Prognostic Role of Circulating Tumor Cells in Patients with Pancreatic Cancer: a Meta-analysis

Background: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. Materials and Methods: Initial literature was identified using Medlineand EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). Results: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00-1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post-treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). Conclusions: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment.     

MTHFR C677T Polymorphism and Pancreatic Cancer Risk:a Meta-analysis

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate,and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Method: Aliterature search was performed using Pubmed and CNKI databases for published studies through May 2012.We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFRC677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a totalof 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysisshowed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancerrisk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41).However, no significant association was found in Caucasians. Conclusion: The MTHFR C677T polymorphismis associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studieswith a larger sample size are needed to further clarify this association.     

PD-1和PD-L1与胃癌患者预后相关性的Meta分析CSCD

目的系统评价PD-1和PD-L1的表达对胃癌患者预后的影响。方法对PubMed、Web of Science、Cochrane Library、中国生物医学数据库(CBM)、Embase、中国知网(CNKI)等数据库进行文献检索。纳入研究为PD-1/PD-L1表达与胃癌患者预后关系的队列研究。采用RevMan 5.3软件对总生存期(OS)进行Meta分析。结果共纳入10项(3 093例胃癌患者)符合条件的队列研究。单因素和多因素分析显示,PD-1和PD-L1的表达与胃癌患者预后无明显相关性,PD-1的高表达与淋巴结转移(N^+)有显著相关性,PD-L1的高表达与胃癌晚期(Ⅲ~Ⅳ)有显著相关性。结论 PD-1和PD-L1表达与胃癌患者预后无明显相关性。     

Prognostic Factors of Survival in a Randomized Phase III Trial (MPACT) of Weekly nab‐Paclitaxel Plus Gemcitabine Versus Gemcitabine Alone in Patients With Metastatic Pancreatic Cancer

Background.

nab-Paclitaxel in combination with gemcitabine has emerged as a new treatment option for patients with metastatic pancreatic cancer (MPC), based on superiority over gemcitabine demonstrated in the phase III MPACT trial. Previously, Karnofsky performance status (KPS) score and the presence of liver metastases were shown to be predictive of survival with nab-paclitaxel plus gemcitabine treatment. This analysis sought to further explore the relationship between clinical characteristics and survival in the MPACT trial and to identify potential predictors of overall survival and progression-free survival in patients with MPC.

Materials and Methods.

Cox regression models adjusted for stratification factors and a stepwise multivariate analysis of prespecified baseline prognostic factors were performed.

Results.

Treatment effect was significantly associated with survival, with a similar magnitude of reduction in risk of death compared with the previously reported primary analysis. Treatment effect consistently favored nab-paclitaxel plus gemcitabine across the majority of the prespecified factors. In addition to KPS score and presence of liver metastases, age and number of metastatic sites were independent prognostic factors of overall and progression-free survival. Baseline carbohydrate antigen 19-9 was not found to be an independent prognostic factor of survival in this analysis.

Conclusion.

The results of this analysis confirm broad utility of nab-paclitaxel plus gemcitabine for the treatment of MPC. In addition, these findings suggest that KPS score, presence of liver metastases, age, and number of metastatic sites are important predictors of survival that may be useful when making treatment decisions and designing future clinical trials.     

吉西他滨联合顺铂或氟尿嘧啶治疗晚期胰腺癌临床疗效的比较

目的　比较GP方案 (吉西他滨 顺铂 )与GF方案 (吉西他滨 氟尿嘧啶 )治疗晚期胰腺癌的近期疗效和毒副作用。方法　经病理组织学或细胞学检查证实的 60例胰腺癌患者 ,随机分为GP组和GF组 ,各 3 0例。GP组给予吉西他滨 10 0 0mg/m2加生理盐水 10 0ml,静脉滴注 3 0min ,第 1、8、15天 ;顺铂 40mg ,静脉滴注 ,第 15、16、17天。GF组给予吉西他滨 10 0 0mg/m2 加生理盐水 10 0ml ,静脉点滴 3 0min ,第 1、8、15天 ;氟尿嘧啶 5 0 0mg/m2 加 5 %GS 5 0 0ml ,静脉滴注时间超过 6h ,第 1～ 5天。结果　GP组PR 3例 ,MR 5例 ,NC 12例 ,PD 5例 ,PR MR为 3 2 .0 % ,中位生存期为 8.7个月 ,临床受益反应率 (CBR )为 5 7.7% (15 /2 6) ,CA 19 9水平下降超过 5 0 %者达 48.1% (13 /2 7)。GF组PR 3例 ,MR 8例 ,NC 9例 ,PD 4例 ,PR MR为 45 .8% ,中位生存期为 10 .1个月 ,CBR 82 .1% (2 3 /2 8) ,CA19 9水平下降超过 5 0 %者达 5 3 .6% (15 /2 8)。 2组比较 ,CBR有显著性差异 (P <0 .0 5 ) ,GF疗效较佳。不良反应主要为白细胞减少和血小板减少 ,2组无显著性差异。结论　含吉西他滨的联合化疗方案与以往单药方案比较 ,疗效高、副作用小、患者中位生存期长 ,临床受益反应率 (CBR )高 ;GP方案和GF方案比较 ,后者CBR更高 (5     

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.     

