消癌平注射液联合间断化疗治疗老年晚期非小细胞肺癌

目的 观察消癌平注射液联合间断化疗治疗老年晚期非小细胞肺癌患者的疗效及毒副反应.方法 将老年晚期非小细胞肺癌患者74例随机分为2组,对照组37例应用多西他赛＋奥沙利铂方案连续化疗,观察组37例应用多西他赛＋奥沙利铂方案的同时,给予消癌平注射液.观察2组患者近期疗效、生活质量、中位生存期及毒副反应.结果 有效率观察组和对照组分别为32.4%和24.3%,差异有统计学意义（P〈0.05）;生活质量改善率观察组为75.6%,高于对照组的54.0%（P〈0.05）;中位生存期观察组388 d,长于对照组的243 d（P〈0.05）;毒副反应发生率观察组低于对照组（P〈0.05）.结论 消癌平注射液联合间断化疗治疗晚期非小细胞肺癌,可以提高患者的近期疗效、改善生存质量和延长生存期,安全性好.     

The Rationale for Adjuvant Chemotherapy in Stage I Non-small Cell Lung Cancer

The past decade has witnessed renewed interest in studies exploring the benefits of adjuvant (postoperative) chemotherapy (± radiation therapy) in patients with resected non-small cell lung cancer (NSCLC). Recently completed adjuvant trials have included a heterogeneous group of patients with resected stages I to IIIA NSCLC. With rare exception, the published results of these studies indicate adjuvant chemotherapy imparts a significant overall survival advantage. Subset analyses suggest survival benefit occurs primarily in patients with resected stage II or IIIA and is less likely to occur in stage I patients. This apparent lack of survival benefit in stage I patients was seemingly validated in a prospective trial conducted by the Cancer and Leukemia Group B in which stage IB patients were randomized to observation or adjuvant carboplatin and paclitaxel. Survival at 5 -years was identical in the two arms of this trial. By contrast, two contemporary postoperative chemotherapy trials also conducted exclusively in stage I NSCLC patients yielded positive survival results. The divergent outcome of the prospective trials along with the negative subset analyses has created uncertainty as to the utility of postoperative adjuvant chemotherapy in stage I NSCLC. Herein we review the data underlying this controversy and offer a proposed algorithm to aid the clinician in selecting patients whom we believe may benefit from adjuvant chemotherapy. The treatment algorithm is based on currently available tumor- and host-related factors that affect prognosis.     

RASSF1A和p16 转录本在非小细胞肺癌中的表达及启动子区甲基化

 目的 研究RASSF1A和p16基因在国人非小细胞肺癌（NSCLC）组织中的转录及启动子区甲基化情况，探讨其转录失活的机制，为NSCLC的诊断和治疗寻找新的途径。方法 应用半定量RTPCR和甲基化特异性PCR法分析96例NSCLC及远癌正常肺组织中RASSF1A和p16基因mRNA的表达和启动子区甲基化情况。结果 （1）53．12％（51／96）的NSCLC中RASSF1A表达明显下调或缺失；36．46％（35／96）的p16表达下调或缺失，而远癌正常肺组织均表达良好。（2）96例NSCLC中RASSF1A甲基化率48．96％（47／96），该基因表达明显下调或缺失的51例中39例（76．5％）出现甲基化，表达正常的45例中8例（17．8％）出现甲基化，两组对比差异有统计学意义（P〈0．05）；96例NSCLC中33例（34．38％）检测到p16启动予区甲基化，p16基因表达明显下调的35例中20例（57．1％）出现该基因CPG岛的甲基化，而表达正常的61例中13例（21．3％）出现甲基化，两组比较差异显著（P〈0．05）。96例远癌正常肺组织均未检测到此两基因启动子有甲基化。结论 RASSF1A和p16基因mRNA在国人NSCLC中较高比例的表达下调或缺失；甲基化可能是两基因表达失活的主要原因。     

Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation groupl (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lungcancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistrywas applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancerparaffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic valueof the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used todetermine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%,36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with thesurvival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negativecancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positivealone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter thanthose with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.     

