EGFR-TKIs治疗进展后停药与继续原药维持治疗晚期非小细胞肺癌的比较

摘 要：［目的］ 评价晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者小分子化合物酪氨酸激酶抑制剂治疗疾病进展后停药与继续靶向药物维持治疗的疗效。［方法］ 筛选既往口服厄洛替尼、吉非替尼或埃克替尼治疗有效后疾病进展的NSCLC患者162例,PS评分均>2分,无法耐受化疗者入组。治疗组患者继续原有小分子化合物维持治疗,对照组患者立即停用小分子化合物,观察疾病进展至死亡时间。 ［结果］ 治疗组大部分患者病情进展缓慢,少数患者维持稳定;而对照组大量患者病情加重,少量患者维持稳定状态。对照组的中位生存时间为4个月,而治疗组为6.2个月。治疗组继续服药一个月后以及对照组停药一个月后,治疗组的CEA含量显著低于对照组。对照组停止服药一个月后较停止服药初期血清中CEA含量显著升高;而治疗组继续用药一个月后,其CEA含量无明显变化。［结论］ 晚期NSCLC患者通过EGFR-TKI靶向治疗疾病进展后继续原小分子化合物维持治疗利于患者生存。     

血清CYFRA21 1、NSE、CEA、CA125及SCCA联合检测在肺癌诊断中的价值研究

目的探讨联合检测血清细胞角蛋白19片段(CYFRA21 1)、神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、糖类抗原125(CA125)、鳞状上皮细胞癌抗原(SCCA)对肺癌的临床诊断价值。方法选取2018年8月至2019年9月在安徽省胸科医院确诊的肺癌患者109例为肺癌组（腺癌61例,鳞癌30例,小细胞癌18例）,肺部良性疾病患者75例为良性肺病组,健康体检者49例为对照组。采用电化学发光法检测各组患者血清中CYFRA21 1、NSE、CEA、CA125及SCCA的表达水平。采用Kruskal Wallis检验、χ2检验比较各组血清CYFRA21 1、NSE、CEA、CA125、SCCA水平和阳性率,采用受试者操作特性曲线（ROC）分析上述5种肿瘤标志物对肺癌的联合诊断价值。结果肺癌组的血清CYFRA21 1、NSE、CEA、CA125、SCCA水平和阳性率明显高于良性肺病组和对照组;腺癌组血清CEA水平高于鳞癌组和小细胞癌组;腺癌组CEA阳性率高于鳞癌组;腺癌组SCCA阳性率高于小细胞癌组;鳞癌组SCCA水平和阳性率高于腺癌组和小细胞癌组;鳞癌组CYFRA21 1水平高于小细胞癌组（P<005）;小细胞癌组NSE水平和阳性率高于腺癌组和鳞癌组,差异均有统计学意义（P<005）。ROC曲线显示5种肿瘤标志物联合检测肺癌及不同病理分型肺癌的ROC曲线下面积（AUC）最大。结论肿瘤标志物CYFRA21 1、NSE、CEA、CA125、SCCA在不同病理分型肺癌中的表达各不相同,联合检测对不同病理分型肺癌的临床诊断价值更大。     

吉非替尼联合靶向EGFR DNA疫苗对小鼠Lewis肺癌细胞体内外的抑制作用

目的：探讨吉非替尼（gefitinib）联合靶向EGFR DNA疫苗对小鼠Lewis肺癌体内外的抑制作用。方法：用鸡EGFR与兔IgG Fc段异种融合DNA疫苗pVAX1/cEGFRrFc免疫小鼠制备抗血清,ELISA方法测定抗血清的效价。MTT法检测Lewis细胞的生长情况。建立Lewis肺癌鼠移植瘤模型,随机分为疫苗组、吉非替尼组、吉非替尼+疫苗组和对照组,观察各组小鼠肿瘤体积、重量及生存情况。结果：pVAX1/cEGFRrFc DNA疫苗免疫小鼠后抗EGFR血清效价为1∶1 000。与抗血清组或吉非替尼组相比,抗血清+吉非替尼组可显著抑制Lewis细胞的生长（P<0.05)。体内实验显示,吉非替尼+疫苗组小鼠移植瘤生长缓慢, 荷留小鼠生存率显著提高（P<0.01） 。结论：以EGFR为靶点的DNA疫苗和靶向药物吉非替尼之间具有协同性抗肿瘤作用,DNA疫苗主动免疫可以提高吉非替尼的疗效。     

