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.     

Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status.The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatmentoutcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospectiveanalysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy andreceived subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazardmodel for univariate and multivariate analyses was used to identify the baseline clinical parameters correlatingwith treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: Themedian treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including diseasestability for ≥3 months for 40% of the patients. Median progression-free survival and median overall survival(OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative OncologyGroup performance status (ECOG PS) ≥2 (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42;p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034)were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: Thisstudy suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessfulchemotherapy to improve treatment success, during which they should be monitored for intra-abdominalmetastasis and weight loss.     

Survival Analysis and Clinical Outcomes between Paclitaxel and Carboplatin Versus Carboplatin and Gemcitabine in Patients with Advanced-stage Non-small-cell Lung Cancer: A Single-center Cohort Study

Background: Palliative chemotherapy using platinum-based doublet chemotherapy was recommended as one of the standard treatments in patients with advanced-stage non-small cell lung cancer (NSCLC) with negative EGFR mutation. This study aimed to compare clinical outcomes between patients treated with paclitaxel and carboplatin (PC) and those treated with carboplatin and gemcitabine (CG). Methods: We conducted a retrospective cohort study comparing PC and CG at Hatyai Hospital between 2012 and 2019. The primary outcome was survival analysis, and the secondary outcome was chemotherapy-related adverse events, and the rate and reason for stopping chemotherapy.Result: The median overall survivals of both groups was comparable (9.0 months for the PC group and 9.6 months for the CG group; log-rank, p=0.287). The CG group had a higher incidence of adverse events (89.7% vs. 77.9%, p=0.010) and tended to have a lower rate of chemotherapy discontinuation (29.6% vs. 41.2%, p=0.080) than the PC group. In the multivariate analysis, female sex (odds ratio [OR]=0.351; 95% confidence interval [CI], 0.158-0.780; p=0.010) and higher performance status (OR=76.374; 95%CI, 32.533-179.295; p<0.001) were independent predictive factors for stopping chemotherapy. In the proportional hazards model, the factors associated with decreased survival included higher performance status (hazard ratio [HR]=1.939; 95%CI, 1.388-2.709; P<0.001) and discontinuation of chemotherapy (HR=2.572; 95%CI, 1.792-3.691; p=<0.001). Conclusion: These two platinum-based regimens had comparable effects on overall survival. The CG group had a higher incidence of chemotherapy-related adverse events, while the PC group had a marginally significantly higher rate of stopping chemotherapy from unacceptable adverse events and deterioration of patients’ clinical status.     

Lung Immune Therapy Evaluation (LITE) Risk,a Novel Prognostic Model for Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Blockade

Introduction/BackgroundImmune checkpoint inhibitors (ICI) have revolutionized non-small cell lung cancer (NSCLC). We aimed to identify baseline characteristics, that are prognostic factors for overall survival (OS) in patients with NSCLC treated with ICI monotherapy, in order to derive the Lung Immune Therapy Evaluation (LITE) risk, a prognostic model.Materials and MethodsMulti-center observational cohort study of patients with advanced NSCLC that received ≥1 dose of ICI monotherapy. The training set (n=342) consisted of patients with NSCLC who received first line ICI. The test set (n=153) used for external validation was a discrete cohort of patients who received second line ICI. 20 candidate prognostic factors were examined. Penalized Cox regression was used for variable selection. Multiple imputation was used to address missingness.ResultsThree baseline characteristics populated the final model: ECOG (0, 1 or ≥2), lactate dehydrogenase>upper limit of normal, and derived neutrophil to lymphocyte ratio ≥3. Patients were parsed into 3 risk groups; favorable (n=146, risk score 0-1), intermediate (n=101, risk score 2) and poor (n=95, risk score ≥3). The c-statistic of the training cohort was 0.702 and 0.694 after bootstrapping. The test cohort c-statistic was 0.664.The median OS for favorable, intermediate and poor LITE risk were; 28.3 months, 9.1 months and 2.1 months respectively. Improving LITE risk group was associated with improved OS, intermediate vs favorable HR 2.08 (95%CI 1.46-2.97, P < .001); poor vs favorable HR 5.21 (95%CI 3.69-7.34, P < .001).ConclusionA simple prognostic model, utilizing accessible clinical data, can discriminate survival outcomes in patients with advanced NSCLC.     

