LRP及GST-π的表达与非小细胞肺癌的耐药性关系

 目的探讨NSCLC的化疗耐药性和参与介导多药耐药的相关基因和蛋白LRP及GST-π的表达,对比分析NSCLC的多药耐药性与上述二种耐药相关基因表达的关系。方法应用肿瘤细胞体外培养和MTT法对91例未经化疗的NSCLC进行体外化疗药物敏感性测试,观察NSCLC分别对环磷酰胺、阿霉素、顺铂+5-Fu三种单药和联合用药方案耐药情况和总的耐药情况,并用免疫组织化学方法对其进行3种耐药相关基因(LRP、MRP及GST-π)表达的检测,并将其表达情况与对应的化疗耐药性进行相关分析。结果91例NSCLC化疗敏感性检测结果显示:53例(58.2%)对环磷酰胺耐药,51例(56.0%)对阿霉素耐药,42例(46.2%)对顺铂+5-Fu耐药。其中,19例(20.9%)对三种用药均敏感,27例(29.8%)对三种用药均耐药,其耐药性与组织学类型和分化程度无关(P>0.05)。LRP和GST-π在91例NSCLC中总的阳性表达率分别为:53.8%和64.8%。鳞癌和腺癌相比LRP和GST-π的表达无显著性差异(P>0.05)。且LRP和GST-π的表达与对三种化疗用药的耐药性均呈显著正相关(P<0.05),并且不同表达程度间也有显著...     

外周血细胞分析与NSCLC晚期患者预后的相关性

目的探讨外周血淋巴细胞相对计数和血小板计数与NSCLC晚期患者预后的关系。方法用χ2检验和KaplanMeier生存曲线分析NSCLC晚期死亡患者的外周血淋巴细胞相对计数、血小板计数、生存时间以及和预后的相关性。结果淋巴细胞分类计数≤20%组,中位生存期2个月;淋巴细胞分类计数>20%组,中位生存期6个月。血小板计数≤250×109/L组,中位生存期4个月;血小板计数>250×109/L组,中位生存期3个月,组间均具有显著性差异(P<0.005)。通过KaplanMeier生存曲线和logrank检验,其生存率差异显著。结论血小板增多和淋巴细胞相对计数减少,都是影响NSCLC晚期病人预后不良的重要因素。     

淋巴结清扫及采样在临床N0期NSCLC手术中的意义

目的：研究临床分期为N0的NSCLC术后淋巴结转移情况与术后生存率之间的差异，探讨临床分期为N0的NSCLC纵隔淋巴结清扫或采样的必要性。方法：回顾1985年1月～2000年6月手术切除的术前判断为N0的手术病例，对比术后淋巴结转移情况，判断术前cTNM与pTNM的偏差，以及患者生存率的变化。结果：本组cTNM分期总的准确率为42．32％（201／475），临床Ⅰ期的NSCLC（cT1N0M0、cT2N0M0）中出现N1或N2淋巴结转移的病例（pT1N1M0、pT1N2M0、pT2N1M0、pT2N2M0）与未出现转移的病例（pT1N0M0、pT2N0M0）之间的生存率之间差异显著，P〈0．01。本组cT3N0M0与pT3N1M0、p％N2M0之间生存率差异不明显。结论：尽管临床Ⅰ期的NSCLC（cT1N0M0、cT2N0M0）临床上无淋巴结转移证据，但由于临床分期与术后病理分期客观上存在差异，淋巴结清扫及采样仍是必要的，任何不能行淋巴结清扫的肿瘤局部治疗方法都可能是不充分的。     

含顺铂方案治疗老年晚期非小细胞肺癌的安全性及可行性(附122例病例报告)

目的　探讨老年晚期非小细胞肺癌 (NSCLC)含顺铂方案化疗的安全性与可行性。方法　对6 6例晚期NSCLC老年患者 (≥ 6 0岁 )及 5 6例中青年晚期NSCLC患者的近期疗效、毒副作用等临床资料进行分析 ,以及比较老年晚期NSCLC组中顺铂不同剂量用法的疗效及毒副作用。结果　老年组有效率37 9% ,临床获益率 86 38% ,中青年组有效率 33 9% ,临床获益率 85 7% ,两组比较差异无显著性 ;在血液、肾、肝、胃肠道毒性等方面两组差异无显著性。老年组中高剂量顺铂与常规剂量顺铂多日使用组在中性粒细胞减少 ,血小板减少 ,肾毒性及肝毒性等毒副作用方面 ,高剂量组出现较多的Ⅲ /Ⅳ度毒副作用 ,其差异有显著性 ;而近期疗效相似 ,差异无显著性。结论　老年晚期NSCLC患者在机体状况良好 ,无明显并发症情况下 ,可接受含常规剂量顺铂的联合化疗方案 ,安全有效性较好。     

