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。      

Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer

Since the prognosis of small cell lung cancer (SCLC) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination (PPV), in which vaccine antigens are selected based on pre-existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo- and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher antigen-specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi-weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide-specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD3(+) CD26(+) cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [HR] = 2.540, 95% confidence interval [CI] = 1.188-5.431, P = 0.016; HR = 0.941, 95% CI = 0.878-1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger-scale, prospective clinical trials.     

MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy

Objective: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. Methods: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. Results: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio(HR)= 2.01, 95% confidence intervals(CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P=0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. Conclusion: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.     

Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

BackgroundWe investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC).MethodsWe included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS.ResultsGlobal health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively).ConclusionThis study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.     

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

Sarcopenia is an independent unfavorable prognostic factor of non-small cell lung cancer after surgical resection: A comprehensive systematic review and meta-analysis

BackgroundWhether sarcopenia has any impact on long-term survival of patients with surgically treated non-small cell lung cancer (NSCLC) remains unclear. We conducted a meta-analysis focusing on current topic comprehensively for the first time.MethodsWe systematically searched relevant studies in PubMed, Embase, and Cochrane Library up to July 3, 2018. Data of 5-year overall survival (OS) and disease-free survival (DFS) rates as well as hazard ratio (HR) of OS were collected for analysis by using the STATA 12.0 package.ResultsA total of 6 cohort studies consisting of 1213 patients (422 patients with sarcopenia and 791 patients without) were included for analysis. Meta-analysis showed that patients with sarcopenia had a significantly lower 5-year OS rate (risk ratio (RR) = 1.63; 95% confidence interval (CI) = [1.13, 2.33]; P = 0.008) than those without, which was more prominent in patients with early-stage NSCLC. Sarcopenia was found to be an independent predictor of poor OS in patients with surgically treated NSCLC (HR = 2.85; 95%CI = [1.67, 4.86]; P < 0.001). With a limited sample size, there was no sufficient evidence of significantly different 5-year DFS rate between the two groups (RR = 1.14; 95%CI = [0.59, 2.17]; P = 0.70). However, in the subgroup of patients with early-stage NSCLC, sarcopenia was associated with a significantly lower 5-year DFS rate (RR = 1.59; 95%CI = [1.01, 2.52]; P = 0.046).ConclusionPatients with sarcopenia had a significantly worse prognosis than those without after surgical resection of NSCLC especially in those at early stage. Sarcopenia is an independent unfavorable prognostic factor for patients with surgically treated NSCLC. (246 words).     

The prognostic value of RASSF1A promoter hypermethylation in non-small cell lung carcinoma: a systematic review and meta-analysis

Inactivation of the tumor suppressor gene RASSF1A through methylation of the CpG islands within its promoter region as a prognostic factor for survival in non-small cell lung carcinoma (NSCLC) remains controversial. A meta-analysis of published studies investigating the effects of RASSF1A methylation on both relapse-free survival (RFS) and overall survival (OS) among NSCLC patients was performed. A total of 2802 patients from 19 eligible studies were included in the systematic review and 17 studies were included in the meta-analysis. In all, 32.6% of NSCLC patients had the methylated RASSF1A allele. Four of these studies investigated the correlation between RASSF1A methylation and RFS using univariate analysis. The univariate estimate for RFS was 1.87 [95% confidence interval (CI): 1.41-2.49; P < 0.0001] with no evidence of significant heterogeneity. Thirteen studies undertook univariate analyses of RASSF1A methylation and OS and 12 undertook multivariate analyses of RASSF1A methylation and OS. The pooled hazard ratio (HR) estimate for OS was 1.52 (95% CI: 1.33-1.74; P < 0.0001) by univariate analysis and 1.34 (95% CI: 1.15-1.57; P < 0.0001) by multivariate analysis. No significant heterogeneity was detected. For stages I-II NSCLC, the meta-risk remained highly significant by both univariate (HR = 1.94; 95% CI: 1.54-2.44; P < 0.0001) and multivariate analysis (HR = 1.39; 95% CI: 1.02-1.90; P = 0.039). This study shows that RASSF1A methylation appears to be an independent prognostic factor for poor survival in surgically treated NSCLC. However, the present findings require confirmation though adequately designed prospective studies.     

