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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 | Hepatocellular carcinoma: Review of disease and tumor biomarkers显示文摘Hepatocellular carcinoma(HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest. | Jin Un Kim Mohamed I F Shariff Mary M E Crossey Maria Gomez-Romero Elaine Holmes I Jane Cox Haddy K S Fye Ramou Njie Simon D Taylor-Robinson | 2016 | World Journal of Hepatology2016，8，10： | 13 |
| 3 | Risk-adjustment in hepatobiliarypancreatic surgery显示文摘AIM: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA),APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery.We describe especially the limitations and advantages of risk in stratifying the patients.METHODS: We investigated 177 randomly chosen patients undergoing eledive complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors.Primary endpoint was in-hospital mortality and morbidity.Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality.RESULTS: The operative mortality in the series was 3.95% .This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Postoperative complications amounted to 45% with 24 (13.6%)patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18,P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117)or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR),pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery.CONCLUSION: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities. | Hemant M Kocher Paris P Tekkis Palepu Gopal Ameet G Patel Simon Cottam Irving S Benjamin | 2005 | World Journal of Gastroenterology2005，11，16： | 3 |
| 4 | 光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。 | Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 | 2013 | 国际病理科学与临床杂志2013，33，3： | 3 |
| 5 | Synthesis of CMP-NeuAc from N-acetylglucosamine: Generation of CTP from CMP using adenylate kinase 显示文摘 | Simon E S Bednarski M D Whitesides G M | 1988 | J Am Chem Soc1988，110，： | 2 |
| 6 | Strategies to tackle the challenges of external beam radiotherapy for liver tumors显示文摘Primary and metastatic liver cancer is an increasingly common and difficult to control disease entity.Radiation offers a non-invasive treatment alternative for these patients who often have few options and a poor prognosis.However,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose regimen.This article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy guidelines.Specific patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with radiation.Indeed,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special consideration.Implementing a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint selection.Strategies to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or tracking.Localization of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin management.Finally,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies. | Michael I Lock Jonathan Klein Hans T Chung Joseph M Herman Edward Y Kim William Small Nina A Mayr Simon S Lo | 2017 | World Journal of Hepatology2017，9，14： | 2 |
| 7 | Longterm multiple color imaging of live cells using quantum dot bioconjugates 显示文摘 | Jaiswal J K Mattoussi H Mauro J M Simon S F | 2003 | Nature Biotechnolgy2003，21，： | 1 |
| 8 | The relationship among biases, mispereeptions, and the introduction of pioneering products: Examining differences in venture decision Contexts 显示文摘 | Simon M Houghton S M | 2002 | Entrepreneurship Theory and Practice2002，，： | 1 |
| 9 | Generalized selection combining based on the log-likelihood ratio显示文摘 | Kim S W Kim Y G and Simon M K | 2004 | IEEE Transactions on Communications2004，52，4： | 1 |
| 10 | Porous Cobalt(II)-organic frameworks with corrugated walls:structurally robust gas-sorption materials显示文摘 | Simon M H Chang J S Sung H J | 2007 | An-gew Chem Int Ed2007，46，12： | 1 |
| 11 | Stability of clay minerals in acid显示文摘 | Simon D E Anderson M S | 1942 | SPE1942，2，： | 1 |
| 12 | Preparation of phosphoenol-pyruvate from D-O-3-phosphoglyceric acid for use in regeneration of ATP显示文摘 | SIMON E S GRABOWSKI S WHITESIDES G M | 1989 | Journal of the American Chemical Society1989，111，24： | 1 |
| 13 | Long-term multiple color imaging of live cells using quantum dot bioconjugates显示文摘 | JAISWAL J K MATTOUSSI H D SIMON S M | 2003 | Nature Biotechnol2003，21，1： | 1 |
| 14 | Laundry waste-water treatment using coagulation and membrane filtration 显示文摘 | Sostar-Turka S Petfinic I Simonic M | 2005 | Resources Conservation and Recycling2005，44，2： | 1 |
| 15 | Wastewater treatment after reactiveprinting显示文摘 | Sostar T S Simonic M Petrinic I | 2005 | Dyes and Pigments2005，64，2： | 1 |
| 16 | Expression of bone morphogenetic protein-7 mRNA in normal and is chemic adult rat kidney 显示文摘 | Simon M Maresh J G Harris S E | 1999 | Am J Physiol1999，276，： | 1 |
| 17 | Direct reprogramming of human astrocytes into neural stem cells and neurons 显示文摘 | Corti S Nizzardo M Simone C | 2012 | Exp Cell Res2012，318，13： | 1 |
| 18 | A review of ac- celerated carbonation technology in the treatment of cement- based materials and sequestration 'of CO2 显示文摘 | Fernandez Bertos M Simons S J R Hills C D | 2004 | Journal of Hazard- ous Materia/s2004，112，3： | 1 |
| 19 | High-dose vasopressin is not superior to norepinephrine in septic shock显示文摘 | Klinzing S Simon M Reinhart K | 2003 | Crit Care Med2003，31，： | 1 |
| 20 | On neighbor-selection strategy in hybrid peer-to-peer networks显示文摘 | Simon G M Koo Karthik Kannan C S George Lee | 2006 | Future Generation Computer Systems2006，22，： | 1 |
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