Chemotherapy Plus Best Supportive Care versus Best Supportive Care in Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Background

The use of chemotherapy has been proposed to increase the effectiveness of best supportive care (BSC) in patients with non-small cell lung cancer (NSCLC). Previous trials reported inconsistent findings regarding the efficacy and safety of chemotherapy on overall survival (OS) and treatment-related mortality. We performed a systematic review and meta-analysis to evaluate the effects of chemotherapy plus BSC versus BSC alone on survival of patients with NSCLC.

Methodology and Principal Findings

We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literature. All eligible studies included patients with NSCLC who had received chemotherapy and BSC or BSC alone. All eligible studies measured at least 1 of the following outcomes: OS or treatment-related mortality. Overall, patients that received chemotherapy plus BSC had significant longer OS than those that received BSC alone (HR, 0.76; 95%CI, 0.69–0.84; P<0.001). Additionally, chemotherapy plus BSC as compared to BSC alone resulted in a 28% RR reduction (95%CI: 12–40; P = 0.001) in 6-month mortality, 11% RR reduction (95%CI: 8–15; P<0.001) in 12-month mortality, and 5% RR reduction (95%CI: 1–8; P = 0.02) in 2-year mortality. Toxicity was greater in patients that received chemotherapy plus BSC.

Conclusion/Significance

Chemotherapy plus BSC increased the OS and reduced the 6-month, 12-month, and 2-year mortality of NSCLC patients.     

Multi-Targeted Antiangiogenic Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer: Meta-Analyses of 20 Randomized Controlled Trials and Subgroup Analyses

Background

Multi-targeted antiangiogenic tyrosine kinase inhibitors (MATKIs) have been studied in many randomized controlled trials (RCTs) for treatment of advanced non-small cell lung cancer (NSCLC). We seek to summarize the most up-to-date evidences and perform a timely meta-analysis.

Methods

Electronic databases were searched for eligible studies. We defined the experimental arm as MATKI-containing group and the control arm as MATKI-free group. The extracted data on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) were pooled. Subgroup and sensitivity analyses were conducted.

Results

Twenty phase II/III RCTs that involved a total of 10834 participants were included. Overall, MATKI-containing group was associated with significant superior ORR (OR 1.29, 95% CI 1.08 to 1.55, P = 0.006) and prolonged PFS (HR 0.83, 0.78 to 0.90, P = 0.005) compared to the MATKI-free group. However, no significant improvements in DCR (OR 1.08, 1.00 to 1.17, P = 0.054) or OS (HR 0.97, 0.93 to 1.01, P = 0.106) were observed. Subgroup analyses showed that the benefits were predominantly presented in pooled results of studies enrolling previously-treated patients, studies not limiting to enroll non-squamous NSCLC, and studies using MATKIs in combination with the control regimens as experimental therapies.

Conclusions

This up-to-date meta-analysis showed that MATKIs did increase ORR and prolong PFS, with no significant improvement in DCR and OS. The advantages of MATKIs were most prominent in patients who received a MATKI in combination with standard treatments and in patients who had previously experienced chemotherapy. We suggest further discussion as to the inclusion criteria of future studies on MATKIs regarding histology.     

The Prognostic Value of SOX2 Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.

Methods

Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.

Results

A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).

Conclusions

SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.     

Efficacy and Safety Profile of Combining Vandetanib with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To evaluate the efficacy and safety profile of combining vandetanib with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched. Eligible studies were the randomized clinical trials (RCTs) that compared the efficacy and safety profile of adding vandetanib to chemotherapy with single chemotherapy in patients with advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1, or I²>50%), further analysis (subgroup analysis, sensitivity analysis or random-effect model) was performed to identify potential cause.

Results

Results reported from 5 RCTs involving 2284 patients were included in the analysis. Compared to chemotherapy alone, the addition of vandetanib resulted in a significant longer PFS (HR 0.79 [0.72–0.87], p<0.00001) and a higher ORR (RR 1.75 [1.43–2.15], p<0.00001), but failed to show advantage on OS (HR 0.96 [0.87–1.06], p = 0.44).