三种肿瘤标志物在诊断恶性胸腔积液中的临床意义

 目的　探讨血清、胸腔积液中肿瘤标志物癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段抗原21-1 （CYFRA21-1）检测对恶性胸腔积液诊断的临床意义。方法　采用酶联免疫检测64例恶性胸腔积液（恶性组）和40例良性胸腔积液（良性组）患者的胸腔积液和血清中CEA、NSE、CYFRA21-1的水平,分析各指标单独及联合检测对恶性胸腔积液诊断的效能。结果　恶性组血清和胸腔积液CEA、NSE、CYFRA21-1测定值分别为（19.92±3.18）和（53.10±16.04）、（41.71±10.23）和（69.13±19.34）、（18.92±8.67）和（32.48±12.11）ng／ml,均高于良性组（0.35±0.47）和（0.35±0.57）、（1.53±0.55）和（4.01±1.22）、（3.18±0.94）和（3.59±1.48）ng／ml,差异有统计学意义（P＜0.05）。结论　CEA、NSE、CYFRA21-1肿瘤标志物测定在鉴别良恶性胸腔积液中有一定的价值。     

鸦胆子油乳注射液与吉非替尼联合治疗非小细胞肺癌的疗效及血清指标观察

目的 研究鸦胆子油乳注射液与吉非替尼联合治疗非小细胞肺癌(NSCLC)的疗效及对患者血清指标的影响.方法 按照治疗方式的不同将98例NSCLC患者分为对照组和观察组,每组49例.对照组使用吉非替尼治疗,观察组使用鸦胆子油乳注射液联合吉非替尼治疗.治疗4个周期后对比两组临床疗效,观察两组患者治疗前后血清肿瘤标志物[癌胚抗原(CEA)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、糖类抗原125(CA125)]及血清相关标志物[磷酸化细胞外信号调节激酶(p-ERK)、神经元特异性烯醇化酶(NSE)、血管内皮生长因子(VEGF)]水平的变化情况,统计两组患者治疗期间不良反应发生情况.结果 观察组总有效率为71.43％,明显高于对照组的36.73％,差异有统计学意义(P﹤0.01).治疗前,两组患者各项血清肿瘤标志物与相关标志物水平比较,差异均无统计学意义(P﹥0.05);治疗后,两组患者各项血清肿瘤标志物与相关标志物水平均低于本组治疗前,且观察组均低于对照组,差异均有统计学意义(P﹤0.05).两组不良反应总发生率比较,差异无统计学意义(P﹥0.05).结论 鸦胆子油乳注射液与吉非替尼联合治疗NSCLC,可获得更为良好的临床疗效,并能够进一步改善患者相关血清指标.     

吉非替尼联合抗凝方案治疗晚期非小细胞肺癌的疗效研究

目的 探讨吉非替尼联合抗凝方案治疗晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)的疗效。方法 收集晚期NSCLC患者70例，根据单双号分组，即对照组、治疗组，均35例。对照组采用传统化疗方案，治疗组在对照组的基础上采用吉非替尼联合抗凝方案。对比2组疗效。结果 治疗组患者临床总有效率为94.29%、疾病控制率为82.86%,均显著高于对照组(χ²=7.652,P=0.006;χ²=9.130,P=0.003)。治疗组血清肿瘤标志物CYFRA21-Ⅰ[(2.21±0.43)ng/ml]、CEA[(5.61±0.72)ng/ml]、SCC[(13.22±1.47)μg/ml]、NSE[(12.48±1.51)μg/L]水平均显著低于对照组(P<0.05)。治疗组不良反应发生率均显著低于对照组(P<0.05)。治疗组KPS评分为(80.31±6.21)分，显著高于对照组(P<0.05)。治疗组FIB[(3.66±1.26)g/L]显著低于对照组，TT[(18.19±1.14)s]显著高于对照组...     

