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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 | A high-quality genome assembly of quinoa provides insights into the molecular basis of salt bladder-based salinity tolerance and the exceptional nutritional value显示文摘 | Changsong Zou Aojun Chen Lihong Xiao Heike M Muller Peter Ache Georg Haberer Meiling Zhang Wei Jia Ping Deng Ru Huang Daniel Lang Feng Li Dongliang Zhan Xiangyun Wu Hui Zhang Jennifer Bohm Renyi Liu Sergey Shabala Rainer Hedrich Jian-Kang Zhu Heng Zhang | 2017 | Cell Research2017，27，11： | 22 |
| 3 | Parameters affecting different acoustic radiation force impulse applications in the diagnosis of fibrotic liver changes显示文摘AIM: To analyze the virtual touch tissue quantification(VTTQ) and virtual touch imaging quantification(VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements.METHODS: One hundred and eighty-six(104 women/82 men) of 323 subjects met the inclusion criteria(age > 18 years, no history of chronic or gastrointestinal disease, body-mass index(BMI) < 30 kg/m2, a fasting period of at least three hours, no history of hepatotoxic pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and normal findings upon ultrasound examination of the abdomen). Measurements were taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner acquired six measurements per position, thereby giving 24 measurements in total.RESULTS: The 95% confidence intervals of mean were1.23-1.29 m/s for VTTQ and 1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and 25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only superficial measurements in the right hepatic lobe with the VTIQ method exhibited an effect of age on shear wave velocity. Measurements acquired using the 6C1 probe with the VTTQ method showed no dependence on BMI. By comparison, BMI influenced measurements taken with the VTIQ method using the 9L4 probe in the superficial and deep areas of the right hepatic lobe, as well as in the left hepatic lobe(P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the right hepatic lobe(P = 0.0001, P = 0.0269). Significant differences were found between measurements with the 6C1(VTTQ) and 9L4 probes(VTIQ)(P = 0.0067), between superficial and deep measurements(P < 0.0001), and between the right and left lobes of the liver(P < 0.0001). CONCLUSION: Measurements in the right lobe and deep regions are preferable. Gender differences must be considered. BMI must be considered when assessing VTIQ technology. | Sabrina Galgenmueller Heike Jaeger Wolfgang Kratzer Stefan A Schmidt Suemeyra Oeztuerk Mark M Haenle Richard A Mason Tilmann Graeter | 2015 | World Journal of Gastroenterology2015，21，27： | 5 |
| 4 | Lack of microRNA‐101 causes E‐cadherin functional deregulation through EZH2 up‐regulation in intestinal gastric cancer显示文摘 | Joana Carvalho Nicole C van Grieken Patricia M Pereira Sónia Sousa Marianne Tijssen Tineke E Buffart Bego?a Diosdado Heike Grabsch Manuel AS Santos Gerrit Meijer Raquel Seruca Beatriz Carvalho Carla Oliveira | 2012 | J Pathol2012，，1： | 3 |
| 5 | HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value – conclusions from 924 cases of two independent series显示文摘 | Heike Grabsch Shivan Sivakumar Sally Gray Helmut E. Gabbert Wolfram Müller | 2010 | Cellular Oncology (-)2010，，1： | 3 |
| 6 | Trends in treatment and overall survival among patients with proximal esophageal cancer显示文摘BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures.Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT)have been implemented.The trends in(non-)surgical treatment and its impact on overall survival(OS)in patients with proximal esophageal cancer are unclear,related to its rare disease status.To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study,patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry.The proximal esophagus consists of the cervical esophagus and the upper thoracic section,extending to 24 cm from the incisors.Trends in radiotherapy,chemotherapy,and surgery,and OS were assessed.Analyses were stratified by presence of distant metastasis.Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS,adjusted for patient,tumor,and treatment characteristics.RESULTS In total,2783 patients were included.Over the study period,the use of radiotherapy,resection,and CRT in non-metastatic disease changed from 53%,23%,and 1%in 1989-1994 to 21%,9%,and 49%in 2010-2014,respectively.In metastatic disease,the use of chemotherapy and radiotherapy increased over time.Median OS of the total population increased from 7.3 mo[95%confidence interval(CI):6.4-8.1]in 1989-1994 to 9.5 mo(95%CI:8.1-10.8)in 2010-2014(logrank P<0.001).In non-metastatic disease,5-year OS rates improved from 5%(95%CI:3%-7%)in 1989-1994 to 13%(95%CI:9%-17%)in 2010-2014(logrank P<0.001).Multivariable regression analysis demonstrated a significant treatment effect over time on survival.In metastatic disease,median OS was 3.8 mo(95%CI:2.5-5.1)in 1989-1994,and 5.1 mo(95%CI:4.3-5.9)in 2010-2014(logrank P=0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer,likely to be associated with an increased use of CRT.Patterns in metastatic disease did not change significantly over time. | Judith de Vos-Geelen Sandra ME Geurts Liselot BJ Valkenburg-van Iersel Evelien JM de Jong Vivianne CG Tjan-Heijnen Margreet van Putten Valery EPP Lemmens Heike I Grabsch Nadia Haj Mohammad Frank JP Hoebers Chantal V Hoge Paul M Jeene Hanneke WM van Laarhoven Tom Rozema Marije Slingerland Grard AP Nieuwenhuijzen | 2019 | World Journal of Gastroenterology2019，25，47： | 2 |
| 7 | HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value – conclusions from 924 cases of two independent series显示文摘 | Heike Grabsch Shivan Sivakumar Sally Gray Helmut E. Gabbert Wolfram Müller | 2010 | Cellular Oncology . 2010 (1-2)2010，，1： | 2 |
| 8 | AFM lithography combined with optical hthography显示文摘 | Heike S Kajiyama H | 2000 | IEEE2000，1113，： | 1 |
| 9 | Sustainability, Clusters, and Competitiveness 显示文摘 | Sheila M Heike M | 2008 | Economic Development Quarterly2008，，22： | 1 |
| 10 | In vivo screening models of cisplatin-resistant human lung cancer cell lines using SCID mice 显示文摘 | HEIKE Y TAKAHASHI M OHIRA T | 1995 | Cancer Chemother Pha- macol1995，35，3： | 1 |
| 11 | Mixed model assembly alternatives for low-volume manufacturing:the case of the aerospace industry显示文摘 | HEIKE G RAMULU M SORENSON E | 2001 | International Journal of Production Economics2001，72，2： | 1 |
| 12 | 显示文摘 | TATIANA A S HEIKE M SERGIY A P | 2001 | J Chromatogr A2001，907，： | 1 |
| 13 | Upconverting luminescent nanoparticles for use in bioconjugation and bioimaging 显示文摘 | Heike S M Peter K Sayed M S | 2010 | Current Opinion in Chemical Biology2010，14，5： | 1 |
| 14 | Diabetes Risk Calculator: a simple tool for detecting undiagnosed diabetes and pre-diabetes 显示文摘 | HEIKES K E EDDY D M ARONDEKAR B | 2008 | Diabetes Care2008，31，5： | 1 |
| 15 | HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value – conclusions from 924 cases of two independent series显示文摘 | Heike Grabsch Shivan Sivakumar Sally Gray Helmut E. Gabbert Wolfram Müller | 2010 | Cellular Oncology (-)2010，，1： | 1 |
| 16 | HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value – conclusions from 924 cases of two independent series显示文摘 | Heike Grabsch Shivan Sivakumar Sally Gray Helmut E. Gabbert Wolfram Müller | 2010 | Cellular Oncology (-)2010，，1： | 1 |
| 17 | Chemo- therapy of colorectal cancer显示文摘 | Heike M Meyer zum Buschenfelde KH Knuth A | 1989 | Z Gastroenterol1989，27，9： | 1 |
| 18 | Isolation and characterization of bone marrow-derived mesenchymal progenitor cells with myogenic and neuronal properties显示文摘 | Shiota M Heike T Haruyama M | 2007 | Exp- CellRes2007，313，5： | 1 |
| 19 | Heat shock protein-peptide complexs for use in vaccines显示文摘 | Heike M Noll B Buschenfelde KHM | 1996 | J Leukoc Biol1996，60，2： | 1 |
| 20 | Type 2 diabetes mellitus and gender-specific risk for colorectal neoplasia显示文摘 | Heike Kr?mer Heiko Müller Christa Stegmaier Dietrich Rothenbacher Elke Raum Hermann Brenner | 2012 | European Journal of Epidemiology2012，，5： | 1 |
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