Quantitative Assessment of the Diagnostic Role of CDH13 Promoter Methylation in Lung Cancer

In order to explore the association between cadherin 13 (CDH13) gene promoter methylation and lungcarcinoma (LC) risk, we carried out a meta-analysis with searching of PubMed, Web of Science. Ultimately,17 articles were identified and analysised by STATA 12.0 software. Overall, we found a significant relationshipbetween CDH13 promoter methylation and LC risk (odds ratio=6.98, 95% confidence interval: 4.21-11.56,p<0.001). Subgroup analyses further revealed that LC risk was increased for individuals carrying the methylatedCDH13 compared with those with unmethylated CDH13. Hence, our study identified a strong association betweenCDH13 gene promoter methylation and LC and highlighted a promising potential for CDH13 methylation inLC risk prediction.     

ⅢA期非小细胞肺癌新辅助化疗的病理组织学效应及其预后的影响

目的研究新辅助化疗诱导ⅢA期非小细胞肺癌(NSCLC)组织病理学反应对患者预后的影响。方法 40例患者完成2个周期新辅助化疗后,19例(47．5％)获客观缓解,其中完全缓解2例(5％),部分缓解17例(42．5％)。40 例ⅢA期NSCLC患者接受2个周期的新辅助化疗后手术,化疗方案由丝裂霉素、长春地辛和顺铂组成。手术后检查切除肿瘤标本的组织病理学反应。肿瘤组织对化疗的反应根据肿瘤坏死程度和残留肿瘤组织范围分为Ⅳ级、Ⅲ级、Ⅱ级和Ⅰ级。评价患者生存期与肿瘤组织对化疗反应等级之间的关系。结果40例患者的肿瘤切除标本中．2例(5％)属Ⅳ级,16例(40％)为Ⅲ级,18例(45％)为Ⅱ级,4例为Ⅰ级。肿瘤组织反应为Ⅲ -Ⅳ级患者的手术完全性切除率明显高于Ⅰ-Ⅱ级患者(P<0．05),中位生存期亦显著长于Ⅰ-Ⅱ级患者(P<0．05)。肿瘤组织反应属Ⅲ-Ⅳ级患者的3年生存率与Ⅰ-Ⅱ级患者比较明显为长(P<0．05)。结论由新辅助化疗诱导的肿瘤组织反应程度是ⅢA期NSCLC患者获成功治疗的关键因素。化疗后肿瘤切除标本上,有明显肿瘤组织反应(Ⅲ-Ⅳ级反应)存在提示患者预后较好。     

新辅助化疗对局部晚期非小细胞肺癌术后生存率的影响

目的探讨新辅助化疗对局部晚期非小细胞肺癌生存率的影响。方法可切除的局部晚期非小细胞肺癌119例;分两组：新辅助化疗+手术组（A组）59例,直接手术组(B组) 60例。对两组患者的临床资料进行统计学分析。结果A组的总有效率为54.23%（32/59）,病期下调率20.33%（12/59）;手术切除率和完全性切除率分别为91.5％和81.4％,高于对照组为81.7％和68.3％。两组患者术后1、3、5年生存率分别为79.66%、50.88%、21.43%和71.19%、35.09%、14.29%,两者比较差异有统计学意义(P<0.05);术后平均生存时间分别为32.909月和28.046月,差异有统计学意义(P<0.05),而术后并发症发生率两组比较差异无统计学意义(P>0.05)。结论新辅助化疗可显著提高局部晚期非小细胞肺癌的手术切除率,延长生存期,较直接手术组有优势,且未增加术后并发症,是安全可行的。     

Association of RASSF1A Promoter Methylation with Lung Cancer Risk: a Meta-analysis