Comparison of Metabolic and Anatomic Response to Chemotherapy Based on PERCIST and RECIST in Patients with Advanced Stage Non-small Cell Lung Cancer

Background: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy,determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). Materials and Methods:Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) andprogression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CTprior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performedafter 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECISTand PERCIST, respectively. Results: The median OS and PFS were 11 months and 6.2 months, respectively. Atthe end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patientswho had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number ofcycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy accordingto the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapywas also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to fewpatients with anatomic response. In multivariate analyses, metabolic response after completion of therapy wasan independent prognostic factor for OS. Conclusions: Metabolic response is at least as effective as anatomicresponse in predicting survival. Metabolic response may be an earlier predictive factor for treatment responseand OS in NSCLC patients.     

全脑放疗时间对EGFR突变非小细胞肺癌脑转移患者生存的影响

背景与目的全脑放疗（whole brain radiotherapy, WBRT）在表皮生长因子受体（epidermal growth factor receptor,EGFR）突变的非小细胞肺癌（non-small cell lung cancer, NSCLC）脑转移患者治疗中何时应用尚无高级别的循证医学证据。本研究旨在探讨WBRT的参与时间对携有EGFR突变的NSCLC脑转移患者生存的影响。方法2009年8月-2015年5月在我院确诊的EGFR突变伴脑转移的晚期NSCLC共78例患者,均接受WBRT及EGFR酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitors, EGFR-TKIs）治疗的48例初治患者进入临床分析,采用Cox比例风险模型分析患者颅内无进展生存期（progression-free survival, PFS）及总生存期（overall survival, OS）的影响因素。结果全组患者颅内客观缓解率（objective response rate, ORR）为81.3%,颅内疾病控制率（disease control rate, DCR）为93.8%,中位颅内PFS为10个月,中位OS为18个月。颅内PFS的多因素分析显示,美国东部肿瘤协作组评分（Eastern Cooperative Oncology Group performance status, ECOG PS）0分-1分（HR=30.436,95%CI：4.721-196.211,P<0.001）及早期WBRT患者（HR=3.663,95%CI：1.657-8.098,P=0.001）的颅内PFS更佳。OS的多因素分析显示,ECOG PS 0分-1分（HR=57.607,95%CI：6.135-540.953,P<0.001）、早期WBRT（HR=2.757,95%CI：1.140-6.669,P=0.024）及立体定向放射外科（stereotaxic radio surgery, SRS）的应用（HR=5.964,95%CI：1.895-18.767,P=0.002）是患者OS的独立预后因素。结论早期WBRT联合TKIs治疗可改善EGFR突变的NSCLC脑转移患者的预后,尚有待大样本的前瞻性临床试验验证。     

