术后辅助肝动脉化疗栓塞对巨块型肝癌根治性切除术后生存的影响

目的:探讨巨块型肝癌根治性切除术后行辅助性经导管肝动脉化疗栓塞(transeatheter hepatic arterial chemo-embolization,TACE)治疗对术后生存的影响.方法:回顾性收集256例资料完整的巨块型肝癌患者,这些患者均接受了手术切除.其中136例患者于术后4～6周接受辅助性TACE治疗,另120例患者仅接受单纯手术切除.根据是否伴有残癌高危因素(子灶、门静脉二级分支以上的癌栓和包膜不完整)对所有患者进行分层分析,比较各组患者的术后生存率.结果:对于不伴有残癌高危因素的巨块型肝癌,术后辅助TACE组与单纯手术切除组的1、3、5年生存率分别为80.43%、59.92%、47.18%与74.05%、53.40%、45.77%,2组的生存率比较差异无统计学意义(P=0.769 3).对于伴有残癌高危因素的巨块型肝癌,术后辅助TACE组与单纯手术切除组的1、3、5年生存率分别为72.15%、32.27%、22.35%与45.36%、22.47%、19.67%,2组的生存率比较差异有统计学意义(P=0.004 9).COX回归分析表明,术后辅助TACE治疗[风险比(hazard ratio,HR)=0.620(95%的可信区间为0.441～0.870)]和残癌高危因素[HR=2.235(95%的可信区间为1.491～3.351)]是影响巨块型肝癌患者术后长期生存的独立危险因素.结论:巨块型肝癌患者术后行辅助性TACE治疗有助于提高术后的长期生存率,而其中伴有残癌高危因素的患者,其术后生存时间的延长更为明显.     

混合型小细胞肺癌外科治疗后预后分析

  目的  探索混合型小细胞肺癌（C-SCLC）术后患者生存的预后影响因素。  方法  回顾性分析2010年1月至2014年12月在上海交通大学附属胸科医院行肺癌根治性切除及系统性淋巴结清扫C-SCLC患者的临床资料。  结果  共计78例患者入组,其中C-SCLC合并大细胞神经内分泌肿瘤（large cell neuroendocrine carcinoma,LCNEC）患者所占比例最多（n=42）,其次是C-SCLC合并鳞癌（SCC）患者（n=18）、C-SCLC合并腺癌（AC）患者（n=10）及C-SCLC合并腺鳞癌（ASC）患者（n=8）。本研究队列5年生存率（OS）39.1%。多因素Cox回归分析表明:肿瘤大小[ < 3 cm vs. >3 cm;危险度（HR）=0.406;95%可信区间（95%CI）:0.202~0.816;P= 0.011]、体力状态评分（ < 2 vs. >2;HR=0.113;95%CI:0.202-0.631;P=0.013）、混合性非小细胞肺癌（NSCLC）成分（LCNEC vs.非LCNEC成分,HR=3.00;95%CI:0.096~0.483;P < 0.001）、病理分期（ⅢA期vs. Ⅰ期;HR=0.195,95%CI:0.063-0.602;P=0.004）及辅助治疗（是vs.否,HR=0.402;95%CI:0.195~0.831;P=0.014）为C-SCLC患者预后影响因素。  结论  混合型小细胞肺癌中的大细胞神经内分泌肿瘤成分会显著影响患者生存;术后辅助治疗明显有益于C-SCLC术后患者生存率的提高。      

