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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 | Evaluating the accuracy of American Society for Gastrointestinal Endoscopy guidelines in patients with acute gallstone pancreatitis with choledocholithiasis显示文摘BACKGROUND Acute gallstone pancreatitis(AGP) is the most common cause of acute pancreatitis(AP) in the United States. Patients with AGP may also present with choledocholithiasis. In 2010, the American Society for Gastrointestinal Endoscopy(ASGE) suggested a management algorithm based on probability for choledocholithiasis, recommending additional imaging for patients at intermediate risk and endoscopic retrograde cholangiopancreatography(ERCP) for patients at high risk of choledocholithiasis. In 2019, the ASGE guidelines were updated using more specific criteria to categorize individuals at high risk for choledocholithiasis. Neither ASGE guideline has been studied in AGP to determine the probability of having choledocholithiasis.AIM To determine compliance with ASGE guidelines, assess outcomes, and compare 2019 vs 2010 ASGE criteria for suspected choledocholithiasis in AGP.METHODS We conducted a retrospective cohort study of 882 patients admitted with AP to a single tertiary care center from 2008-2018. AP was diagnosed using revised Atlanta criteria and AGP was defined as the presence of gallstones on imaging or with cholestatic pattern of liver injury in the absence of another cause. Patients with chronic pancreatitis and pancreatic malignancy were excluded as were those who went directly to cholecystectomy prior to assessment for choledocholithiasis. Patients were assigned low, intermediate or high risk based on ASGE guidelines. Our primary outcomes of interest were the proportion of patients in the intermediate risk group undergoing magnetic resonance cholangiopancreatography(MRCP) first and the proportion of patients in the high risk group undergoing ERCP directly without preceding imaging. Secondary outcomes of interest included outcome differences based on if guidelines were not adhered to. We then evaluated the diagnostic accuracy of 2019 in comparison to the 2010 ASGE criteria for patients with suspected choledocholithiasis. We performed the t test or Wilcoxon rank sum test, as appropriate, to analyze if there were outcome differences based on if guidelines were not adhered to. Kappa coefficients were calculated to measure the degree of agreement between pairs of variables.RESULTS In this cohort, we identified 235 patients with AGP of which 79 patients were excluded as they went directly to surgery for cholecystectomy without prior MRCP or ERCP. Of the remaining 156 patients, 79 patients were categorized as intermediate risk and 77 patients were high risk for choledocholithiasis according to the 2010 ASGE guidelines. Among 79 intermediate risk patients, 54(68%) underwent MRCP first whereas 25 patients(32%) went directly to ERCP. For the 54 patients with intermediate risk who had MRCP first, 36 patients had no choledocholithiasis while 18 patients had evidence of choledocholithiasis prompting ERCP. Of these patients, ERCP confirmed stone disease in 11 patients. Of the 25 intermediate risk patients who directly underwent ERCP, 18 patients had stone disease. One patient with a normal ERCP developed post ERCP pancreatitis. Patients undergoing MRCP in this group had a significantly longer length of stay(5.0 vs 4.0 d, P = 0.02). In the high risk group, 64 patients(83%) had ERCP without preceding imaging, of which, 53 patients had findings consistent with choledocholithiasis, of which 13 patients(17%) underwent MRCP before ERCP, all of which showed evidence of stone disease. Furthermore, all of these patients ultimately had an ERCP, of which 8 patients had evidence of stones and 5 had normal examination.RESULTS Our cohort also demonstrated that 58% of all 156 patients with AGP had confirmed choledocholithiasis(79% of the high risk group and 37% of the intermediate group when risk was assigned based on the 2010 ASGE guidelines). When the updated 2019 ASGE guidelines were applied instead of the original 2010 guidelines, there was moderate agreement between the 2010 and 2019 guidelines(kappa = 0.46, 95%CI: 0.34-0.58). Forty-two of 77 patients were still deemed to be high risk and 35 patients were downgraded to intermediate risk. Thirty-five patients who were originally assigned high risk were reclassified as intermediate risk. For these 35 patients, 26 patients had ERCP findings consistent with choledocholithiasis and 9 patients had a normal examination. Based on the 2019 criteria, 9/35 patients who were downgraded to intermediate risk had an unnecessary ERCP with normal findings(without a preceding MRCP).CONCLUSION Two-thirds in intermediate risk and 83% in high risk group followed ASGE guidelines for choledocholithiasis. One intermediate-group patient with normal ERCP had post-ERCP AP, highlighting the risk of unnecessary procedures. | Supisara Tintara Ishani Shah William Yakah Awais Ahmed Cristina S Sorrento Cinthana Kandasamy Steven D Freedman Darshan J Kothari Sunil G Sheth | 2022 | World Journal of Gastroenterology2022，28，16： | 3 |