联合奥沙利铂或顺铂二线治疗晚期非小细胞肺癌的临床研究

背景与目的：晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)二线化疗可选择单药多西他赛或培美曲塞,联合铂类能否提高疗效及延长生存尚不明确。本研究比较单药多西他赛或培美曲塞与联合奥沙利铂或顺铂方案二线治疗晚期NSCLC近期疗效、生存期和安全性。方法：经一线联合顺铂或卡铂治疗失败的121例晚期NSCLC患者按3∶2∶1比例随机分组,对照组(n=56)：多西他赛75 mg/m2(所有肺癌)或培美曲塞500 mg/m2(非鳞癌),第1天;顺铂组(n=45)：顺铂25 mg/m2,第1~3天联合多西他赛或培美曲塞;奥沙利铂组(n=20)：奥沙利铂130 mg/m2,第1天联合多西他赛或培美曲塞。3周为1个周期,治疗每个周期评价不良反应,每2个周期评价疗效,回访生存期。结果：3组的治疗疾病反应率、无进展生存期(progression free survival,PFS)、总生存期(overall survival,OS)及不良反应差异均无统计学意义(P＞0.05)。≥60岁老年患者较＜60岁患者PFS更长(HR=0.56,95%CI：0.35~0.90,P=0.015);PS评分0~1分患者PFS和OS更长(HR=1.52,95%CI：1.01~2.30,P=0.048;HR=1.90,95%CI：1.17~3.09,P=0.009)。治疗反应率与PFS和OS相关(HR=2.93,95%CI：2.01~4.26,P=0.000;HR=2.03,95%CI：1.37~3.01,P=0.000)。化疗后发生贫血患者PFS和OS呈缩短趋势(HR=1.59,95%CI：0.97~2.61,P=0.066;HR=1.60,95%CI：0.94~2.75,P=0.085),血小板减少患者OS更短(HR=2.97,95%CI：1.01~8.78,P=0.049)。有神经毒性患者PFS呈缩短趋势(HR=3.36,95%CI：0.92~12.25,P=0.066)。二线治疗失败后接受后续治疗者OS有获益(HR=0.36,95%CI：0.22~0.61,P=0.000)。结论：二线联合奥沙利铂或顺铂治疗NSCLC患者疗效和生存期无提高。疾病反应、PS评分与PFS及OS相关,治疗后发生贫血、血小板减少、神经毒性患者预后可能更差。二线治疗失败后接受后续治疗能延长生存期。     

80例ⅣB期血道转移宫颈鳞癌预后分析

目的 评估ⅣB期血道转移宫颈鳞癌的预后因素及盆腔根治性放疗的价值。方法 回顾性分析2006—2016年间在浙江省肿瘤医院接受治疗的ⅣB期血道转移宫颈鳞癌患者80例,并收集相关临床资料。采用Kaplan-Meier生存分析及Cox模型预后因素分析。结果 全组患者1、2、5年总生存(OS)率和无进展生存((PFS)率分别为52.5%、26.3%、16.8%和25%、13.8%、8.8%,中位OS和PFS期分别为13.0和5.6个月。最常见转移部位为骨(51.3%),其次为肺(36.3%)和肝(26.3%)。单因素生存分析显示化疗联合盆腔根治性治疗、化疗≥6个周期与OS及PFS呈正相关,而ECOG体能状态评分3~4分、肝转移与OS及PFS呈负相关。多因素分析显示肝转移(HR=2.23,95%CI为1.01~4.91,P=0.048)及体能状态评分3~4(HR=2.01,95%CI为1.03~3.91,P=0.040)为OS不利因素。亚组多因素分析显示化疗+盆腔根治性放疗比化疗±姑息放疗能改善患者OS (HR=0.39,95%CI为0.18~0.84,P=0.016),接受≥4个周期比<4个周期双药联合化疗能改善患者OS (HR=0.32,95%CI为0.15~0.68,P=0.003)。结论 体能状态不佳及肝转移患者预后不佳。在化疗基础上联合盆腔根治性放疗可改善ⅣB期血道转移宫颈癌患者的预后。     

105例晚期非小细胞肺癌预后因素分析

[目的]探讨晚期非小细胞肺癌（NSCLC）患者的预后相关因素。[方法]回顾性分析2003年1月1日至2009年12月31日105例晚期非小细胞肺癌死亡患者的临床资料,对可能影响其预后的相关因素进行单因素和多因素分析。[结果]全组患者1、2、3年生存率分别为27.6%、8.6%、1.9%,中位生存时间为9.0个月（95%CI：7.9～10.1个月）。单因素分析显示临床分期、PS评分、首诊伴脑转移、肝转移、骨转移以及治疗方式与预后相关。多因素分析显示临床分期、PS评分、首诊伴脑转移、治疗方式是影响晚期非小细胞肺癌预后的独立因素。[结论]临床分期、PS评分、首诊伴脑转移、治疗方式可能是晚期非小细胞肺癌患者的独立预后因素。     