倾向评分匹配法探讨预后营养指数与乳腺癌患者术后预后的关系

目的探讨预后营养指数(PNI)与乳腺癌患者术后预后的关系。方法选取2009年1月至2014年8月在溧阳市人民医院住院并接受改良根治术治疗的乳腺癌患者173例。以PNI=45为临界值，分为PNI<45组及PNI≥45组，采用倾向评分匹配法对组间差异进行平衡。匹配完成后两组各有63 例进入模型。采用多因素COX回归模型分析影响乳腺癌患者术后生存的独立影响因素。结果倾向评分匹配后,PNI <45乳腺癌患者的中位生存期(43个月)低于PNI≥45组(50个月)(P=0003)。多因素COX回归分析显示,绝经后(HR: 1,62; 95％CI:129～204)、TNM Ⅲ期(HR: 188; 95％CI:144～246)、PNI<45(HR: 147; 95％CI:122～178)是影响乳腺癌患者术后生存的独立风险因素。结论PNI可以独立影响乳腺癌的生物学行为,PNI较低的患者术后死亡风险增加。     

克唑替尼在ALK阳性晚期NSCLC患者中的疗效和安全性评价及其预后影响因素

目的 探讨克唑替尼在间变性淋巴瘤激酶(ALK)阳性晚期非小细胞肺癌(NSCLC)患者中的疗效和安全性,并重点分析其预后影响因素.方法 收集2013年1月至2016年9月在北京协和医院就诊且经细胞学或组织学证实的晚期(ⅢB ～Ⅳ期)ALK阳性NSCLC患者50例,记录相关临床信息、治疗方案并随访疗效和安全性,分析预后影响因素.结果 截至随访结束,进展患者(24例)中位无进展生存期(PFS)为9.6个月(95％ CI为8.3 ～10.9个月),其中5例死亡;未进展患者(26例)中位随访时间为10.7个月.最常见的不良反应为肝功能异常(48.0％,24/50);在Kaplan-Meier单因素分析中,≤40岁的患者拥有更长的PFS(P =0.017),且COX回归多因素分析(Enter法)也有意义(HR =6.1,95％ CI为1.4～27.5,P=0.018);而性别(HR =0.8,95％ CI为0.2～2.6,P=0.697)、吸烟史(HR=1.5,95％ CI为0.4 ～5.6,P=0.524)、病理类型(HR=1.1,95％ CI为0.3 ～4.2,P=0.922)、分期(HR=1.7,95％ CI为0.4 ～8.4,P=0.502)、表皮生长因子受体(EGFR)突变型(HR =0.4,95％ CI为0.4 ～4.3,P=0.461)、EGFR未知(HR=1.3,95％ CI为0.3～6.1,P=0.727)、美国东部肿瘤协作组体能状态评分(HR =2.0,95％ CI为0.6 ～6.8,ECOG PS评分,P=0.290)、既往治疗情况(HR =0.6,95％ CI为0.2～1.8,P=0.385)和脑转移情况(HR =0.7,95％ CI为0.1 ～3.2,P=0.628)均与疾病进展时间无关.结论 克唑替尼对晚期ALK阳性NSCLC患者有良好的疗效,安全可耐受,年龄是其预后的独立影响因素.     

术后辅助化疗对Ⅰ期非小细胞肺癌无瘤生存时间的影响

背景与目的 手术是早期肺癌的首选治疗方法,但早期肺癌术后的预后仍有很大差异,术后是否应用辅助化疗也有争议.本研究探讨术后辅助化疗在Ⅰ期非小细胞肺癌患者中的作用,尤其是在高危人群中的作用.方法 选择北京大学人民医院2009年1月-2013年6月接受手术的Ⅰa期、Ⅰb期肺癌患者,分别以是否行术后化疗分为两组,用Kaplan-Meier法进行生存分析,比较两组术后无瘤生存时间(disease-free survival,DFS)的差异;并按危险因素个数进行评分,分为0分、1分、≥2分三组,比较三组术后DFS的差异;单独比较术后化疗对≥2分的高危组患者的作用.结果 经过筛选后共有465例患者纳入研究,Ⅰa期284例,Ⅰb期181例.Ⅰa期化疗组和对照组术后DFS并无明显差异(P=0.171),但化疗组生存曲线位于对照组下方,Ⅰb期两组术后DFS也无明显差异(P=0.630).危险因素评分后的三组患者DFS有明显差异(P<0.001),危险因素越多,术后DFS越差,可看作是高危患者.但单独分析显示,术后化疗与否对这部分高危患者的DFS并无显著影响(P=0.763).结论 术后化疗对早期非小细胞肺癌的DFS并无积极作用,即使是对于具有多个高危因素的I期非小细胞肺癌患者,术后化疗也许也不适用.     