GP方案与LFEM方案治疗晚期胰腺癌疗效的比较

目的比较GP(健择-DDP)与LFEM(CF、5-Fu、MMC、EPI)方案治疗晚期胰腺癌的近期疗效与不良反应.方法将40例晚期胰腺癌患者随机分为治疗组和对照治疗组,分别采用GP与LFEM方案化疗2个周期,按WHO标准评定疗效和不良反应.结果2组有效率(CR+PR)分别为35%和15%,治疗组高于对照组(P＞0.05),2组不良反应比较无显著性差异.不良压应主要为骨髓抑制和胃肠道反应.结论健择联合顺铂是治疗晚期胰腺癌的1种安全有效的化疗方案.     

MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to beassociated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessedthe relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysisapproach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized.The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was alsocalculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included inthis meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25;Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CCvs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01,95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk.Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associatedwith pancreatic cancer risk.     

Gemcitabine and S-1 combination chemotherapy versus gemcitabine alone for locally advanced and metastatic pancreatic cancer: a meta-analysis of randomized controlled trials in Asia

Abstract

Introduction:

After decades of research, pancreatic cancer is still a devastating disease. The aim of this article was to assess the efficacy and safety of combination chemotherapy with gemcitabine (GEM) and S-1 (GS) therapy compared with GEM alone therapy in patients with locally advanced or metastatic pancreatic cancer.     

亚甲基四氢叶酸还原酶基因多态性与中国人群食管癌易感性的Meta分析

目的运用Meta分析的方法综合评价中国人群中亚甲基四氢叶酸还原酶（MTHFR）基因多态性与食管癌发病的相关性。方法通过计算机文献检索中国生物医学文献数据库(CBM) 和PubMed数据库,并结合文献追溯、网上查询(www.baidu.com; www.google.cn)的方法,收集所有关于MTHFR基因多态性与食管癌易感性的病例对照研究或队列研究。以食管癌组与对照组人群基因型分布的OR值为效应指标,各资料间进行一致性检验,以确定采用固定或随机效应模型进行合并分析。发表偏倚用漏斗图和Egger’s线性回归检验来评估。结果共有在国内外发表的相关文献10篇纳入分析,Meta分析结果表明：MTHFR C677T基因多态和MTHFR A1298C基因多态合并OR值及其95%CI分别为1.97（1.69,2.30）,0.84(0.66,1.08)。按是否吸烟进行分层发现吸烟组中MTHFR 677CT/TT基因型与食管癌有关(OR=2.57,95%CI:1.73~3.80),而不吸烟组中未见MTHFR 677CT/TT基因型与食管癌存在关联（OR=1.33,95%CI:0.94~1.88)。结论中国人群MTHFR C677T基因多态性与食管癌易感性有关,MTHFR A1298C基因多态性与食管癌易感性无统计学关联。吸烟可能会增加MTHFR C677T基因型个体患食管癌的危险性。     

Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers.However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed toevaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients.Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer andChinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed todetermine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were includedin our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associatedwith poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overallsurvival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was noevidence of publication bias as suggested by Egger’s tests for tumor distant metastasis (p=1.000), differentiation(p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expressioniss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as anefficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.     

核苷酸还原酶亚单位M1和内切修复交叉补体1在非小细胞肺癌中的研究进展

核苷酸还原酶亚单位M1（RRM1）属抑癌基因，RRM1可以激发G2期检测点功能，使受损的DNA得以修复或者发生凋亡，并具有抑制细胞侵袭和转移的作用，另外RRM1还可以调节核苷酸还原酶的活性，是抗代谢药吉西他滨作用的靶分子，RRM1高表达的细胞对吉西他滨耐药。内切修复交叉补体1（ERCC1）是细胞内负责修复受损DNA的核苷酸内切修复通路中的限速酶，可以识别和去除铂-DNA附加物而导致细胞对铂类耐药。本文综述RRM1和ERCC1在非小细胞肺癌患者预后和化疗个体化方面的研究进展。     

ERCC1 in Advanced Biliary Tract Cancer Patients Treated with Chemotherapy: Prognostic and Predictive Roles

Background

In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown.

Methods

We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival.

Results

From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95 % CI 3.4 to 20.7; p?<?0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95 % CI 1.6 to 55.3; p?=?0.012). Pathology slides were available from 44 patients: 23 (52 %) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy.

