermetallics for high - temperature service 显示文摘 | Ira M W Patricia J H | 2000 | Platinum Metals Rev2000，44，4： | 1 |
| 20 | National natural capital accounting with the ecological footprint concept 显示文摘 | Mathis W Larry O Patricia B | 1999 | Ecological Economics1999，29，： | 1 |
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