ⅠB期和ⅡA期宫颈癌患者的预后因素分析

目的 探讨影响ⅠB期和ⅡA期宫颈癌预后的高危因素。方法 1992年12月-2001年12月手术治疗的111例宫颈浸润癌,中位年龄40岁。按FIGO(1994)分期标准,ⅠB期80例(ⅠB1期和ⅠB2期各40例),ⅡA期31例。鳞癌93例(8318％),腺癌17例(15.3％),小细胞癌1例。111例患者均采用广泛性子宫切除加以撕剥式为主的盆腔淋巴清扫术,术前辅助放疗74例(66.7％),术后辅助治疗24例(21.6％)。生存率统计采用Kaplan-Meier方法,预后相关因素分析采用Cox模型和x^2检验。结果 全组患者5年生存率为85.9％,其中ⅠB1期为89.1％,ⅠB2期为90.7％,HA期为78.4％。经单因素分析显示,肿瘤大小(HR=1.479,P=0.152)、肿瘤局部类型(HR=1.440,P=0.264)、临床分期(HR=1.380,P=0.354)、术前和(或)术后辅助治疗(HR=1.210,P=0.450)、淋巴结转移(HR=1.432,P=0.540)、颈管受侵(HR=2.244,P=0.036)、深肌层浸润(HR=3.295,P=0.06)和多个性伴侣 合并妊娠(HR=10.172,P=0.000)与早期宫颈癌预后有关。经多因素分析显示,宫颈深肌层浸润和多个性伴侣 合并妊娠是影响预后的重要因素。结论 宫颈深肌层浸润和多个性伴侣 合并妊娠与早期宫颈癌预后密切相关,对具有高危因素的ⅠB期和ⅡA期宫颈癌患者应加强术前和(或)术后的辅助治疗。     

不同基因分型晚期非小细胞肺癌患者的预后分析

背景与目的 非小细胞肺癌(non-small cell lung cancer,NSCLC)已由原来的组织分型指导下的治疗转变为基因分型指导治疗的模式,表皮生长因子受体(epidermal growth factor receptor,EGFR)和间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)是肺癌最重要的两个驱动基因.本研究旨在探讨不同基因分型的复发或转移晚期NSCLC患者的临床特点及预后影响因素.方法 回顾性分析北京胸科医院2004年7月-2015年12月间553例EGFR和ALK基因状态明确的晚期NSCLC患者的临床资料,采用Cox比例风险回归模型对患者预后的独立影响因素进行分析.结果 553例细胞学或组织学证实的晚期NSCLC患者,EGFR突变患者227例,ALK阳性患者58例,EGFR和ALK双突变患者2例,EGFR和ALK野生型患者266例.227例EGFR突变患者的中位生存期(overall survival,OS)为28.7个月(95%CI:22.160-35.240),体能状态(performance status,PS)评分为0分-1分(HR=4.451;95%CI:2.112-9.382;P<0.001)、接受EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)靶向治疗(HR=2.785;95%CI:1.871-4.145;P<0.001)是EGFR突变患者生存的独立影响因素.58例ALK阳性患者的中位OS为15.5个月(95%CI:10.991-20.009),接受克唑替尼靶向治疗(P=0.022)是ALK阳性患者生存的独立影响因素.266例野生型患者的中位OS为12.1个月(95%CI:10.660-13.540),PS评分为0分-1分(HR=2.313;95%CI:1.380-3.877;P=0.001)、接受化疗(HR=1.911;95%CI:1.396-2.616;P<0.001)是野生型患者生存的独立影响因素.结论 不同基因型的晚期NSCLC患者的预后差异较大,靶向治疗可改善EGFR突变、ALK阳性患者生存.     