Locally Advanced Non-small Cell Lung Cancer: The Past,Present, and Future

Approximately a third of patients with newly diagnosed non-small cell lung cancer (NSCLC) have locally or regionally advanced disease not amenable for surgical resection. Concurrent chemoradiation is the standard of therapy for patients with unresectable locally advanced NSCLC who have a good performance status and no significant weight loss. Prospective studies conducted over the past two decades have addressed several important questions regarding systemic therapy and thoracic radiation. They include the role of induction/consolidation chemotherapy, integration of newer chemotherapy agents with radiation and the impact of molecularly targeted agents. Improved radiation therapy techniques and precise targeting of the tumors have played a key role in this setting. Moreover, it has been shown that higher than conventional doses of thoracic radiation can be administered safely in combination with chemotherapy. This review will discuss these issues in detail and outline the strategies that need to be employed to improve the outcomes in patients with locally advanced NSCLC.     

Afatinib in NSCLC With HER2 Mutations: Results of the Prospective,Open-Label Phase II NICHE Trial of European Thoracic Oncology Platform (ETOP)

IntroductionMutations in erb-b2 receptor tyrosine kinase 2 (HER2) oncogene are observed in approximately 3% of lung adenocarcinomas or mixed tumors with adenocarcinoma component. Activity of various biologically distinct HER2 inhibitors, including the pan-HER inhibitor afatinib, has been reported in several retrospective trials or small series in advanced pretreated NSCLC with HER2 mutations. We report the first prospective evaluation of afatinib for the treatment of this molecularly defined entity.MethodsNICHE, a single-arm phase II trial using a two-stage Simon’s design, explored the potential of afatinib to control disease in pretreated patients with advanced NSCLC harboring HER2 exon 20 mutations. A total of 13 patients entered the trial and were treated with afatinib 40 mg/day until tumor progression or lack of tolerability.ResultsThe first-stage stopping boundary was crossed when five of nine patients did not achieve disease control at 12 weeks. The accrual into the trial was stopped with total 13 patients enrolled, with 7 (53.8%) achieving disease control at 12 weeks. Except for 1 patient with early death, progression was documented for all patients, with median progression-free survival of 15.9 weeks (95% confidence interval: 6.0–35.4), and median overall survival of 56.0 weeks (95% confidence interval: 16.3– upper limit not estimable). The toxicity profile was in the expected range.ConclusionsAfatinib did not show the expected potential for disease control in NSCLC. However, more than half of the patients in the full cohort achieved disease control at 12 weeks.     

Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation–Positive Advanced NSCLC: Findings From a Global Named Patient Use Program

Introduction

Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for this subgroup.

Role of Postoperative Radiotherapy in the Management for Resected NSCLC – Decision Criteria in Clinical Routine Pre- and Post-LungART

BackgroundThe role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer.MethodsTwenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed.ResultsFollowing decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors.ConclusionAfter presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT.     

Safety and Clinical Activity of Atezolizumab Plus Ipilimumab in Locally Advanced or Metastatic Non–Small Cell Lung Cancer: Results From a Phase 1b Trial

BackgroundThis phase 1b study investigated safety and activity of combined checkpoint inhibition (CPI) with programmed death-ligand 1 (PD-L1) antibody atezolizumab plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in NSCLC.Patients and MethodsEligible patients had previously treated locally advanced or metastatic non–small cell lung cancer (NSCLC) or melanoma. A standard 3+3 dose escalation investigated atezolizumab (600-1200 mg IV every 3 weeks) plus ipilimumab starting at 1 mg/kg, administered as a single dose or 4 doses, administered every 3 weeks. The expansion stage included a cohort previously treated with atezolizumab. Patients were monitored for safety and tolerability; response was evaluated every 6 weeks.ResultsTwenty-seven patients were enrolled, 4 with melanoma and 23 with NSCLC; here, we focus on data for the NSCLC population. Three of 23 patients (13.0%) received prior CPI. No dose-limiting toxicities were reported during dose escalation; dose expansion occurred with atezolizumab 1200 mg plus 1 cycle of ipilimumab 1 mg/kg. Most common treatment-emergent adverse events were dyspnea (39%) and cough (35%); treatment-related Grade ≥3 adverse events occurred in 11 patients (48%), most frequently pneumonitis (17%) and amylase or lipase elevation (9% each). Six of 23 NSCLC patients (26%) achieved confirmed responses, 5 of whom (25%) were CPI naive. Median duration of response was 23.0 (95% CI, 3.2-36.9) months overall and 36.9 (95% CI, 2.9-36.9) months in CPI-naive patients.ConclusionPreliminary efficacy of atezolizumab plus ipilimumab was observed in metastatic NSCLC. The combination had manageable toxicity, with a safety profile consistent with those of the individual agents.     