非小细胞肺癌患者血清中组织蛋白酶S降解的巢蛋白-1检测的临床意义

摘 要：［目的］ 探讨非小细胞肺癌（NSCLC）患者血清中组织蛋白酶S降解的巢蛋白-1定量检测的临床意义。［方法］ 选择2010年1月至2012年12月来接受手术切除治疗的NSCLC患者48例,另选择同期年龄、性别48人正常人群作为对照。应用酶联免疫吸附法检测NSCLC患者及对照组中血清巢蛋白-1表达水平。应用单因素、多因素非条件Cox回归分析分析影响NSCLC患者预后的危险因素分析。［结果］ 48例NSCLC患者中血清巢蛋白-1表达水平为（105.62±25.67）ng/ml,显著性高于对照组的（34.59±8.26）ng/ml（P＜0.05）。NSCLC患者中血清巢蛋白-1表达水平与临床病理特征的关系结果显示,血清巢蛋白-1高表达与性别、年龄、吸烟史、嗜酒史、组织类型无相关性（P＞0.05）,与淋巴结转移、分化程度、TNM分期显著性相关（P＜0.05）。Kaplan-Meier生存分析结果显示,血清巢蛋白-1≤70ng/ml的NSCLC患者生存率显著性高于血清巢蛋白-1＞70ng/ml患者（P＜0.05）。多因素Cox回归分析结果显示,淋巴结转移、TNM分期、血清巢蛋白-1水平＞70ng/ml不利于NSCLC患者预后（P＜0.05）。［结论］ NSCLC患者中血清巢蛋白-1水平升高,血清巢蛋白-1水平可作为预测NSCLC患者预后的血清学标志物。     

吉非替尼在表皮生长因子受体突变晚期非小细胞肺癌患者中的应用效果

目的 探讨吉非替尼在表皮生长因子受体（EGFR）突变晚期非小细胞肺癌（NSCLC）患者中的应用效果。方法 根据治疗方法的不同将90例EGFR突变NSCLC患者分为对照组和观察组,每组45例,对照组患者接受化疗,观察组患者在对照组的基础上联合吉非替尼治疗。比较两组患者的临床疗效、血清肿瘤标志物[神经元特异性烯醇化酶（NSE）、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原（CEA）]水平、免疫功能指标[免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)]、炎性因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平及预后。结果 观察组患者的总有效率为68.89%,高于对照组患者的42.22%,差异有统计学意义（P<0.05）。治疗前,两组患者的NSE、CYFRA21-1、CEA、IgG、IgM、IgA、IL-6、TNF-α水平比较,差异均无统计学意义（P>0.05）。治疗后,两组患者的NSE、CYFRA21-1、CEA、IgG、IgM、IgA、IL-6、TNF-α水平均低于本组治疗前,观察组患者的NSE、CYFRA21-1、...     