Lymph node ratio is a prognostic factor for non-small cell lung cancer

The lymph node ratio (LNR) is defined as the number of pathologically positive LNs divided by the number of LNs examined. Some studies reported that high LNR was significantly associated with poor survival of non-small cell lung cancer (NSCLC). However, other studies could not confirm this result. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies published up to July 2015. Primary outcome was the relationship between LNR and disease-specific survival (DSS) and overall survival (OS). Twelve studies with 25138 NSCLC patients were included in this meta-analysis. Higher LNR was significantly associated with decreased OS (HR = 1.93; 95% CI 1.64 – 2.28; P < 0.00001) and DSS (HR = 1.82; 95% CI 1.55 – 2.14; P < 0.00001). In the subgroup analysis, N1 stage NSCLC patients with higher LNR also showed decreased OS (HR = 1.60; 95% CI 1.25 – 2.28; P = 0.0002) and DSS (HR = 1.82; 95% CI 1.55 – 2.21; P < 0.0001). This meta-analysis indicated that LNR was an independent predictor of survival in patients with NSCLC.     

术前纤维蛋白原联合淋巴细胞与单核细胞比值对非小细胞肺癌患者预后的评估价值

  目的  探讨术前纤维蛋白原（fibrinogen,Fbg）联合淋巴细胞与单核细胞比值（lymphocyte to monocyte ratio,LMR）评分（FLMR）与非小细胞肺癌（non-small cell lung cancer,NSCLC）患者预后的相关性。  方法  回顾性分析2006年1月至2009年12月天津医科大学肿瘤医院行根治性手术切除的589例NSCLC患者的临床病例资料。根据受试者工作特征（ROC）曲线判定Fbg及LMR的界限值,根据F-LMR评分原则将患者分为3组:F-LMR 0分、F-LMR 1分、F-LMR 2分。通过χ2检验分析其与患者临床病理因素的关系,Kaplan-Meier法进行生存分析,运用Log-rank法进行差异性检验,Cox比例风险模型进行单因素与多因素回归分析。  结果  根据ROC曲线,3.48 g/L、3.23分别作为Fbg和LMR的界值。F-LMR 0分215例、F-LMR 1分228例、F-LMR 2分146例,术前F-LMR评分与年龄、性别、吸烟史、肿瘤位置、手术类型、病理分期、病理类型、肿瘤大小有显著相关（P < 0.05）。单因素分析显示:肿瘤位置、手术类型、病理分期、肿瘤大小、F-LMR评分、LMR及Fbg水平是影响NSCLC患者预后的危险因素（P < 0.05）;多因素分析结果表明:病理分期（DFS:HR:1.700,95%CI:1.483~1.950,P < 0.001;OS:HR:1.703,95%CI:1.486~1.952,P < 0.001）和F-LMR评分（DFS:HR:1.264,95%CI:1.077~1.484,P=0.004;OS:HR:1.301,95%CI:1.107~1.528,P=0.001）是影响患者预后的独立危险因子。  结论  术前F-LMR评分可作为预测行根治性切除的非小细胞肺癌患者预后的指标。      

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis

Objectives: Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. Materials and Methods: We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. Results: From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 – 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 – 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 – 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 – 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 – 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 – 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 – 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 – 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 – 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 – 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. Conclusion: Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.     

非小细胞肺癌组织PD-L1表达的预后意义及其与SUVmax的相关性

  目的  本研究前期探索了程序性死亡配体1（programmed death-ligand 1,PD-L1）在非小细胞肺癌（non-small cell lung carcinoma,NSCLC）组织表达及其与临床因素的关系,发现它与肿瘤分期存在正相关性,进一步分组研究其预后意义及与原发灶最大标准摄取值（maximum standardized uptake value,SUVmax）相关性。  方法  收集2008年4月至2014年8月122例就诊于天津医科大学肿瘤医院初治原发NSCLC患者的临床影像病理及随访资料,免疫组织化学法检测PD-L1表达情况,采用Kaplan-Meier法及Cox模型进行PD-L1表达的预后分析,Spearman检验分析PD-L1表达与SUVmax的相关性。  结果  早期NSCLC患者中,PD-L1（HR=4.518,95%CI:1.176-17.352,P=0.028）和肿瘤最大径（HR=1.404,95%CI:1.020-1.933,P=0.037）影响总生存时间（overall survival,OS）,是OS的独立预后因子,性别、年龄、病理类型、CEA水平和SUVmax分组对OS差异无统计学意义（P>0.05）;Ⅲ~Ⅳ期NSCLC患者中,性别、病理类型、肿瘤最大径和SUVmax分组是OS的影响因素,年龄、CEA水平、PD-L1表达水平不是OS的影响因素。本研究中,PD-L1表达与SUVmax水平无相关性。  结论  PD-L1表达是早期NSCLC患者独立预后因子,尚不能成为分期较晚患者的预后因素。PD-L1表达与原发灶SUVmax无相关性。      

Is the positive predictive value of high-grade cytology in predicting high-grade cervical disease falling due to HPV vaccination?