非小细胞肺癌人群中c-MET基因的扩增检测

目的：c-MET基因扩增是非小细胞肺癌对EGFR TKIs（吉非替尼或厄罗替尼）产生耐药的主要机制之一。本研究探讨没有接受TKIs治疗与TKIs治疗后耐药的NSCLC中c-MET基因的扩增是否存在差异。方法:获得55例术后非小细胞肺癌（NSCLC）的肿瘤组织（基线组）以及23例对TKIs耐药的肿瘤组织（耐药组）后,通过激光显微切割筛选癌细胞后提取基因组DNA,实时荧光定量PCR TaqMan探针法检测所有标本的c-MET基因的拷贝数。 结果:1.基线组和耐药组的临床病理特征均与c-MET基因的扩增无关。2.基线组中c-MET基因扩增阳性率为5.5% (3/55);耐药组的c-MET基因扩增阳性率为21.7% (5/23)。两组之间有统计学差异（Fisher精确概率法,P=0.045）。3.在7例获得TKI治疗前后肿瘤组织的NSCLC中,TKI治疗前没有出现c-MET的基因扩增,TKI治疗后有2例患者出现了c-MET的基因扩增（2/7）。TKI治疗前后的c-MET基因扩增差异无统计学意义。结论:NSCLC的临床病理特征不能预测c-MET基因扩增;在没有接受EGFR TKIs治疗的NSCLC中,c-MET基因扩增仅为少见事件。但经过吉非替尼或厄罗替尼治疗后出现耐药情况NSCLC中,部分患者的c-MET基因出现扩增。     

吉西他滨联合顺铂治疗老年晚期非小细胞肺癌研究

目的比较吉西他滨联合顺铂方案对老年非小细胞肺癌和非老年非小细胞肺癌的疗效和毒副作用的区别。方法 采用吉西他滨联合顺铂3周方案治疗晚期老年非小细胞肺癌35例, 同期非老年35例作为对照, 观察近期疗效和毒副作用。结果 老年组伴随疾病发生率、化疗前评分及完成化疗周期数较非老年组为高;有效率45.7%∶51.4%, 中位生存时间9.0月∶9.2月, 一年生存率38.2%∶40.6%均无显著性差异;毒副作用也无显著性差异。结论 吉西他滨联合顺铂3周方案对于老年非小细胞肺癌是一个比较安全的选择。     

MGMT表达与非小细胞肺癌化疗疗效和预后关系的研究

目的　研究MGMT在非小细胞肺癌 (NSCLC)组织中的表达情况及其与NSCLC患者化疗疗效和预后的关系。方法　应用免疫组化S P法检测正常肺组织及肿瘤组织中的MGMT表达。将 12 8例NSCLC组织分为Mer-组 (MGMT表达阴性 )和Mer+ 组 (MGMT表达阳性 )。结果　 12 8例NSCLC中阳性表达率为 47.66% ( 61/ 12 8) ,而 10例正常肺组织中未见MGMT表达。MGMT表达与肺癌患者性别、年龄、肿瘤分期、淋巴结转移、组织类型等临床生理病理特征均无明显关系。Mer-组术后平均生存期及生存率均较Mer+ 组明显延长 (P <0 .0 1,P <0 .0 5 )。 45例可评价疗效的病例中 ,Mer-组总的化疗有效率为 42 .86% ( 9/2 1) ,Mer+ 组为 4.17% ( 1/ 2 4) (P <0 .0 0 1) ;Mer-组生存期和生存率明显高于Mer+ 组 (P <0 .0 1,P <0 .0 5 )。结论　MGMT表达水平可以作为临床预测NSCLC患者化疗疗效和预后的有意义的指标。     

Navelbine治疗晚期肺癌的Ⅱ期临床研究报告

1992年7月至1993年2月,用NAVELBINE治疗35例Ⅲ—Ⅳ期的非小细胞肺癌患者,所有病例均经病理组织学证实,包括鳞癌12例,腺癌18例、肺泡癌3例、腺样囊腺瘤和大细胞癌各1例。实际可评价的病人34例,其中Navelbine单药治疗16例(25mg/m~2/周×4),5例PR,有效率为31.3％。联合治疗(Navelbine+CDDP)18例,CR1例(5.6％)PR8例(44.4％),总有效率为50％。主要毒性为骨髓抑制,白细胞减少Ⅲ—Ⅳ级发生率为32.4％,其中一例高龄者白细胞严重减少,合并败血症而死亡。该研究提示,Navelbine对非小细胞肺癌的治疗价值是肯定的,主要剂量限制毒性为骨髓抑制,应在肿瘤学专家的指导下使用。     

Cetuximab治疗非小细胞肺癌的进展

表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)患者中存在过表达.Cetuxumab(C225,erbitux)是一种单克隆抗体,可竞争性结合EGFR细胞外配体区,抑制肿瘤生长,与放化疗有协同作用.本文综述cetuxumab联合放化疗治疗晚期NSCLC的临床前和临床资料,显示出cetuxumab具有良好耐受性.     