小细胞肺癌患者预后的多因素分析

背景与目的综合治疗是改善小细胞肺癌预后的关键。本研究旨在回顾性分析小细胞肺癌患者的预后因素。方法1999年1月~2005年6月,收治一般情况良好(PS=0、1)、经综合治疗(化疗+放疗±手术)且资料完整的253例小细胞肺癌患者,采用Kaplan-Meier法绘制生存曲线,寿命表法计算生存率,COX多因素回归比例风险模型分析患者的预后因素。结果中位随访23.2月(3~85月)。全组患者1年、3年、5年生存率分别为77.9%、33.8%和23.3%,其中局限期为88.3%、40.2%和31.2%,广泛期为62.9%、22.0%和8.8%。全组中位生存时间为23月(95%CI19~27月),其中局限期为27月,广泛期为15月。单因素分析发现性别(P=0.0395)、分期(P=0.0000)、治疗初LDH水平(P=0.0000)、手术与否(P=0.0029)、治疗初是否有体重减轻(P=0.0000)以及一线化疗疗效(P=0.0000)等因素可影响患者的生存。多因素分析结果提示,性别(P=0.019)、LDH升高(P=0.000)、手术(P=0.024)和体重下降(P=0.006)是影响患者生存的独立预后因素。结论对一般行为状态好的小细胞肺癌患者,经综合治疗后,性别、LDH升高、手术和体重下降是影响其预后的主要因素。     

大姚县青石棉污染区恶性肿瘤死亡27年回顾性队列研究

目的:研究生产和生活性青石棉暴露与恶性肿瘤死亡之间的关系.方法:利用1984年在云南省大姚县青石棉污染区建立的含1 249例健康人群的回顾性队列,通过COX等比例风险模型计算青石棉接触时间以及生产风炉、原料处理、刷墙、砌灶和浆衣等过程中的青石棉暴露对恶性肿瘤死亡的风险比( hazard ratio,HR)及其95％可信区间(confidence interval,CI).结果:截至2011年4月30日,队列中共有121例恶性肿瘤死亡病例.调整年龄、性别、婚姻、文化程度、吸烟和饮酒等混杂因素后,与接触期限≤5年相比,青石棉接触6～10年的HR=2.898(95％CI:1.496～5.616)、11～15年的HR=4.159 (95％CI:2.169～7.975)、＞15年的HR=4.233 (95％CI:1.182～9.886),且有显著的剂量-反应关系(Ptrend＜0.05);与不生产风炉相比,零星生产风炉的HR=2.533(95％CI:1.549～4.142),成批生产风炉的HR=2.541(95％CI:1.642～3.935);与不处理原材料相比,机器粉碎原材料HR=1.811 (95％CI:1.211～2.709),人工粉碎原材料HR=1.785 (95％CI:1.072～2.793);刷墙4次以上HR=1.736 (95％CI:1.000～3.012);砌灶HR=2.229(95％CI:0.97～5.122);浆衣HR=3.307(95％CI:1.522～7.184).结论:生产和生活性青石棉接触均可增加恶性肿瘤的死亡风险.     