A fall in the positive predictive value (PPV) of cytological predictions of high-grade squamous intra-epithelial lesions (HSIL) or adenocarcinoma-in-situ (AIS) has been predicted in the post-HPV vaccination era due to the decrease in underlying prevalence of cervical lesions. Data was extracted from the Victorian Cervical Screening Registry including cervical cytology tests taken between 2000 and 2016 and any subsequent histology performed within 6 months of the cytology. PPV was calculated for each age group (<20, 20–24, 25–29, 30–34, 35–39, 40–49, 50–59, 60–69, 70+ years) and calendar year. The x2 (chi-square) test was used to identify significant trends in PPV over time in each age group in both the pre-vaccination (2000–2006) and the post-vaccination (2007–2016) periods. The overall PPV of HSIL/AIS cytology in predicting histologically confirmed high grade disease (HGD, HSIL/AIS+) was 75% and this was consistent across the different calendar years. When stratified by age group, there was a decreasing trend in the PPV in women aged <20 years (p_trend = 0.0006) and 20–24 years (p_trend = 0.0004) in the post-vaccination period but not in the pre-vaccination period (p_trend = 0.82 and p_trend = 0.73, respectively). No such decline in PPV was noted in either the pre-vaccination or the post-vaccination periods for any other age groups except the oldest women, aged 60–69 years and 70+ years. The decline in PPV of HSIL/AIS cytology in predicting HGD in age groups <20 and 20–24 years in the post-vaccination period could be an impact of the HPV vaccination.     

Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised clinical trial

Background:The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies.Methods:From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS).Results:The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively).Conclusion:SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.     

Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non‐small‐cell lung cancer

This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non‐small‐cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty‐eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease‐free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P_trend < 0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS = 3.53, 95% confidence interval [CI] = 1.25–9.97, P = 0.02, and aHR for DFS = 3.31, 95% CI = 1.41–7.76, P = 0.006; and aHR for OS = 5.47, 95% CI = 1.87–16.00, P = 0.002, and aHR for DFS = 4.42, 95% CI = 1.82–10.74, P = 0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC. (Cancer Sci 2010; 101: 2436–2442)     

A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer

Imetelstat, a novel telomerase inhibitor, failed to improve significantly median PFS and OS as maintenance therapy (±bevacizumab) in advanced NSCLC. Telomere length (TL) biomarker results were consistent with the hypothesis that telomerase inhibition is of greater benefit to patients with tumors possessing shorter telomeres; the patients with shorter TL had a trend toward longer median PFS and OS.BackgroundContinuation or ‘switch’ maintenance therapy is commonly used in patients with advancd non-small-cell lung cancer (NSCLC). Here, we evaluated the efficacy of the telomerase inhibitor, imetelstat, as switch maintenance therapy in patients with advanced NSCLC.Patients and methodsThe primary end point of this open-label, randomized phase II study was progression-free survival (PFS). Patients with non-progressive, advanced NSCLC after platinum-based doublet (first-line) chemotherapy (with or without bevacizumab), any histology, with Eastern Cooperative Oncology Group performance status 0–1 were eligible. Randomization was 2 : 1 in favor of imetelstat, administered at 9.4 mg/kg on days 1 and 8 of a 21-day cycle, or observation. Telomere length (TL) biomarker exploratory analysis was carried out in tumor tissue by quantitative PCR (qPCR) and telomerase fluorescence in situ hybridization.ResultsOf 116 patients enrolled, 114 were evaluable. Grade 3/4 neutropenia and thrombocytopenia were more frequent with imetelstat. Median PFS was 2.8 and 2.6 months for imetelstat-treated versus control [hazard ratio (HR) = 0.844; 95% CI 0.54–1.31; P = 0.446]. Median survival time favored imetelstat (14.3 versus 11.5 months), although not significantly (HR = 0.68; 95% CI 0.41–1.12; P = 0.129). Exploratory analysis demonstrated a trend toward longer median PFS (HR = 0.43; 95% CI 0.14–1.3; P = 0.124) and overall survival (OS; HR = 0.41; 95% CI 0.11–1.46; P = 0.155) in imetelstat-treated patients with short TL, but no improvement in median PFS and OS in patients with long TL (HR = 0.86; 95% CI 0.39–1.88; and HR = 0.51; 95% CI 0.2–1.28; P = 0.145).ConclusionsMaintenance imetelstat failed to improve PFS in advanced NSCLC patients responding to first-line therapy. There was a trend toward a improvement in median PFS and OS in patients with short TL. Short TL as a predictive biomarker will require further investigation for the clinical development of imetelstat.     

Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).

BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.     

细胞因子诱导的杀伤细胞治疗87例非小细胞肺癌临床疗效评价

  目的   评价细胞因子诱导的杀伤细胞（cytokine-induced killer cells,CIK）联合化疗治疗非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效。   方法   收集天津医科大学附属肿瘤医院2003年1月至2008年3月接受CIK细胞联合化疗治疗的87例NSCLC患者作为联合治疗组,接受单纯化疗的87例NSCLC患者作为对照组。Ⅰ~ⅢA期为早期,Ⅳ期为晚期。配对因素包括性别、年龄、吸烟情况、病理类型、KPS评分、临床分期、是否手术、乳酸脱氢酶（lactate dehydrogenase,LDH）、血小板、血红蛋白、治疗情况等。观察终点为无进展生存期（progression-free survival,PFS）和总生存期（overall survival,OS）。对于未取得中位OS或PFS组用平均OS或PFS表示。   结果   联合治疗组与单纯化疗组2年PFS率分别为47%、36%（P < 0.05）,2年OS率分别为71%、43%（P < 0.001）。两组患者中位PFS分别为24、12个月（P < 0.05）,中位OS分别为48、18个月（P=0.001）。早期患者中联合治疗组与单纯化疗组2年PFS率、中位PFS差异无明显统计学意义（74% vs. 58%,P=0.138;57个月vs. 45个月,P=0.093）,联合治疗组2年OS率及中位OS明显高于单纯化疗组（92% vs. 72%,P < 0.05;73个月vs. 53个月,P < 0.05）。晚期患者中联合治疗组与单纯化疗组2年PFS率分别为13%、5%（P < 0.001）,2年OS率分别为42%、3%（P < 0.001）,两组患者中位PFS分别为13、6个月（P=0.001）,中位OS分别为24、10个月（P=0.001）。多因素分析显示临床分期及CIK治疗周期数是联合治疗组肺癌患者的独立预后因素。   结论   CIK细胞联合化疗能够延长肺癌患者的总体生存时间,并延长晚期患者的无进展生存时间,显著改善肺癌患者预后。CIK细胞治疗多于7个周期者疗效更好。      

The prognostic value of sarcopenia in patients with surgically treated urothelial carcinoma: A systematic review and meta-analysis

ObjectiveSarcopenia is associated with unfavorable prognosis in patients undergoing surgical treatments of the respiratory tract, gastrointestinal tract and urinary tracts. We summarized all available evidence to investigate the prognostic value of sarcopenia in patients with surgically treated urothelial carcinoma (UC).MethodsWe conducted a comprehensive study search up to January 2019, searching the online database Embase, PubMed and Cochrane Library. The hazard ratio (HR) and 95% confidence interval (CI) were extracted from the studies.ResultsA total of 12 research consisting of 2075 patients were enrolled in the quantitative synthesis. We observed that UC patients with sarcopenia had a worse OS (HR = 1.87; 95%CI 1.43–2.45; P < 0.001) and CSS (HR = 1.98; 95%CI 1.43–2.75; P < 0.001). Stratified by tumor, sarcopenia is also an unfavorable factor for OS and CSS in patients with upper tract urothelial carcinoma (UTUC) or urothelial carcinoma of bladder (UCB).ConclusionSarcopenia is an unfavorable factor for OS and CSS in patients with surgically treated UC. Besides, stratified by tumor, the results of patients with UTUC or UCB are consistent with previous results. More prospective studies are required to validate our findings.