Conclusion

Vandetanib has activity in NSCLC. Identification of predictive biomarkers is warranted in future trials to select a subset of patients with advanced NSCLC who may benefit from vandetanib.     

术前血清CEA 水平与非小细胞肺癌预后关系的Meta 分析*

目的:采用Meta分析的方法评估术前血清CEA(carcinoembryonic antigen)高水平与非小细胞肺癌(NSCLC)预后之间的关系。方法:从PubMed、EMBASE数据库中查找血清CEA水平与NSCLC预后关系的相关研究,收集每篇文献的相对危险比(hazard ratio,HR)以及95%可信区间(95%C1),应用Meta分析Dersimonian-Laird模型对文献进行定量综合分析。结果:共入选13篇文献,累计研究CEA与NSCLC预后关系的病例3505例。对入选13篇文献进行一致性检验,文献具有异质性(Q=2201.96,P=0.000),合并相对危险比HR为2.33(95%可信区间:2.03-2.68,P=0.000)。结论:术前血清CEA高浓度水平可能是NSCLC的不良预后因素。     

The Prognostic Value of Phosphorylated AKT Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objectives

Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed.

Materials and Methods

A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model.

Results

A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis.

Conclusion

Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform.     

Thoracoscopic Lobectomy versus Open Lobectomy in Stage I Non-Small Cell Lung Cancer: A Meta-Analysis

The objective of the present meta-analysis was to evaluate the survival, recurrence rate, and complications in patients with stage I non-small cell lung cancer (NSCLC) who received video-assisted thoracoscopic surgery (VATS) or open lobectomy. A literature search was conducted on June 31, 2012 using combinations of the search terms video-assisted thoracic surgery, open thoracotomy, lobectomy, and non-small-cell lung cancer (NSCLC). Inclusion criteria were: 1) Compared video-assisted thoracic surgery (VATS) lobectomy with open lobectomy. 2) Stage I NSCLC. 2) No previous treatment for lung cancer. 4) Outcome data included 5-year survival rate, complication, and recurrence rate. Tests of heterogeneity, sensitivity, and publication bias were performed. A total of 23 studies (21 retrospective and 2 prospective) met the inclusion criteria. VATS was associated with a longer 5-year survival (odds ratio [OR] = 1.622, 95% confidence interval [CI] 1.272 to 2.069; P<0.001), higher local recurrence rate (OR = 2.152, 95% CI 1.349 to 3.434; P = 0.001), similar distant recurrence rate (OR = 0.91, 95% CI 0.33 to 2.48; P = 0.8560), and lower total complication rate (OR = 0.45, 95% CI 0.24 to 0.84; P = 0.013) compared to open lobectomy. VATS was also associated with lower rates arrhythmias, prolonged air leakage, and pneumonia but it did not show any statistical significance. Patients with stage I NSCLC undergoing VATS lobectomy had longer survival and fewer complications than those who received open lobectomy.     

Meta-Analysis of EGFR Tyrosine Kinase Inhibitors Compared with Chemotherapy as Second-Line Treatment in Pretreated Advanced Non-Small Cell Lung Cancer

Background

Since efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy in the treatment of patients with pretreated advanced non-small cell lung cancer (NSCLC) remain controversial, we performed a meta-analysis to compare them.

Methods

An internet search of several databases was performed, including PubMed, Embase, and the Cochrane database. Randomized trials that compared an EGFR-TKI with chemotherapy in the second-line setting were included. The outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3–4 toxicities. The PFS, OS for the EGFR mutation-positive (EGFR M⁺) and EGFR mutation-negative (EGFR M⁻) subgroups were pooled. The pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated on the STATA software.