肺癌合并静脉血栓栓塞症89例临床分析

目的:本研究旨在探讨肺癌合并静脉血栓栓塞症(venous thromboembolism,VTE)患者的临床相关因素,为肺癌合并VTE的预防及治疗提供依据。方法:对2008年7月-2010年6月收治的经细胞学或病理学确诊的2053例肺癌病例进行回顾性分析。采用螺旋CT、肺动脉造影及彩色多普勒超声检查明确VTE诊断。将年龄、性别、病理类型、肺癌分期、手术、体质量指数、基础疾病、治疗前血小板计数、D-二聚体、白细胞介素1和肿瘤坏死因子作为临床相关因素。结果:2053例肺癌患者中,89例(4.34%)患者合并VTE。腺癌患者的VTE发生率为5.65%(58/1027),非腺癌患者为3.02%(31/1026),差异有统计学意义(P=0.003);Ⅰ～ⅢA期患者的VTE发生率为1.48%(10/677),ⅢB～Ⅳ期患者的VTE发生率为5.74%(79/1376),差异有统计学意义(P<0.001);Ⅰ～ⅢA期接受手术治疗患者的VTE发生率为1.55%(10/645),未行手术治疗患者的VTE发生率为0%(0/32),差异有统计学意义(P=0.044);无基础疾病患者的VTE发生率为2.70%(33/1221),伴随基础疾病患者的VTE发生率为6.73%(56/832),差异有统计学意义(P<0.001)。治疗前,血小板计数、D-二聚体、白细胞介素1和肿瘤坏死因子水平正常者的VTE发生率分别为3.72%、0.31%、2.44%和3.27%,而水平升高者的VTE发生率分别为6.26%、19.91%、10.26%和7.74%,差异均有统计学意义(P<0.05)。Logistic多因素回归分析显示,腺癌、手术、基础疾病以及D-二聚体、白细胞介素1和肿瘤坏死因子水平升高是肺癌患者发生VTE的相关临床因素(P<0.05)。结论:肺癌合并VTE患者中,腺癌是最常见的病理类型。手术、基础疾病以及D-二聚体、白细胞介素1和肿瘤坏死因子水平升高是肺癌患者发生VTE的危险因素。     

Preoperative plasma D-dimer levels predict survival in patients with operable non-small cell lung cancer independently of venous thromboembolism

Background and aims

D-dimer is a stable end product of fibrin degradation that is associated with advanced tumor stage and poor prognosis in lung cancer patients. Venous thromboembolism (VTE) is a frequent complication of cancer and is associated with a poor prognosis in cancer patients. The purpose of the study is to elucidate whether the increased mortality in non-small cell lung (NSCLC) patients with elevated D-dimer levels is independent of VTE.

Patients and methods

A retrospective review was conducted of 232 patients with operable NSCLC from January 2007 to June 2008. All the patients underwent a pneumonectomy, lobectomy or wedge resection. We assessed the ability of preoperative plasma D-dimer levels to predict 1-year mortality and overall survival among them, and a multivariable Cox proportional-hazard regression analysis was performed after controlling for the following potential confounding factors: age, gender, TNM stage, histology, tumor size, VTE and surgical interventions.

Results

The overall 1-year survival rate was 91.4% (95% confidence interval (CI), 82.7–94.8%), with a 76.5% survival (95% CI, 71.4–81.6%) in the high D-dimer group and a 93.9% survival (95% CI, 86.4–97.9%) in the normal D-dimer group. Comparing the high D-dimer group with the normal D-dimer group, the adjusted hazard ratio for 1-year mortality and overall survival was 3.19 (95% CI, 1.18–7.12) and 1.54 (95% CI, 1.11–2.78) respectively.

Conclusion

Our study concluded that the preoperative plasma D-dimer level is an important prognostic biomarker in patients with operable NSCLC that is independent of VTE.     

Venous thromboembolism and survival in patients with high-grade glioma

Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were followed after surgery until October 2005. Objectively confirmed VTE was recorded as an event. All patients had received thrombosis prophylaxis with low-molecular-weight heparin (LMWH) during the immediate postoperative period. Subsequently, 56 patients received radiochemotherapy, 6 radiotherapy, and 1 chemotherapy only. Patients were followed over a median time period of 348 days. Fifteen patients (24%) developed VTE. Pulmonary embolism was diagnosed in nine patients (60%) and was fatal twice. The cumulative probability of VTE was 21% after three months and 26% after 12 months. The highest frequency of VTE was observed in patients with biopsy and subtotal tumor resection (n = 37; multivariate hazard ratio, 3.58; 95% CI = 0.98-13.13; P = 0.054) compared with patients with total resection. Survival did not significantly differ among patients with and without VTE and was 53% after 12 months in both groups. Patients with HGG, particularly those with biopsy and subtotal resection, are at high risk to develop VTE postoperatively. Thrombosis was not associated with a significant reduction of survival.     

