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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 | Mycophenolate mofetil for drug-induced vanishing bile duct syndrome显示文摘Amoxicillin/clavulanate is associated with liver injury, mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment, but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil. | S Simona Jakab A Brian West Dennis M Meighan Robert S Brown Jr William B Hale | 2007 | World Journal of Gastroenterology2007,13,45: | 8 |
| 3 | Model combining pre-transplant tumor biomarkers and tumor size shows more utility in predicting hepatocellular carcinoma recurrence and survival than the BALAD models显示文摘AIM To assess the performance of BALAD, BALAD-2 and their component biomarkers in predicting outcome of hepatocellular carcinoma(HCC) patients after liver transplant.METHODS BALAD score and BALAD-2 class are derived from bilirubin, albumin, alpha-fetoprotein(AFP), Lens culinaris agglutinin-reactive AFP(AFP-L3), and des-gammacarboxyprothrombin(DCP). Pre-transplant AFP, AFP-L3 and DCP were measured in 113 patients transplanted for HCC from 2000 to 2008. Hazard ratios(HR) for recurrence and death were calculated. Univariate and multivariate regression analyses were conducted. C-statistics were used to compare biomarker-based to predictive models. RESULTS During a median follow-up of 12.2 years, 38 patients recurred and 87 died. The HRs for recurrence in patients with elevated AFP, AFP-L3, and DCP defined by BALAD cut-off values were 2.42(1.18-5.00), 1.86(0.98-3.52), and 2.83(1.42-5.61), respectively. For BALAD, the HRs for recurrence and death per unit increased score were 1.48(1.15-1.91) and 1.59(1.28-1.97). For BALAD-2, the HRs for recurrence and death per unit increased class were 1.45(1.06-1.98) and 1.38(1.09-1.76). For recurrence prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs. 0.64, 0.61, 0.53, and 0.53 for BALAD, BALAD-2, Milan, and UCSF, respectively. Similarly, for death prediction, the combination of three biomarkers had the highest c-statistic of 0.66 vs 0.65,0.61, 0.52, and 0.50 for BALAD, BALAD-2, Milan, and UCSF. A new model combining biomarkers with tumor size at the time of transplant(S-LAD) demonstrated the highest predictive capability with c-statistics of 0.71 and 0.69 for recurrence and death. CONCLUSION BALAD and BALAD-2 are valid in transplant HCC patients, but less predictive than the three biomarkers in combination or the three biomarkers in combination with maximal tumor diameter(S-LAD). | Nicha Wongjarupong Gabriela M Negron-Ocasio Roongruedee Chaiteerakij Benyam D Addissie Essa A Mohamed Kristin C Mara William S Harmsen J Paul Theobald Brian E Peters Joseph G Balsanek Melissa M Ward Nasra H Giama Sudhakar K Venkatesh Denise M Harnois Michael R Charlton Hiroyuki Yamada Alicia Algeciras-Schimnich Melissa R Snyder Terry M Therneau Lewis R Roberts | 2018 | World Journal of Gastroenterology2018,24,12: | 5 |
| 4 | Positron emission tomography scanning in the evaluation of hepatocellular carcinoma显示文摘 | M.Akram Khan Connie S Combs Elizabeth M Brunt Val J Lowe Michael K Wolverson Harvey Solomon Brian T Collins Adrian M.Di Bisceglie | 2000 | Journal of Hepatology2000,,5: | 2 |
| 5 | Advances in cellulose ester performance and application显示文摘 | Kevin J Edgar Charles M Buchanan John S Debenham Paul A Rundquist Brian D Seiler Michael C Shelton Debra Tindall | 2001 | Progress in Polymer Science2001,,9: | 2 |
| 6 | Urban Modification of Thunderstorms: An Observational Storm Climatology and Model Case Study for the Indianapolis Urban Region*显示文摘 | Niyogi Dev Pyle Patrick Lei Ming Arya S Pal Kishtawal Chandra M Shepherd Marshall Chen Fei Wolfe Brian | 2011 | Journal of Applied Meteorology and Climatology2011,,5: | 2 |
| 7 | Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett’s oesophagus: a prospective study显示文摘 | Thomas L Vaughan Linda M Dong Patricia L Blount Kamran Ayub Robert D Odze Carissa A Sanchez Peter S Rabinovitch Brian J Reid | 2005 | Lancet Oncology2005,,12: | 2 |
| 8 | Hemoglobin Concentrations Influence Birth Outcomes in Pregnant Afican- American Adolesents显示文摘 | Chang S C O'Brian K O Nathanson M S | | 0,,07: | 1 |
| 9 | Antifouling enzymes and the biochemistry of marine settlement显示文摘 | Jakob B K Rikke L M Brian S L | 2008 | Biotechn Adv2008,26,: | 1 |
| 10 | A Systematic Review and Meta analysis Evaluating Completeness and Outcomes o{ Robotic Tbyroidectomy 显示文摘 | Brian Hung Hin Lang M S Carloa K H | 2014 | The Laryngoscope2014,125,2: | 1 |
| 11 | Sohd-phase sediment toxicity identification evaluation in an agricultural stream显示文摘 | Bryn M Philips Brian S Anderson John W Hunt | 2006 | Environmental Toxicology and Chemistry2006,25,6: | 1 |
| 12 | 显示文摘 | Trewyn Brian G Whitman Chad M Lin Victor S Y | 2004 | Nanoletters2004,11,4: | 1 |
| 13 | Low-temperature polyol synthesis of AuCuSn2 and AuCuSn2:using solution chemistry to access ternary intermetallic compounds as nanocrystals显示文摘 | Brian M L Nattamai S P B Raymond E S | 2005 | JACS2005,,: | 1 |
| 14 | Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid显示文摘 | Brian M R Jennifer S Lee E S | 2007 | Lipids in Health and Disease2007,,6: | 1 |
| 15 | A survey of dynamic spectrum access 显示文摘 | ZHAO Qing BRIAN M S | 2007 | IEEE Signal Processing Magazine2007,24,3: | 1 |
| 16 | The hmuQ and hmuD genes from BradyrhizobiumJaponicum encode heme- degrading enzymes显示文摘 | Puri S 0' Brian M R | 2006 | J Bacteriol2006,188,18: | 1 |
| 17 | Detection in correlated impulsive noise using fourth20rder cumulant显示文摘 | | 1997 | IEEE Trans Signal Processing1997,50,3: | 1 |
| 18 | Dealing with globalisation at the regional and local level:The case of contemporary containerization显示文摘 | Robert J M Brian S Claude C | 2004 | The Canadian Geographer2004,48,4: | 1 |
| 19 | Thermoelectric materials:New approaches to an old problem显示文摘 | Gerald M Brian S Jeff S | 1997 | Phys Today1997,50,2: | 1 |
| 20 | Regulated gene insertion by steroid induced φC31 integrase 显示文摘 | Nynne S Brian M Trine D | 2008 | Nucl Acids Res2008,36,11: | 1 |