Results

Our meta-analysis combined 3,825 patients from 10 randomized trials. Overall, EGFR-TKIs and second-line chemotherapy have equivalent efficacy in terms of PFS (HR, 1.03; 95%CI, 0.87–1.21; P = 0.73; I² = 78.7%, P_{heterogeneity}<0.001), OS (HR, 1.00; 95%CI, 0.92–1.08; P = 0.90; I² = 0.0%, P_{heterogeneity} = 0.88), and ORR (OR, 1.34; 95%CI, 0.86–2.08; P = 0.20; I² = 73.1%, P_{heterogeneity}<0.001). However, subgroup analysis based on EGFR mutation status showed that second-line chemotherapy significantly improved PFS (HR, 1.35; 95%CI, 1.09–1.66; P = 0.01; I² = 55.7%, P_{heterogeneity} = 0.046) for EGFR M⁻ patients, whereas OS was equal (HR, 0.96; 95%CI, 0.77–1.19; P = 0.69; I² = 0.0%, P_{heterogeneity} = 0.43); EGFR-TKIs significantly improved PFS (HR, 0.28; 95%CI, 0.15–0.53; P<0.001; I² = 4.1%, P_{heterogeneity} = 0.35) for EGFR M⁺ patients, whereas OS was equal (HR, 0.86; 95%CI, 0.44–1.68; P = 0.65; I² = 0.0%, P_{heterogeneity} = 0.77). Compared with chemotherapy, EGFR-TKIs led to more grade 3–4 rash, but less fatigue/asthenia disorder, leukopenia and thrombocytopenia.

Conclusions

Our analysis suggests that chemotherapy in the second-line setting can prolong PFS in EGFR M⁻ patients, whereas it has no impact on OS. EGFR-TKIs seem superior over chemotherapy as second-line therapy for EGFR M⁺ patients. Our findings support obtaining information on EGFR mutational status before initiation of second-line treatment.     

Prognostic Value of 18F-FDG PET/CT in Surgical Non-Small Cell Lung Cancer: A Meta-Analysis

Background

The identification of surgical non-small cell lung cancer (NSCLC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. This meta-analysis explored the prognostic value of maximal standardized uptake value (SUV_max), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients.

Materials and Methods

MEDLINE, EMBASE and Cochrane Libraries were systematically searched until August 1, 2015. Prospective or retrospective studies that evaluated the prognostic roles of preoperative 18F-FDG PET/CT with complete DFS and OS data in surgical NSCLC patients were included. The impact of SUV_max, MTV or TLG on survival was measured using hazard ratios (HR). Sub-group analyses were performed based on disease stage, pathological classification, surgery only and cut-off values.

Results

Thirty-six studies comprised of 5807 patients were included. The combined HRs for DFS were 2.74 (95%CI 2.33–3.24, unadjusted) and 2.43 (95%CI: 1.76–3.36, adjusted) for SUV_max, 2.27 (95%CI 1.77–2.90, unadjusted) and 2.49 (95%CI 1.23–5.04, adjusted) for MTV, and 2.46 (95%CI 1.91–3.17, unadjusted) and 2.97 (95%CI 1.68–5.28, adjusted) for TLG. The pooled HRs for OS were 2.54 (95%CI 1.86–3.49, unadjusted) and 1.52 (95%CI 1.16–2.00, adjusted) for SUV_max, 2.07 (95%CI 1.16–3.69, unadjusted) and 1.91 (95%CI 1.13–3.22, adjusted) for MTV, and 2.47 (95%CI 1.38–4.43, unadjusted) and 1.94 (95%CI 1.12–3.33, adjusted) for TLG. Begg’s test detected publication bias, the trim and fill procedure was performed, and similar HRs were obtained. The prognostic role of SUV_max, MTV and TLG remained similar in the sub-group analyses.

Conclusions

High values of SUV_max, MTV and TLG predicted a higher risk of recurrence or death in patients with surgical NSCLC. We suggest the use of FDG PET/CT to select patients who are at high risk of disease recurrence or death and may benefit from aggressive treatments.     

Clinical Significance and Role of Lymphatic Vessel Invasion as a Major Prognostic Implication in Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Lymphatic vessel invasion (LVI) exerts an important process in the progression and local spread of cancer cells. However, LVI as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial.