Novel High-Sensitive D-Dimer Determination Predicts Chemotherapy-Associated Venous Thromboembolism in Intermediate Risk Lung Cancer Patients

IntroductionWe hypothesized that the use of a novel high sensitivity (HS) assay for D-dimer determination might ameliorate venous thromboembolism (VTE) risk prediction in intermediate risk lung cancer patients in whom chemotherapy could act as a trigger for VTE onset.Patients and MethodsPretreatment HS D-dimer levels were retrospectively evaluated in 108 lung cancer outpatients using a novel automated latex enhanced turbidimetric immunoassay. All patients were at the start of a new platinum-based chemotherapy regimen and were classified as intermediate risk according to Khorana's assessment model. Patients were followed-up for a median period of 6.9 months.ResultsReceiver operating characteristic (ROC) curves and corresponding Bayesian analysis showed that the best performance was obtained at a cutoff level of 1500 ng/mL, which resulted in a sensitivity of 81%, a specificity of 69%, a positive predictive value (PPV) of 31%, a negative predictive value (NPV) of 96%, and an accuracy of 70%. Patients with HS D-dimer levels above the cutoff had a worse VTE-free survival (60%) compared with those with levels below the cutoff (95%; P = .0001). Multivariate Cox proportional hazards survival analysis confirmed that pretreatment HS D-dimer levels were able to significantly predict VTE with a hazard ratio of 11 (95% confidence interval, 2.62-46.2; P = .001), independently of classic VTE risk factors.ConclusionsThe use of HS D-dimer determination prior to chemotherapy might allow for VTE risk stratification of intermediate risk cancer patients, helping in identifying those individuals who could benefit from thromboprophylaxis.     

Comparison of the Efficacy and Safety of EFGR TyrosineKinase Inhibitor Monotherapy with Standard Second-line Chemotherapy in Previously Treated Advanced Non-small-cell Lung Cancer: a Systematic Review and Meta-analysis

Purpose: To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinaseinhibitormonotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agentdocetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC). Methods: Wesystematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standardsecond-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS),progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals(CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the includedtrials. Results: Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis resultsshowed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC interms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall responserate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysisdemonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03)and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OSand 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia andneutrotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash. Conclusion: Both interventions hadcomparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapywas associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFRTKImonotherapytended to be more effective in East Asian patients in terms of PFS and ORR compared withstandard second-line chemotherapy. These results should help inform decisions about patient management anddesign of future trials.     

Prevalence and Clinical Significance of Incidental and Clinically Suspected Venous Thromboembolism in Lung Cancer Patients