Population characteristics and prognostic factors in metastatic non-small-cell lung cancer: a Fox Chase Cancer Center retrospective

PURPOSE: With the increasing use of magnetic resonance imaging and positron emission tomography for staging non-small-cell lung cancer (NSCLC), the demographics, performance status (PS), and distribution of metastases at diagnosis in this patient population are changing. We therefore reassessed the prognostic implications of baseline clinical variables in the modern era. PATIENTS AND METHODS: We retrospectively evaluated the charts of 172 consecutive, unselected patients aged 41-89 years (median, 62 years) with stage IV NSCLC monitored at the Fox Chase Cancer Center, a tertiary referral center, between October 2000 and August 2003. Cox proportional models were used to conduct univariate and multivariate analyses of baseline prognostic factors. RESULTS: Median age was 62 years; 79% of patients were PS 0/1 at first presentation. Fifty-six percent had single organ metastasis; 35% had brain metastases (one third had a solitary brain metastasis). Overall median survival was 10.4 months (95% CI, 8.1-13.6 months). The 1-, 2-, 3-, and 4-year survival rates were 44.2% (95% CI, 36.7%-51.4%), 21.9% (95% CI, 16%-28.3%), 11.6% (95% CI, 7.3%-17%), and 7.8% (95% CI, 4.2%-12.8%), respectively. On multivariate analysis, statistically significant negative prognostic factors included PS > or = 2 (hazard ratio [HR], 1.9 [95% CI, 1.1-3.28]), serum albumin of < or = 3 g/dL (HR, 1.7 [95% CI, 1.1-2.76 g/dL]), and metastases to > 1 organ (HR, 1.6 [95% CI, 1.03-2.3]). Brain, bone, and liver metastases were not found to be independent predictors of survival. CONCLUSION: The most important prognostic determinants were PS, baseline albumin, and number of metastatic sites. Incidence of brain metastases at presentation in this population was higher than usually described. Survival rates in this cohort equal or exceed contemporary figures observed in Eastern Cooperative Oncology Group advanced NSCLC trials.     

晚期胰腺癌患者应用GS方案一线化疗引起的中性粒细胞减少与预后的相关性

目的:探讨晚期胰腺癌患者应用吉西他滨联合替吉奥方案一线化疗引起的中性粒细胞减少(chemotherapy induced neutropenia,CIN)与预后的相关性。方法:回顾性分析2012年7月至2016年6月,接受吉西他滨联合替吉奥方案一线化疗的37例晚期胰腺癌患者,根据CTCAE(common terminology criteria for adverse events) 4.0的标准,将中性粒细胞减少分级为G0级,G1级,G2级,G3级,G4级。观察患者化疗2周期内出现的中性粒细胞减少程度,利用Kaplan-Meier曲线和COX风险模型分析CIN与总生存时间（OS）的相关性。结果:晚期胰腺癌患者接受吉西他滨联合替吉奥方案一线化疗后,未发生CIN（0级）的患者中位总生存期为158天（95%CI:128~187天）,发生CIN（1-4级）患者中位总生存期294天（95%CI,211~368天）。多因素分析显示,发生CIN（HR:0.379,95%CI:0.177~0.811,P=0.012）和接受二线化疗（HR:0.426,95%CI:0.186~0.976,P=0.044）是晚期胰腺癌患者接受吉西他滨联合替吉奥方案一线化疗的独立预后因素。结论:CIN是晚期胰腺癌一线GS方案化疗判断预后的独立影响因素,监测CIN将有助于早期判断预后并及时调整化疗药物剂量。     

A New Inflammatory Prognostic Index,Based on C-reactive Protein,the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein × NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.     