Methodology/Principal Findings

A meta-analysis of published studies from PubMed and EMBASE electronic databases was performed to quantity the effects of LVI on both relapse-free survival and overall survival for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of these effects. This meta-analysis included 18,442 NSCLC patients from 53 eligible studies. LVI appeared in 32.1% (median; range, 2.8% to 70.9%) of tumor samples. In all, patients with LVI were 2.48 times more likely to relapse by univariate analysis (95% CI: 1.92–3.22) and 1.73 times by multivariate analysis (95% CI: 1.24–2.41) compared with those without LVI. For the analyses of LVI and overall survival, the pooled HR estimate was 1.97 (95% CI: 1.75–2.21) by univariate analysis and 1.59 (95% CI: 1.41–1.79) by multivariate analysis. Multivariate analysis showed a risk was 91% higher for recurrence (HR  = 1.91, 95% CI: 1.14–2.91) and 70% higher for mortality (HR = 1.70, 95% CI: 1.38–2.10) in LVI-positive I stage patients compared with LVI-negative I stage patients. Subgroup analyses showed similar significant adjusted risks for recurrence and death in adenocarcinomas, and a significant adjusted risk for death in studies that utilized elastic staining with or without immunohistochemistry in defining LVI.

Conclusions/Significance

The present study indicates that LVI appears to be an independent poor prognosticator in surgically managed NSCLC. NSCLC patients with LVI would require a more aggressive treatment strategy after surgery. However, large, well-designed prospective studies with clinically relevant modeling and standard methodology to assess LVI are required to address some of these important issues.     

Association between P16INK4a Promoter Methylation and Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Aberrant methylation of CpG islands acquired in tumor cells in promoter regions plays an important role in carcinogenesis. Accumulated evidence demonstrates P^16INK4a gene promoter hypermethylation is involved in non-small cell lung carcinoma (NSCLC), indicating it may be a potential biomarker for this disease. The aim of this study is to evaluate the frequency of P^16INK4a gene promoter methylation between cancer tissue and autologous controls by summarizing published studies.

Methods

By searching Medline, EMBSE and CNKI databases, the open published studies about P^16INK4a gene promoter methylation and NSCLC were identified using a systematic search strategy. The pooled odds of P^16INK4A promoter methylation in lung cancer tissue versus autologous controls were calculated by meta-analysis method.

Results

Thirty-four studies, including 2 652 NSCLC patients with 5 175 samples were included in this meta-analysis. Generally, the frequency of P^16INK4A promoter methylation ranged from 17% to 80% (median 44%) in the lung cancer tissue and 0 to 80% (median 15%) in the autologous controls, which indicated the methylation frequency in cancer tissue was much higher than that in autologous samples. We also find a strong and significant correlation between tumor tissue and autologous controls of P^16INK4A promoter methylation frequency across studies (Correlation coefficient 0.71, 95% CI:0.51–0.83, P<0.0001). And the pooled odds ratio of P^16INK4A promoter methylation in cancer tissue was 3.45 (95% CI: 2.63–4.54) compared to controls under random-effect model.

Conclusion

Frequency of P^16INK4a promoter methylation in cancer tissue was much higher than that in autologous controls, indicating promoter methylation plays an important role in carcinogenesis of the NSCLC. Strong and significant correlation between tumor tissue and autologous samples of P^16INK4A promoter methylation demonstrated a promising biomarker for NSCLC.     

Whole Brain Radiotherapy Plus Concurrent Chemotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: A Meta-Analysis

Objective

The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST) and toxicity in patients with brain metastases (BM) originating from non-small cell lung cancer (NSCLC) and who were treated using either whole brain radiotherapy (WBRT) plus concurrent chemotherapy or WBRT alone.

Methods

PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.

Results

In total, six randomized controlled trials (RCT) involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019) than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST) (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233) or time of neurological progression (CNS-TTP) (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543), and increased adverse events (Grade≥3) (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000). There were no significant differences in Grade 3–5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92).

Conclusion

The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.     

Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer Patients: A Meta-Analysis of 24 Studies

Objective

Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.

Methods

A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model.

Results

Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR = 1.35, 95%CI = 1.0–1.83, P = 0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR = 1.39, 95%CI = 1.07–1.81, P = 0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P = 0.014 for TR; P<0.001 for PFS).

Conclusions

XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.     

RBP2 Induces Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer

RBP2 has been found to actively participate in cancer progression. It inhibits the senescence of cancer cells, mediates cancer cell proliferation and promotes cancer metastasis. It is also essential to drug tolerance. However, the effects of RBP2 on epithelial-mesenchymal transition are still unknown. In this study, we analyzed the effects of RBP2 on epithelial-mesenchymal transition in non-small cell lung cancer. The results showed that RBP2 down-regulated the expression of E-cadherin by inhibiting the promoter activity of E-cadherin and up-regulated the expression of N-cadherin and snail via the activation of Akt signaling, and the overexpression of RBP2 induced epithelial-mesenchymal transition in non-small cell lung cancer cells. Our study further indicated thatRBP2 may be a potential target for anti-lung cancer therapy.     

Predictive Value of XPD Polymorphisms on Platinum-Based Chemotherapy in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Background

The correlation between xeroderma pigmentosum group D (XPD) polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt-chemotherapy), is still inconclusive. This meta-analysis was aimed to systematically review published evidence and ascertain the exact role of XPD polymorphisms.

Methods

Databases of MEDLINE and EMBASE were searched up to April 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according the Newcastle-Ottawa Quality Assessment Scales. The relationship between XPD polymorphisms and response to Pt-chemotherapy and survival was analyzed.

Results

A total of 22 eligible studies were included and analyzed in this meta-analysis. The overall analysis suggested that the XPD Lys751Gln polymorphism was not associated with response to Pt-chemotherapy or survival. However, the XPD 312Asn allele was significantly associated with poor response to Pt-chemotherapy compared with the Asp312 allele (Asn vs. Asp: OR = 0.435, 95% CI: 0.261–0.726). Additionally, the variant genotype of XPD Asp312Asn polymorphism was associated with favorable survival in Caucasian (AspAsn vs. AspAsp: HR = 0.781, 95% CI: 0.619–0.986) but unfavorable survival in Asian (AspAsn+AsnAsn vs. AspAsp: HR = 1.550, 95% CI: 1.038–2.315).

Conclusions

These results suggest that XPD Asp312Asn polymorphism may function as a predictive biomarker on platinum-based chemotherapy in NSCLC and further studies are warranted.     

The Value of MicroRNA-155 as a Prognostic Factor for Survival in Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Recent studies have shown that miR-155 play a positive role in the development of carcinoma. This meta-analysis aimed to identify the role of miR-155 in the survival of non-small cell lung cancer patients.

Methodology

Eligible studies were identified through database searches. Relevant data were extracted from each eligible study to assess the correlation between miR-155 expression and survival in lung carcinoma patients. The hazard ratios (HRs) and 95% confidence intervals (CIs) of the patients’ outcomes in relation to miR-155 were calculated. A total of 6 studies were included for this meta-analysis. For overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and cancer-specific survival (CSS), the combined HRs and 95% CIs were not statistically significant. Additionally, in Asian and America subgroups, greater expression levels of miR-155 were related to poor prognoses for lung cancer (HR 1.71 95% CI: 1.22–2.40, P = 0.002, HR 2.35 95% CI: 1.42–3.89 P = 0.001), while no significant relationship was present in a Europe subgroup (HR 0.75 95%CI: 0.27–2.10, P = 0.587).

Conclusions

These results suggest that miR-155 expression is not significantly related to non-small cell lung cancer patients except in patients from Asian and America.     

Vitamin D Supplementation and Breast Cancer Prevention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I² test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L.     

Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

Background

The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene.

Methods

The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted.

Results

Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger''s test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status.

Conclusion

This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.     

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.     

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

Background

The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.

Methods

Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.

Results

There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.

Conclusion

The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.