BackgroundIt is unclear what proportion of VTE events in lung cancer patients are incidentally discovered and whether incidental events affect mortality.Patients and MethodsWe conducted a retrospective cohort study of lung cancer patients seen at the University of Rochester between January 1, 2006 and December 31, 2008 with the goal of quantifying and characterizing VTE events. Multiple clinical variables and mortality outcomes were compared using Kaplan-Meier survival analysis and multivariate Cox proportional hazards.ResultsThe study population consisted of 207 subjects with lung cancer. The median age was 66 years and 55% were female (n = 115). Thirty-one patients (14.9%) experienced at least 1 VTE event with 32.2% (10/31) of these incidentally discovered. Incidental events comprised 29.4% (n = 5) of pulmonary embolisms, 11.1% (n = 2) of deep vein thrombosis, and 100% (n = 3) of visceral events. The median survival for patients with incidental VTE was 23.4 months (95% confidence interval [CI], 4.8-32.1) compared with 45.8 months (95% CI, 34.1-56.8) in patients without VTE (HR 2.4; 95% CI, 1.2-4.9; P = .01), but in a subgroup analysis of stage IV patients overall survival was not significantly different (HR, 0.94; P = .33). Patients with clinically suspected VTE had the lowest median survival at 13.1 months (95% CI, 6.4-18.9) which was significantly lower than patients without VTE (HR, 2.7; 95% CI, 1.6-4.5; P = .002), but not significantly different from patients with incidental VTE (HR, 1.2; 95% CI, 0.4-2.0; P = .7). In multivariate analysis, occurrence of VTE (HR, 2.3; 95% CI, 1.3-3.8; P = .002) was significantly associated with mortality when adjusting for age, stage, and histology.ConclusionsOne-third of VTE events in lung cancer patients are incidentally discovered and VTE has negative clinical effect in lung cancer patients.     

EGFR-TKIs治疗术后复发肺腺鳞癌患者的临床研究

  目的  分析表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors，EGFR-TKIs）治疗术后肺腺鳞癌（adenosquamous carcinoma of the lung，ASC）患者的疗效。  方法  回顾性分析2006年1月至2014年12月上海交通大学附属胸科医院诊治的ASC 205例，采用描述性分析及Kaplan-Meier法进行生存分析。  结果  筛选出27例EGFR突变并接受TKIs治疗的ASC患者，其中15例患者存在19号外显子缺失突变，12例患者存在21号外显子点突变。临床疗效方面，9例患者部分缓解（partial response，PR），11例患者疾病稳定（stable disease，SD），疾病控制率（disease control rate，DCR）为74.1%。生存分析结果显示，术后中位生存时间为39.0个月（95% CI:25.6~52.4），中位无进展生存时间为15.0个月（95% CI:12.9~17.1），3、5年生存率分别为51.9%、15.3%。  结论  具有EGFR敏感突变的ASC患者能够从TKIs治疗中获益，推荐对ASC患者进行常规EGFR基因突变检测，实现个体化、多学科治疗以改善患者预后。      

The efficacy of combination of EGFR TKIs and chemotherapy versus EGFR TKIs monotherapy for first-line treatment of NSCLC with EGFR mutation: A Meta-analysis北大核心CSCD

Objective: To investigate the clinical value of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. Methods: Retrieval of PubMed, EMBASE, Web of Science and other databases from the start of the database building to 2017 was conducted to search randomized controlled trial of EGFR-TKI combined with chemotherapy vs EGFR-TKI single drug first-line treatment of EGFR mutant NSCLC. Meta-analysis was performed. The primary end point was progression-free survival (PFS), the secondary end points were objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 4 articles were included in this analysis, with a total of 353 patients. Compared with EGFR-TKI monotherapy, EGFR-TKI in combination with chemotherapy significantly prolonged PFS [hazard ratio (HR) = 0.65, 95% confidence interval (CI): 0.50-0.84, P= 0.001], as well as in subgroups of EGFR 19 deletion, L858R point mutation, age 5=65 years, performance status (PS) score was 1, female and never smoker (all P < 0.05). However, the combination group did not show significant differences in ORR and DCR compared with EGFR-TKI monotherapy group [relative risk (RR) = 1.07, 95% CI: 0.94-1.22, P = 0.282; RR = 1.02, 95% CI: 0.96-1.08; P = 0.531]. The combined regimen caused more fatigue, nausea and leukopenia (RR = 2.64, 95% CI: 1.32-5.25, P = 0.006; RR = 6.87, 95% CI: 3.06-15.45, P < 0.001; RR = 10.02, 95% CI: 3.18-31.55, P < 0.001). There were no differences in adverse reactions more than grade 3 between two groups (all P > 0.05). Conclusion: The combination of EGFR-TKI and chemotherapy can prolong the PFS compared with EGFR-TKI alone for the first-line treatment of NSCLC with EGFR mutation, and the adverse reactions were tolerable. Copyright © 2018 by TUMOR. All rights reserved.     