Efficacy of First-line Chemotherapy Affects the Second-Line Setting Response in Patients with Advanced Non-Small Cell Lung Cancer

Background: Chemotherapy is the mainstay of treatment for the majority of patients with advanced nonsmall cell lung cancer (NSCLC) without driver mutations and many receive therapies beyond first-line. Secondline chemotherapy has been disappointing both in terms of response rate and survival and we know relatively little about the prognostic factors. Materials and Methods: One thousand and eight patients with advanced NSCLC who received second-line chemotherapy after progression were reviewed in Shanghai PulmonaryHospital, China, from September 2005 to July 2010. We analyzed the effects of potential prognostic factors on the outcomes of second-line chemotherapy (overall response rate, ORR; progression free survival, PFS; overall survival, OS). Results: The response and progression free survival of first-line chemotherapy affects the ORR, PFS and OS of second-line chemotherapy (ORR: CR/PR 15.4%, SD 10.1%, PD2.3%, p<0.001; PFS: CR/PR 3.80 months, SD 2.77 months, PD 2.03 months, p<0.001; OS: CR/PR 11.60 months, SD 10.33 months, PD 6.57 months, p=0.578, p<0.001, p<0.001, respectively). On multivariate analysis, better response to first-line therapy (CR/PR: HR=0.751, p=0.002; SD: HR=0.781, p=0.021) and progression within 3-6 months (HR=0.626, p<0.001), together with adenocarcinoma (HR=0.815, p=0.017), without liver metastasis (HR=0.541, p=0.001), never-smoker(HR=0.772, p=0.001), and ECOG PS 0-1 (HR=0.745, p=0.021) were predictors for good OS following secondline chemotherapy. Conclusions: Patients who responded to first-line chemotherapy had a better outcome after second-line therapy for advanced NSCLC, and the efficacy of first-line chemotherapy, period of progression, histology, liver metastasis, smoking status and ECOG PS were independent prognostic factors for OS.     

Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data.

PURPOSE: (1) Identify clinical factors that can be used to predict survival in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy regimens, and (2) build a clinical model to predict survival in this patient population. PATIENTS AND METHODS: Using data from two randomized, phase III Eastern Cooperative Oncology Group (ECOG) trials (E5592/E1594), we performed univariate and multivariate stepwise Cox regression analyses to identify survival prognostic factors. We used 75% of randomly sampled data to build a prediction model for survival, and the remaining 25% of data to validate the model. RESULTS: From 1993 to 1999, 1,436 patients with stage IV or IIIB NSCLC with effusion were treated with platinum-based doublets (involving either paclitaxel, docetaxel, or gemcitabine). The response rate and median survival time were 20% and 8.2 months, respectively. One- and 2-year survivals were 33% and 11%, respectively. In multivariate analysis, six independent poor prognostic factors were identified: skin metastasis (hazard ratio [HR], 1.88), lower performance status (ECOG 1 or 2; HR, 1.46), loss of appetite (HR, 1.62), liver metastasis (HR, 1.32), >/= four metastatic sites (HR, 1.20), and no prior surgery (HR, 1.16). A nomogram using six pretreatment prognostic factors was built to predict 1- and 2-year survival. CONCLUSION: Six pretreatment factors can be used to predict survival in chemotherapy-naive NSCLC patients treated with standard chemotherapy. Using our prognostic nomogram, 1- and 2-year survival probability of NSCLC patients can be estimated before treatment. This prognostic model may help clinicians and patients in clinical decision making, as well as investigators in research planning.     

Individualized Chemotherapy for Metastatic Gastric Cancer: Retrospective Data from a University Hospital in Brazil