RASSF1A, regarded as a candidate tumor suppressor, is frequently silenced and inactivated by methylation ofits promoter region in many human tumors. However, the association between RASSF1A promoter methylationand lung cancer risk remains unclear. To provide a more reliable estimate we conducted a meta-analysis ofcohort studies to evaluate the potential role of RASSF1A promoter methylation in lung carcinogenesis. Relevantstudies were identified by searches of PubMed, Web of Science, ProQest and Medline databasesusing thefollowing key words: ‘lung cancer or lung neoplasm or lung carcinoma’, ‘RASSF1A methylation’ or ‘RASSF1Ahypermethylation’. According to the selection standard, 15 articles were identified and analysised by STATA12.0 software. Combined odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength ofthe association between RASSF1A promoter methylation and lung cancer risk. A chi-square-based Q test andsensitivity analyses were performed to test between-study heterogeneity and the contributions of single studiesto the final results, respectively. Funnel plots were carried out to evaluate publication bias. Overall, a significantrelationship between RASSF1A promoter methylation and lung cancer risk (OR, 16.12; 95%CI, 11.40-22.81;p<0.001) with no between-study heterogeneity. In subgroup analyses, increased risk of RASSF1A methylation incases than controls was found for the NSCLC group (OR, 13.66, 95%CI, 9.529- 19.57) and in the SCLC group(OR, 314.85, 95%CI, 48.93-2026.2).     

单药健择与联合方案治疗老年晚期非小细胞肺癌的临床观察

目的　评价单药健择与健择联合顺铂治疗老年晚期非小细胞肺癌的临床疗效与不良反应。方法　选用 48例老年晚期非小细胞肺癌 (NSCLC)患者 ,单药组 2 7例 ,采用健择 1.0 /m2 静脉点滴 ,第 1,8,15天 ;联合方案组 2 1例 ,采用健择 1.0 /m2 静脉点滴 ,第 1,8天加顺铂 (DDP) 75mg/m2 静脉点滴第 1～ 3天。结果　单药组有效率 2 9.6% ( 8/2 7) ,联合治疗组 47.6% ( 10 /2 1) ,有显著差异 (P <0 .0 1) ,联合治疗组不良反应率较单药组高。结论　单药健择不仅疗效较好 ,不良反应轻 ,而且有效提高老年患者生存质量及用药安全性。     

非小细胞肺癌的治疗进展

全文综述了近年来非小细胞肺癌手术、化放疗临床治疗上的一些进展，并就可能出现的新的治疗模式作一展望。     

肺癌血清p16基因启动子畸变甲基化检测

[目的]检测肺癌患者血清DNA中p16基因启动子畸变甲基化,并探讨其在肺癌早期诊断和预后评价中的作用。[方法]收集新鲜的肺癌组织及其对应的血清标本69例,肺良性疾病患者标本25例,健康人血清标本10例。采用PCR技术分别检测肿瘤组织DNA和血清游离DNA中p16基因启动子畸变甲基化的状况。[结果]28.99%(20/69)肺癌组织出现p16高甲基化;出现高甲基化的组织标本相对应的20例血清中有15例(75%)出现p16基因高甲基化。肺良性疾病患者及正常人的血清、DNA中均未见p16基因高甲基化。血清p16基因高甲基化与肺癌TNM分期及分化程度密切相关(P<0.01或P<0.05)。[结论]非小细胞肺癌血清中p16基因甲基化状况的检测,可能有助于非小细胞肺癌的早期诊断或预后评估。     

ⅢA期非小细胞肺癌新辅助化疗的病理组织学效应及其预后的影响

Objective： To investigate prognostic impact of histopathologic response induced by neoadjuvant chemotherapy in patients with stage ⅢA non-small cell lung cancer （NSCLC）. Methods： Forty patients with stage ⅢA NSCLC underwent two cycles of neoadjuvant chemotherapy with mitomycin, vindosine, and cisplatin followed by surgery. Histopathologic response in resection of the tumor was examined after surgery. Tumor regression was classified as grade Ⅳ, grade Ⅲ, grade Ⅱ, and grade Ⅰ according to the extent of tumor necrosis and the extent of the vital tumor tissues. The tumor regression grading was correlated with the survival time of the patients. Results： After two cycles of chemotherapy, 19 （47.5%） of 40 patients had objective response （2 complete and 17 partial response）. In 40 resected tumor specimens, 2 （5%） were classified as regression grade Ⅳ, 16 （40%） as regression grade Ⅲ, 18 （45%） as regression gradeⅡ, and 4 （10%） as regression grade Ⅰ. The rate of complete surgical resection was significantly higher in patients with tumor regression grade Ⅲ-Ⅳ （〈10% vital tumor tissue）（P〈0.05）. The median survival time in patients classified as having tumor regression grade Ⅲ-Ⅳ was significantly longer than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. The 3-year survival rate in patients with regression grade Ⅲ-Ⅳ was markedly higher than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. Conclusion： The extent of tumor regression induced by neoadjuvant chemotherapy is a critical issue for successful therapeutic approach in patients with stage ⅢA NSCLC. In resected specimens of tumors after chemotherapy, the presence of marked tumor regression （regression grade Ⅲ-Ⅳ） is predictive for superior survival time.     

Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer

Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1)were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) werecorrelated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivityand clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatinregimens. Materials and Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinicalresponse was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessedby 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents). Results:There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequencydistribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive grouphad higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the jointdetection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + higheffective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicityshowed no correlation with the genotypes between two groups (p>0.05). Conclusions: Compared with singledetection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may bemore helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy.Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict theresponse and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.     

卡铂为主化疗同步结合放射治疗非小细胞肺癌

[目的]观察卡铂为主的化疗方案同步结合放射治疗非小细胞肺癌(NSCLC)的临床疗效.[方法]选择NSCLC患者100例随机进入放化疗同步治疗组和放疗化疗序贯治疗组,两组病例均给予常规放疗,同步组放疗开始的1、4、8、12周给予化疗(卡铂加氟尿嘧啶);序贯组在放射治疗结束后给予4个周期的化疗(卡铂、丝裂霉素加长春新碱).[结果]同步组和序贯组的近期疗效有效率分别为82%和64%;1、3、5年生存率、中位生存期分别为76%、32%、15.7%、28个月和62%、22%、9.9%、18.6个月,两组差异有显著性(x2=4.373,P＜0.05).两组患者的毒副反应主要为可逆性骨髓抑制、放射性食管炎和放射性肺炎,两组发生率相似.[结论]卡铂为主的化疗同步结合放射治疗NSCLC效果好于放疗后化疗的序贯治疗.     

Down-regulation and Clinic-pathological Correlation of SIK-1 and SIK-1-LNC in Non-small Cell Lung Cancer Patients

Background: Non-small-cell lung cancer (NSCLC) is currently the leading cause of mortality cancer. Introducing noninvasive approaches to diagnose NSCLC, especially at an early phase, might improve the disease’s prognosis. Long noncoding RNAs (lncRNAs), which are important regulators of the expression genes inside the cells, have been linked to a range of biological processes, such as cancer progression and metastasis, including NSCLC. The present work aims to determine the potential involvement of SIK-1-LNC and SIK-1 in NSCLC pathogenesis and the possible use of these molecules as novel biomarkers or therapeutic targets. Methods: In this work, the expression levels of SIK-1-LNC and SIK-1 in 50 pairs of NSCLC tumor and tumor marginal tissues were evaluated. So, after total RNA extraction and complementary DNA synthesis, the SIK-1-LNC and SIK-1 expression levels were evaluated by real-time PCR. In the study groups, clinical and pathological characteristics of the NSCLC patients were also examined. Results: Our findings showed that tumor samples had much lower levels of SIK-1 and SIK-1-LNC expression than tumor margin samples. SIK-1-LNC expression was correlated with SIK-1 levels in NSCLC samples. Interestingly, both stage and lymph node metastasis features of the tumor were associated significantly with SIK-1 and SIK-1-LNC expression levels. A ROC curve analysis indicated a biomarker index of 0.69 and 0.74 for SIK-1 and SIK-1-LNC, respectively. Conclusion: Collectively, our study emphasized the role of SIK-1-LNC and SIK-1 downregulation in NSCLC oncogenesis. Additionally, SIK-1 and SIK-1-LNC, particularly the latter, have shown remarkable potential to be utilized as new NSCLC biomarkers and therapeutic targets.     