术前预后营养指数对Ⅰ期非小细胞肺癌术后复发的预测价值

目的 探讨术前预后营养指数对Ⅰ期非小细胞肺癌术后复发的预测价值.方法 对178例NSCLC患者的临床资料进行回顾性研究.随访并记录所有患者的临床资料,包括性别、年龄、吸烟史、手术方式、病理类型、T分期、TNM分期、肿瘤最大直径、血管浸润、淋巴管浸润、脏层胸膜浸润、化疗次数、PNI值等资料.应用Cox单因素和多因素回归分析对影响NSCLC患者的危险因素进行分析.结果 随访时间3~5年,术后复发28例,复发率15.7%.178例患者的中位生存时间为(49.5±13.6)个月,1、3、5年生存率分别为83.7%、75.3%、70.2%.单因素分析显示:手术方式(χ2=6.982,P=0.004)、TNM分期(χ2=5.814,P=0.021)、血管浸润(χ2=5.942,P=0.019)、脏层胸膜浸润(χ2=7.912,P=0.001)、化疗次数(χ2=6.715,P=0.006)及PNI值(t=7.413,P=0.003),均为NSCLC患者预后复发的影响因素.经过Cox多因素预后复发危险分析结果显示:手术方式(HR=1.034,95%CI:0.726~1.513,P=0.009)、化疗次数(HR=0.301,95%CI:0.182~0.454,P=0.001)和PNI值(HR=0.2.314,95%CI:1.61~2.92,P=0.000)是影响NSCLC患者预后复发的独立危险因素.结论 PNI指数是预测I期非小细胞肺癌患者术后复发的独立危险因素,PNI值与I期非小细胞肺癌患者术后复发几率呈正比.     

肺腺癌根治术后复发与转移的预后因素分析

目的 探讨肺腺癌根治术后局部复发与远处转移的危险因素.方法 收集2005年1月至2010年1月新疆医科大学第一附属医院收治的102例接受肺叶切除肺腺癌病例,对影响其预后的临床病理因素进行单因素及多因素分析,采用Kaplan-Meier绘制生存曲线,采用Log-rank检验单因素统计学差异,采用COX回归比例风险模型对预后影响因素进行多因素分析.结果 全组1、2、3、5年无瘤生存率分别为74.30％、58.00％、51.50％、44.90％,总的中位无瘤生存期为30个月.单因素分析结果显示,肿瘤直径(x2=9.951,P=0.002)、临床类型(χ2=8.460,P=0.004)、肿瘤分化程度(χ2=4.807,P=0.028)、淋巴结转移情况(χ2=40.516,P=0.000)、病理分期(x2 =38.769,P=0.000)是影响肺腺癌患者根治术后局部复发和远处转移的预后因素.多因素分析结果显示,肿瘤直径(OR=1.943,95％ CI为1.091～3.463,x2 =5.082,P=0.024)、肿瘤分化程度(OR =2.570,95％ CI为1.451～4.552,x2=10.467,P=0.001)、淋巴结转移情况(OR=3.196,95％ CI为1.037～9.849,x2 =4.096,P=0.043)是影响患者术后局部复发和远处转移的独立预后因素.结论 对于肺腺癌根治术的患者,肿瘤直径、肿瘤分化程度、淋巴结转移情况是独立的预后因素.     

Current views on the role of Notch signaling and the pathogenesis of human leukemia

Background

Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^nd EGFR-TKI administration.

Methods

We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.

Results

Three patients (27%) were treated with gefitinib as the 2^nd EGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^nd EGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^nd EGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^nd EGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.

Conclusions

Our results indicate that a 2^nd EGFR-TKI treatment can be an effective treatment option for gefitinib responders.