Conclusions

In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival     

Risk of Serious Neutropenic Events in Cancer Patients Treated with Bevacizumab: A Meta-analysis

Bevacizumab has been approved for use in combination with chemotherapy to treat many types of cancerbut associated neutropenic events, including febrile neutropenia, have been reported. To estimate the incidenceand relative risk of neutropenic events in cancer patients treated with bevacizumab combination therapy, wesearched PubMed, EMBASE, and Web of Science literature databases, as well as abstracts presented at theAmerican Society of Clinical Oncology conferences, to identify relevant studies published from January 1966 toDecember 2011. Studies that compared bevacizumab plus chemotherapy or biological therapy with chemotherapyor biological therapy alone, and that had adequate safety data profiles, were selected for analysis. Statisticalanalyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidenceintervals (CIs) using fixed- or random-effects models. A total of 22 clinical trials involving 15,056 patients wereincluded in the analysis. The summary incidences of high-grade neutropenia (HGN) and high-grade febrileneutropenia (HGFN) in patients receiving bevacizumab was 27.3% (95% CI: 26.4%-28.3%) and 3.91% (95%CI: 3.51%-4.37%), respectively. The risks of HGN (RR=1.10; 95% CI: 1.02-1.19; P=0.02) and HGFN (RR=1.31;95% CI: 1.08–1.59; P=0.005) were significantly increased in bevacizumab-treated patients, compared to those whodid not receive bevacizumab. The RR of bevacizumab-associated HGN, but not HGFN, varied significantly withtumor types (P=0.005). The increased risk of bevacizumab-associated neutropenic events was dose-dependent,as the RR was greater at a dose of 5 mg/kg/week than at 2.5 mg/kg/week. Our findings suggest that bevacizumabaddition to cancer therapy significantly increases the risk of serious neutropenic events, and this risk may bedose-dependent.     

Chronic Hepatitis B Virus Infection and Risk of Pancreatic Cancer: A Meta-analysis

Objectives: A number of studies have shown that chronic hepatitis B virus infection is implicated insusceptibility to pancreatic cancer. However, the results are still controversial. This meta-analysis aimed toquantitatively assess the relationship between chronic hepatitis B virus infection and incidence of pancreaticcancer of cohort and case-control studies. Methods: A literature search was performed for entries from 1990 to2012 using PUBMED and EMBASE. Studies were included if they reported odds ratios (ORs) and corresponding95% CIs of pancreatic cancer with respect to the infection of hepatitis B virus. Results: Eight studies met theinclusion criteria, which included five case-control studies and three cohort studies. Compared with individualswho have not infection of hepatitis B virus, the pooled OR of pancreatic cancer was 1.403 (95%CI: 1.139-1.729,P=0.001) for patients with hepatitis B virus infection. Sub-group analysis by study design showed that thesummary OR was 1.43 (95%CI: 1.06-1.94, P=0.021) when pooling case-control studies and 1.31 (95%CI: 1.00-1.72, P=0.05) when pooling cohort studies. Conclusion: Findings from this meta-analysis suggest that chronichepatitis B virus infection may increase the risk of pancreatic cancer. This relationship needs to be confirmedby further follow-up studies.     

Methionine Synthase Reductase A66G Polymorphism is not Associated with Breast Cancer Susceptibility - a Meta-analysis

Background: Several studies have investigated the association between methionine synthase reductase(MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. Therefore, weperformed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibilityto breast cancer. Materials and Methods:Case-control studies investigating the relationship between MTRRA66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China NationalKnowledge Infrastructure and Wanfang Database. Either fixed-effects or random-effects models were appliedto calculate odds ratios(ORs) and 95% confidence intervals (CIs) by RevMan5.2 software. Results: A total of9 studies bearing 7,097 cases and 7,710 controls were included in the meta-analysis. The results were that thecombined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16)and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. We also performed subgroup analysis by specificethnicity. The results of the combined analysis of MTRR 66AG, GG, (AG+GG) genotypes and breast cancer inAsian descent were Z=0.50, 0.53 and 0.21, with p all>0.05; for breast cancer in Caucasian descent, the results wereZ=1.14, 1.65 and 0.43, with p all>0.05. Conclusions: Our findings suggested that MTRR A66G polymorphismwas not associated with breast cancer susceptibility.     

Genetic Polymorphisms of Glutathione S-transferase M1 and Prostate Cancer Risk in Asians: A Meta-analysis of 18 Studies

Background: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1)null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries isstill unclear owing to inconsistencies across results. Methods: We searched the PubMed, Web of Science, Scopus,Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostatecancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidenceintervals (95% CIs). Results: A total of 18 case-control studies with 2,172 cases and 3,258 controls were includedin this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased riskof prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001).Similar results were found in East Asians (OR=1.41; 95% CI: 1.12–1.78; P=0.004) and Caucasians in Asia(OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. Conclusions: This metaanalysisof available data suggested that the GSTM1 null genotype does contribute to increased risk of prostatecancer in people who live in Asian countries.