| 3 | Host plant resistance to blackmargined aphids on pecan显示文摘 | Tommy E T Grauke L J Steven G S | 2000 | Journal American Pomological Society2000，54，4： | 1 |
| 4 | The influence of ultimate pH and intramuscular fat content on pork tenderness and tenderization 显示文摘 | van Laack R L Stevens S G Stalder K J | 2001 | Journal of Animal Science2001，79，2： | 1 |
| 5 | Residential magnetic fields and the risk of breast cancer显示文摘 | DAVIS S MIRICK D K STEVENS R G | 2002 | Am J Epidemiol2002，155，5： | 1 |
| 6 | Immune and pathologic responses in mice infected with Brucella abortus 19, RB51, or 2308 显示文摘 | Stevens M G Olsen S C Pugh G W | 1994 | Infec Immunity1994，62，： | 1 |
| 7 | High-performance liquid chromatographic analysis of metabolites of the nicotine-derived nitrosamines,N′-Nitrosonornicotine and4-(methylni-trosamino)-l-(3-pyridyl)-1-butanone显示文摘 | Steven G Carmell A Hecht S S | 1985 | Anal Biochem1985，145，： | 1 |
| 8 | Comparison of immune responses and resistance to Brucellosis in mice vaccinated with Brucella abortus 19 or RB51 显示文摘 | Stevens M G Olsen S C Pugh G W | 1995 | Infect Immun1995，63，： | 1 |
| 9 | Negative pressure wound therapy:a vacuum of evidence?显示文摘 | Steven G Marc M Stefan S | 2008 | Arch Surg2008，143，2： | 1 |
| 10 | Orbital maneuvering with electrodynam- ie tethers显示文摘 | Steven G T Hakan S | 2003 | Journal of Guidance Control and Dynamics2003，26，5： | 1 |
| 11 | Amulti-institutional review of radiosurgery alone vs,radiosurgery with whole brain radiotherapy as the initial management of brain metastases 显示文摘 | PENNY K S JOHN H S STEVEN J G | 2002 | Int J Radiation on Cology Biol Phys2002，53，： | 1 |
| 12 | A quantification of short-term macroaggregate dynamics: influences of wheat residue input and texture显示文摘 | STEVEN D G JOHAN S CYNTHIA B | 2005 | Soil Biology & Biochemistry2005，37，： | 1 |
| 13 | Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and inflammatory diseases 显示文摘 | Schett G Sloan V S Stevens R M | 2010 | Ther Adv Musculoskelet Dis2010，2，5： | 1 |
| 14 | Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans显示文摘 | Rhee Eugene P Cheng Susan Larson Martin G Walford Geoffrey A Lewis Gregory D McCabe Elizabeth Yang Elaine Farrell Laurie Fox Caroline S O’Donnell Christopher J Carr Steven A Vasan Ramachandran S Florez Jose C Clish Clary B Wang Thomas J Ger | 2011 | Journal of Clinical Investigation2011，，4： | 1 |
| 15 | Anticompetitive exclusion: raising Rivals: costs to achieve power over price显示文摘 | Thomas G K Steven C S | 1986 | Yale Law Journal1986，96，： | 1 |
| 16 | Shell-side mass-transfer performance in hollow- fiber membrane contactors 显示文摘 | SHEN S F KENTISH S E STEVENS G W | 2010 | Solvent Extraction and Ion Exchange2010，28，6： | 1 |
| 17 | Residential magneticfields and the risk of breast cancer显示文摘 | Davis S Mirick D K Stevens R G | 2002 | American Journalof Epidemiology2002，155，5： | 1 |
| 18 | The effect of condensable minor components on the gas separation performance of polymeric membranes for carbon dioxide capture显示文摘 | Scholes C A Kentish S E Stevens G W | 2009 | Energy Procedia2009，1，： | 1 |
| 19 | Re- centprogress in the U Maryland, Multiwave Cherenkov Generator Program 显示文摘 | Abedk Steven H G Gregory S N | 1991 | Bull Am Phys Soc1991，36，： | 1 |
| 20 | Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer显示文摘AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic adenocarcinoma.METHODS From April 2010 to September 2013,15 patients with initially unresectable pancreatic cancer were treated withproton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy(RBE) to the gross disease and 1 patient received 50.40 Gy(RBE) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration,of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included:Laparoscopic standard pancreaticoduodenectomy(n = 3),open pyloris-sparing pancreaticoduodenectomy(n = 1),and open distal pancreatectomy with irreversible electroporation(IRE) of a pancreatic head mass(n = 1). RESULTS The median patient age was 60 years(range,51-67). The median duration of surgery was 419 min(range,290-484),with a median estimated blood loss of 850 cm^3(range,300-2000),median ICU stay of 1 d(range,0-2),and median hospital stay of 10 d(range,5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection(n = 1),delayed gastric emptying(n = 1),and ischemic gastritis(n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient,after negative pancreatic head biopsies,underwent IRE followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo(range,10-30).CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after high-dose [59.4 Gy(RBE)] proton radiotherapy with a high rate of local control,acceptable surgical morbidity,and a median survival of 24 mo. | Kathryn E Hitchcock R Charles Nichols Christopher G Morris Debashish Bose Steven J Hughes John A Stauffer Scott A Celinski Elizabeth A Johnson Robert A Zaiden Nancy P Mendenhall Michael S Rutenberg | 2017 | World Journal of Gastrointestinal Surgery2017，9，4： | 1 |
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