血清肿瘤标志物对肺癌患者支气管镜活检病理组织学分型的预测价值

目的 探讨血清肿瘤标志物水平与支气管镜活检组织病理学分型的关系。方法 本研究纳入2013年1月—2018年12月于哈尔滨医科大学附属肿瘤医院行支气管镜下活检病理检查,且完成相关血清肿瘤标志物(SCCA、CYFRA21-1、CEA、CA125、NSE)检测的356例肺癌患者(140例小细胞癌、122例鳞状细胞癌、94例腺癌),对患者进行回顾性分析。结果 在支气管镜活检的肺癌患者中,五种血清肿瘤标志物的组合(SCCA+CYFRA21-1+CEA+CA125+NSE,AUC=0.948,P<0.001)对小细胞肺癌与非小细胞肺癌的辅助诊断价值更高;三种(SCC+CEA+NSE,AUC=0.901,P<0.001)或四种(SCC+CYFRA21-1+CEA+NSE,AUC=0.901,P<0.001)标志物联合鉴别鳞状细胞癌与腺癌准确性更高;而在非小细胞肺癌中鉴别鳞状细胞癌与腺癌,三种标志物组合(SCCA+CEA+CA125,AUC=0.831,P<0.001)的价值更高。结论 对于不同病理分型的肺癌患者,不同血清肿瘤标志物组合对支气管镜下活检病理的分型有一定的辅助诊断...     

应用ROC曲线评价PET/CT联合肿瘤标志物对肺癌的诊断效能

摘 要：［目的］ 探讨PET/CT联合血清肿瘤标志物检测在肺部良恶性占位病变的鉴别诊断价值。［方法］ 应用Logistic回归及ROC曲线回顾性研究228例肺部占位患者的临床资料。228例患者术前10天内完成PET/CT检查和血清肿瘤标志物（CEA、CA125、CYFRA21-1、NSE）检测,与病理结果对照,分别计算灵敏度、特异性、准确率、阳性预测值、阴性预测值;分析原发灶大小、TNM分期、病理类型与最大标准摄取值（SUVmax)的相关性。［结果］ 病理证实184例为肺癌、44例为良性病变。肿瘤标志物诊断肺癌的灵敏度、特异性、准确率、阳性预测值、阴性预测值分别为62.0%、72.7%、64.0%、90.5%、31.3%;PET/CT分别为94.6%、50.0%、86.0%、88.8%、68.8%;两者联合诊断肺癌灵敏度、特异性、准确率、阳性预测值、阴性预测值分别为98.4%、47.7%、88.6%、88.7%、87.5%,联合组的灵敏度及阴性预测值大于PET/CT组及肿瘤标志物组（P<0.05）。应用Logistic回归及ROC曲线比较肿瘤标志物、PET/CT组、联合组的曲线下面积（AUC）分别为0.759、0.760、0.822,联合组的诊断效能高于PET/CT及肿瘤标志物组。SUVmax与肺癌的病灶大小呈正相关（r=0.525,P=0.000）。［结论］ PET/CT联合血清肿瘤标志物检测有助于提高肺癌的诊断效能,SUVmax与肿瘤病灶大小呈正相关。     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs     

奥沙利铂联合羟基喜树碱治疗晚期胃癌临床分析

背景与目的体外及体内的临床研究显示,奥沙利铂(L-OHP)对多种肿瘤有显著抑制作用并与绝大多数抗癌药物具有相加或协同细胞毒作用.本文旨在观察L-OHP联合羟基喜树碱(HCPT)治疗晚期胃癌的近期疗效和患者耐受性,并与传统的化疗方案进行对比.方法采用非随机的分组方法将43例晚期胃癌患者分为L-OHP+HCPT方案组(治疗组)与Vp-16+CF+5-FU(ELF)方案组(对照组),其中男性28例,女性15例,中位年龄59岁,KPS评分≥60,观察两组的近期疗效和患者耐受性.结果治疗组24例有效率58.3%(14/24),对照组19例有效率42.1%(8/19).治疗组有效率高于对照组,两组差异有显著性(P<0.05).两组不良反应主要是骨髓抑制、恶心、呕吐、口腔炎、周围神经炎、静脉炎、脱发等,均在Ⅰ、Ⅱ度范围内.结论L-OHP联合HCPT方案治疗晚期胃癌疗效较好,不良反应可以耐受.     

Varicella-Zoster Virus Prophylaxis with Low-Dose Acyclovir in Patients with Multiple Myeloma Treated with Bortezomib

BackgroundVaricella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.Patients and MethodsWe studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m² was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.ResultsA total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.ConclusionVaricellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.