GP方案联合三维适形放疗同步治疗局部晚期非小细胞肺癌

目的探讨GP方案联合三维适形放疗同步治疗局部晚期非小细胞肺癌（NSCLC）的近期疗效和毒副反应。方法 30例局部晚期NSCLC患者采用GP方案联合三维适形放疗同步治疗。结果 30例患者均完成治疗计划,肺原发灶及纵隔转移淋巴结总有效率分别为83.4%和88.5%;毒副反应主要是骨髓抑制,胃肠道反应,轻中度放射性食管炎、放射性肺炎。结论 GP方案联合三维适形放疗同步治疗局部晚期NSCLC具有较好近期疗效及耐受性。     

含泰素两药联合方案治疗晚期非小细胞肺癌的对比观察

[目的]探讨含泰素两药联合化疗方案治疗晚期非小细胞肺癌的疗效与毒性.[方法] 50例经病理或细胞学证实的Ⅳ期非小细胞肺癌,采用泰素-表阿霉素(TE组)和泰素-顺铂(TP组)的联合化疗方案作对比观察.TE组:泰素120～150mg/m2,静滴,第1天;表阿霉素50～70mg/m2,静注,第1天.TP组:顺铂25mg/m2,静滴,d1～3,泰素用法同TE组,每21～28天为1个周期,用泰素前均行预处理.[结果]疗效:TE组和TP组分别为PR各12例,SD 3例和4例,PD 10例和9例,两组均无CR病例,各组有效率48%.两组中位生存期(MST)、中位疾病进展期(MTTP)均分别为8、7个月.全部病例有效者中位生存时间13个月,无效者中位生存时间4.5个月(3～5个月),有显著性差异(P＜0.05).毒性反应:两组均是以骨髓抑制为主要的毒性反应,也是剂量限制性毒性,TE组较TP组明显,其中Ⅲ～Ⅳ度分别为72%和36%.非血液学毒性以消化道反应为主,恶心或呕吐较为常见,但均能经对症处理缓解.[结论]含泰素为基础的两药联合化疗方案对晚期非小细胞肺癌有较好的疗效,同等条件下择泰素联合铂类较优;毒性反应以血液学毒性为主,且系药物剂量限制性毒性.     

晚期非小细胞肺癌不同化疗方案的疗效比较

目的 比较顺铂分别联合紫杉醇,吉西他滨,长春瑞滨治疗晚期非小细胞肺癌的近期疗效和毒副反应.方法 60例晚期非小细胞肺癌随机分为3组,TP组16例,GP组23例,NP组21例,比较3种方案的疗效及其毒副反应的差异.结果 3种方案有效率分别为:TP组为43.8%,GP组为43.5%,NP组为42.9%,无显著性差异(P＞0.05);3组患者生活质量获益率分别为:TP组为81.3%,GP组为82.6%,NP组为81.0%,无显著性差异(P＞0.05);毒副反应中,3组间白细胞减少,恶心、呕吐发生率无显著性差异(P＞0.05); TP组神经毒性发生率明显高于其他2组,差异有显著性(P＜0.05);GP组血小板下降明显高于其他2组,差异有显著性(P＜0.05);NP组静脉炎发生率明显高于其他2组,差异有显著性(P＜0.05);3组的肝、肾功能损害发生率差异无显著性(P＞0.05).结论 TP、GP、NP方案疗效近似,毒副反应各异,但均可耐受.临床用药遵循个体化原则.     

A Pooled Study on Combination of Gemcitabine and Nedaplatin for Treating Patients with Non-small Cell Lung Cancer

Background: This analysis was conducted to evaluate the efficacy and safety of a combination of gemcitabineand nedaplatin in treating patients with non-small cell lung cancer. Methods: Clinical studies evaluating theefficacy and safety of a combination of gemcitabine and nedaplatin with attention to response and safety forpatients with non-small cell lung cancer were identified using a predefined search strategy. Pooled responserates for gemcitabine and nedaplatin were calculated. Results: In gemcitabine and nedaplatin based regimens, 4clinical studies including 112 patients with non-small cell lung cancer were considered eligible for inclusion. Thepooled analysis suggested that the pooled reponse rate was 40.2% (45/112). Main side effects included grade 3-4neutropenia, thrombocytopenia, and anemia. Grade 3-4 nonhematological toxicity included nausea and vomiting,diarrhea, and hepatic dysfunction. There were no treatment-related deaths. Conclusion: This evidence basedanalysis suggests that the combination of gemcitabine and nedaplatin is associated with good response rate andaccepted toxicity for treating patients with non-small cell lung cancer.