Background: Despite the decreased incidence, gastric cancer is still a frequent cause of cancer related death.The 1st line 2 or 3 drugs regimen is still a debatable issue. HER2 targeted therapy has emerged as the standard ofcare, but it is unavailable in the Brazilian Public Health System. The end-point of this trial was overall survival(OS) in patients with metastatic gastric cancer treated in a public university hospital in Brazil. The secondaryend-points were efficacy and safety of regimens with 2 (F+P) or 3 (EOX) drugs to develop an institutionalguideline to facilitate optimal treatments. Materials and Methods: In this retrospective study, 1st line regimenswere evaluated for OS and PFS stratified by age and ECOG using Cox regression. Results: 47 patients weretreated over the last 3 years. In 1st line, 29 were treated with F+P (mean 59.3 years, 34.5% ECOG 2 and a meanof 5.69 cycles) and 16 with EOX (mean 47 years, 18.8% ECOG 2 and a mean of 5.44 cycles). The median OSwas 13.8 months (95%CI 10.7-16.9). Response was evaluated in 40 cases and was 64.3% for EOX and 37.5% forF+P (p=0.25). The median PFS was 9.5 months for EOX and 5.6 months for F+P (HR 0.85, 95%CI 0.41-1.74).However, among patients with ECOG 2 mPFS was 3.70 vs 5.40 months, respectively (p=0.86). Regimens showedsimilar manageable adverse events. A total of 34 patients suffered progression and 14 received 2nd line therapy.Diffuse histology (HR 1.89, 95%CI 1.22-2.88), achieving 2nd line (HR: 0.25, 95%CI 0.11-0.58) and treatmentresponse (HR 0.23, 95%CI 0.12-0.47) were OS prognostic factors. Conclusions: Patients treated in our hospitalhad outcomes compatible with the literature. The regimen choice should be related to patient features. Secondline treatment should be considered.     

螺旋断层放疗治疗转移性非小细胞肺癌的预后分析

目的 探讨转移性非小细胞肺癌（NSCLC）患者接受螺旋断层放疗后的预后情况及其影响因素。方法 对本院2011年6月至2013年2月采用螺旋断层放疗技术治疗的51例转移性NSCLC患者的临床资料进行回顾性分析。所有靶区的中位放疗剂量为42.5 Gy（30～62 Gy）,单次放疗的中位剂量2 Gy（1.8～3 Gy）。应用Kaplan-Meier法计算生存率,Log-rank检验比较组间的生存差异,Cox风险比例回归模型分析影响预后的各种因素。结果 所有患者随访时间均超过1年。51例转移性NSCLC患者的中位生存时间为19.3个月,1年生存率为64.7％。单因素分析显示,KPS评分高、病理类型为腺癌、放疗前接受过化疗、无肝转移和所有病灶计划靶区体积（PTV）≤1300 cm³是NSCLC患者预后良好的影响因素（P＜0.05）;Cox多因素分析显示KPS评分、放疗前是否化疗和所有病灶PTV是转移性NSCLC患者采用螺旋断层放疗的独立预后因素。结论 转移性NSCLC采用螺旋断层放疗对延长患者的生存时间及改善预后可能有重要意义。     

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.     

Is chemotherapy in elderly patients with metastatic or recurrent gastric cancer as tolerable and effective as in younger patients?

Aim: To analyze the chemotherapy regimens and outcomes of advanced gastric cancer (AGC) patients older than 70 years of age. Methods: Between May 2001 and October 2009, 1135 patients with metastatic or recurrent gastric cancer received palliative chemotherapy. Of these patients 56 (4.9%) were ≥70 years old and were analyzed retrospectively. Results: The median age at the time of first‐line chemotherapy was 73 years (range, 70–85) and the median Charlson comorbidity index was 0 (0–5). In all 17 patients (30%) received surgery with curative or palliative intent; 43 (77%) were treated by doublet or triplet first‐line chemotherapy regimens and 13 patients (23%) received single agent chemotherapy. Median progression‐free survival for first‐line chemotherapy was 3.97 months (95% CI 2.05–5.89) with an overall response rate of 26%. After the first‐line chemotherapy, only 18 of 56 (32%) patients received second‐line chemotherapy. The median overall survival (OS) was 12.4 months (95% CI 2.81–21.99). In multivariate analysis, receiving surgery and disease control for first‐line chemotherapy were independent prognostic factors for increased OS for all 56 patients. Conclusion: Patients older ≥70 years with metastatic or recurrent gastric cancer might achieve clinical benefit from chemotherapy. Receiving surgery and response of over more stable disease for first‐line chemotherapy were independent prognostic factors for increased OS.     

Fatty Acid Synthesis Pathway Genetic Variants and Clinical Outcome of Non-Small Cell Lung Cancer Patients after Surgery

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Coxproportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Ourdata suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.