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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 | Challenges in diagnosing mesenteric ischemia显示文摘Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia. | Teun C van den Heijkant Bart AC Aerts Joep A Teijink Wim A Buurman Misha DP Luyer | 2013 | World Journal of Gastroenterology2013，19，9： | 31 |
| 3 | Current status and perspectives of immune-based therapiesfor hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is a frequent cancer with a high mortality.For early stage cancer there are potentially curative treatments including local ablation,resection and liver transplantation.However,for more advanced stage disease,there is no optimal treatment available.Even in the case of a'curative'treatment,recurrence or development of a new cancer in the precancerous liver is common.Thus,there is an urgent need for novel and effective(adjuvant)therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC.The unique immune response in the liver favors tolerance,which remains a genuine challenge for conventional immunotherapy in patients with HCC.However,even in this'immunotolerant'organ,spontaneous immune responses against tumor antigens have been detected,although they are insufficient to achieve significant tumor death.Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens,which enhances spontaneous immune response.New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation.Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success.In this review,we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma,which could change disease progression in the near future. | Maridi Aerts DaphnéBenteyn Hans Van Vlierberghe Kris Thielemans Hendrik Reynaert | 2016 | World Journal of Gastroenterology2016，22，1： | 24 |
| 4 | Challenges in diagnosing adhesive small bowel obstruction显示文摘Adhesive small bowel obstruction(ASBO)is the most frequently encountered surgical disorder of the small intestine.Up to 80%of ASBO cases resolve spontaneously and do not require invasive treatment.It is important to identify such patients that will benefit from conservative treatment in order to prevent unnecessarily exposing them to the risks associated with surgical intervention,such as morbidity and further adhesion formation.For the remaining ASBO patients,timely surgical intervention is necessary to prevent small bowel strangulation,which may cause intestinal ischemia and bowel necrosis.While early identification of these patients is key to decreasing ASBO-related morbidity and mortality,the non-specific signs and laboratory findings upon clinic presentation limit timely diagnosis and implementation of appropriate clinical management.Combining the clinical presentation findings with those from other diagnostic imaging modalities,such as abdominal X-ray,computed tomography-scan and water-soluble contrast studies,will improve diagnosis of ASBO and help clinicians to better evaluate the potential of conservative management as a safe strategy for a particular patient.Nonetheless,patients who present with moderate findings by all these approaches continue to represent a challenge.A new diagnostic strategy is urgently needed to further improve our ability to identify early signs of strangulated bowel,and this diagnostic modality should be able to indicate when surgical management is required.A number of potential serum markers have been proposed for this purpose,including intestinal fatty acid binding protein andα-glutathione S transferase.On-going research is attempting to clearly define their diagnostic utility and to optimize their potential role in determining which patients should be managed surgically. | Thijs R van Oudheusden Bart AC Aerts Ignace HJT de Hingh Misha DP Luyer | 2013 | World Journal of Gastroenterology2013，19，43： | 7 |
| 5 | The Mineral Nutrition of Wild Plants Revisited: A Re-evaluation of Processes and Patterns显示文摘 | R. Aerts F.S. Chapin | 2000 | Advances in Ecological Research2000，，： | 5 |
| 6 | Controlled trial of metronidazole treatment for prevention of crohn’s recurrence after ileal resection显示文摘 | Paul Rutgeerts Martin Hiele Karel Geboes Marc Peeters Freddy Penninckx Raymond Aerts Raymond Kerremans | 1995 | Gastroenterology1995，，6： | 4 |
| 7 | Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy for pancreatic or periampullary tumours: a multicentre randomised trial显示文摘 | Baki Topal Steffen Fieuws Raymond Aerts Joseph Weerts Tom Feryn Geert Roeyen Claude Bertrand Catherine Hubert Marc Janssens Jean Closset | 2013 | Lancet Oncology2013，，7： | 2 |
| 8 | Current approaches in dendritic cell generation and future implications for cancer immunotherapy显示文摘 | TUYAERTS S AERTS J L CORTHALS J | 2007 | Cancer Immunol Immunother2007，56，10： | 1 |
| 9 | Laparoscopic common bile duct stone clearance with flexible choledochoscopy 显示文摘 | Topal B Aerts R Penninckx F | 2007 | Surg Endosc2007，21，12： | 1 |
| 10 | Intellectual capital dis- closure, cost of finance and finn value 显示文摘 | Orens R Aerts W Lybaert N | 2009 | Manage- ment Decision2009，47，20： | 1 |
| 11 | Determinants of complications and adequacy of surgical resection in laparoscopic versus open total gastrectomy for adenocarcinoma显示文摘 | B. Topal E. Leys N. Ectors R. Aerts F. Penninckx | 2008 | Surgical Endoscopy2008，，4： | 1 |
| 12 | Biomechanical analysis of the stance phase during barefoot and shod running显示文摘 | De Wit B De Clercq D Aerts P | | 0，，： | 1 |
| 13 | Biomechanical analysis of the stance phase during barefoot and shod running显示文摘 | De Wit B De Clercq D Aerts P | | 0，，： | 1 |
| 14 | Corporate Environmental Disclosure,Financial Markets and the Media:An International Perspective显示文摘 | Aerts W Cormier D Magnan M | 2008 | Ecological Economics2008，，64： | 1 |
| 15 | Somatic uniparental isodi- somy explains multifocality of glomuvenous malformations 显示文摘 | Amyere M Aerts M Brouillard P | 2013 | Am J Hum Genet2013，92，2： | 1 |
| 16 | Laparoscopic common bile duct stone clearance with flexible choledochoscopy 显示文摘 | Topal B Aerts R Penninckx F | 2007 | Surg Endosc2007，21，12： | 1 |
| 17 | Moraxella(Branhamella) catarrhalis BRO β -lactamase:a lipoprotein of gram-positive origin? 显示文摘 | Bootsma HJ Aerts PC Posthuma G | 1999 | J Bacteriol1999，8，： | 1 |
| 18 | Reactive eompatibilization of blends of poly(2,6-demethyl-1, 4-phenylene ether) and poly(butylene terephthalate) 显示文摘 | VAN AERT H A M VAN STEENPAAL GJ M NELISSEN L | 2001 | Polymer2001，42，： | 1 |
| 19 | The freezer defrosting: Global warming and litter decomposition rates in cold hiomes显示文摘 | Aerts R | 2006 | Journal of Ecology2006，94，： | 1 |
| 20 | A flexible, agent-based ICT architecture for virtual enterprise显示文摘 | Aerts A Szirbik N | 2002 | Computers in Industry2002，49，3： | 1 |
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