长春瑞滨加顺铂、吉西他滨加顺铂治疗晚期非小细胞肺癌临床疗效及毒副反应对比观察

目的 评价长春瑞滨(NVB)与顺铂(DDP)及吉西他滨(GEM)与顺铂联合化疗治疗晚期非小细胞癌(NSCLC)的疗效及毒副作用.方法 选择62例不能手术的晚期非小细胞肺癌病人,随机分为2组,分别采用NP(NVB DDP)方案及GP(GEM DDP)方案治疗.结果 NP和GP组有效率分别为46.9%(15/32)vs46.7%(14/30),两者无显著差异,分析诸多因素对疗效的影响发现,初治比复治疗效好,病期早比病期晚疗效好,鳞癌比腺癌疗效好.骨髓抑制为剂量限制性毒性,NP组为100%,GP组为90.0%,非血液学毒性主要表现为恶心呕吐,NP组发生率81.3%,GP组86.7%,NP组局部静脉炎发生率为59.4%.结论 NP及GP方案治疗晚期非小细胞肺癌疗效好,毒副反应可以耐受,值得在临床上推广应用.     

化疗对非小细胞肺癌患者生存质量的影响

目的探讨非小细胞肺癌患者化疗前后生存质量的变化。方法使用肺癌患者生存质量量表FACT-L中文版（V4.0）,分别在化疗前3天、化疗后1周及化疗后3个月对134例非小细胞肺癌患者进行生存质量问卷调查。结果生存质量总体评分化疗后1周较化疗前显著下降（P〈0.05）,化疗后3个月较化疗前提高,但无统计学意义（P〉0.05）,其中化疗有效者生存质量较化疗前显著提高（P〈0.01）,化疗无效者生存质量虽较化疗前提高,但无统计学意义（P〉0.05）。结论化疗期间患者的生存质量下降,主要为化疗的毒副作用所致,化疗后3个月患者的生存质量得到改善,化疗是否有效对生存质量的改善更为重要。     

吉非替尼治疗晚期非小细胞肺癌

目的评价吉非替尼作为二线和二线以上方案治疗晚期非小细胞肺癌(NSCLC)的临床价值。方法符合入组条件的156例患者采用吉非替尼治疗,口服,每天1次,每次250mg,持续服用直到疾病进展或出现不可耐受的毒副反应。结果154例患者可评价疗效,总有效率(RR)为28.6%(44/154),95% CI为21.6%～31.6%;临床受益率为89.6%(138/154),95% CI为84.8%～94.4%。有效患者的中位缓解时间为7.5个月(95% CI为3.9～12.1个月),中位肿瘤进展时间(TTP)为5.1个月(95% CI为3.4～6.6个月),中位总生存期(OS)为10个月(95% CI为7.9～12.1个月),1年生存率为41.0%(95% CI为33.3%～48.7%)。腺癌患者的有效率显著高于鳞癌患者(P=0.026)。其中,鳞癌患者肿瘤进展的风险是腺癌的1.7倍(95% CI为1.1～2.6,P=0.011);男性死亡的风险是女性的2.0倍(95% CI为1.0～2.6,P=0.002)。154例患者中,63例(40.9%)患者至少出现了一种药物相关毒副反应,但多数较轻,且可逆,发生率最高的是皮疹(26.3%),多伴发皮肤干燥和瘙痒。结论吉非替尼作为二线及二线以上方案治疗晚期NSCLC有较好的疗效和安全性。     

p62在NSCLC组织中的表达及其与化疗效果的关系

目的 探讨自噬相关蛋白p62在非小细胞肺癌患者中的表达及其与化疗效果的关系.方法 选择60例确诊为NSCLC并接受联合化疗患者,并选择同期诊断为肺部良性疾病60例患者的外周血标本作为对照,采用免疫组化检测各组织标本中p62表达,ELISA检测患者外周血p62水平.结果 ①与对照组相比,NSCLC组p62高表达,化疗前后NSCLC患者外周血p62表达量及阳性表达率存在显著差异(P<0.05);②化疗有效者与无效者p62阳性率存在显著差异(P<0.05).结论 自噬相关蛋白p62在非小细胞肺癌呈高表达,且p62表达与NSCLC化疗效果有关,可作为NSCLC肿瘤指标及预测因子之一.