The value of serum Cyfra21-1 as a biomarker in the diagnosis of patients with non-small cell lung cancer: A meta-analysis

Objective: The serum level of Cyfra21-1 was always elevated in patients with nonsmall cell lung carcinoma. The aim of this meta-analysis was to evaluate the serum Cyfra21-1 as a biomarker in the diagnosis of nonsmall cell lung cancer (NSCLC). Methods: All the articles associated with serum Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline, and CNKI databases. The number of patients for true positive, false positive, false negative and true negative were extracted from each individual study. The pooled sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (−lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc) curve were calculated by MetaDiSc 1.4 software. Results: After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The pooled diagnosis sensitivity, specificity, +lr, −lr and dor were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95), 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) and 22.57 (95%CI: 13.89-36.68) respectively. The area under the sroc curve was 0.95. And significant publication bias was found in this meta-analysis (P = 0.049). Conclusion: With published data, the serum Cyfra21-1 was a useful biomarker for diagnosis of NSCLC.Objective: The serum level of Cyfra21-1 was always elevated in patients with nonsmall cell lung carcinoma. The aim of this meta-analysis was to evaluate the serum Cyfra21-1 as a biomarker in the diagnosis of nonsmall cell lung cancer (NSCLC). Methods: All the articles associated with serum Cyfra21-1 in the diagnosis of NSCLC were searched in the PubMed, Medline, and CNKI databases. The number of patients for true positive, false positive, false negative and true negative were extracted from each individual study. The pooled sensitivity, specificity, positive likely hood ratio (+lr), negative likely hood ratio (−lr), diagnosis odds ratio (dor) and summary receiver operating characteristic (sroc) curve were calculated by MetaDiSc 1.4 software. Results: After searching the databases, 17 studies with 4221 subjects were met the inclusion criteria and finally included in this meta-analysis. The pooled diagnosis sensitivity, specificity, +lr, −lr and dor were 0.72 (95% confidence interval [CI]: 0.70-0.73), 0.94 (95%CI: 0.93-0.95), 8.81 (95%CI: 6.36-12.22), 0.42 (95%CI: 0.32-0.55) and 22.57 (95%CI: 13.89-36.68) respectively. The area under the sroc curve was 0.95. And significant publication bias was found in this meta-analysis (P = 0.049). Conclusion: With published data, the serum Cyfra21-1 was a useful biomarker for diagnosis of NSCLC

A Meta-analysis of Association between MGMT Gene Promoter Methylation and Non-small Cell Lung Cancer

Backgroud and objective DNA promoter methylation of the tumor suppressor genes was one of the key mechanism for gene silence. The aim of this study is to investigate the difference of MGMT gene promoter methylation rate in tumor tissue and autologous controls (serum, normal lung tissue and bronchial lavage fluid) in patients with non-small cell lung cancer (NSCLC). Methods The databases of Medline, EMBSE, CNKI and Wanfang were searched for selection of published articles of MGMT gene promoter methylation and non-small cell lung carcinoma risk. The pooled odds ratio (OR) and percentage of MGMT for lung cancer tissue of NSCLC patients compared with normal lung tissue, plasma and the bronchial lavage fluid were pooled. Results 15 articles of association between MGMT gene promoter methylation and non small cell lung carcinoma risk were included in this meta-analysis. The combined results demonstrated the methylation rate of MGMT in NSCLC cancer tissue was 38% (95%CI: 23%-53%). For normal lung tissue, plasma and the bronchial lavage fluid were 16% (95%CI: 5%-27%), 23% (95%CI: 10%-34%) and 39% (95%CI: 23%-55%) respectively. The OR in cancer tissue was much higher than that in normal lung tissue and plasma odds ratio (OR) 3.98 (95%CI: 2.71-5.84, P0.05). Conclusions Mehtylation rate in MGMT gene promoter of cancer tissue in NSCLC patients was much higher than that in normal lung tissue and plasma, which showed a close association between NSCLC cancer and MGMT gene promoter methylation

Systematic Review of Studies of Workplace Exposure to Environmental Tobacco Smoke and Lung Cancer Risk

Background and objective It has been reported that there was a close relationship between lung cancer risk and environmental tobacco smoke at workplace. The aim of this study is to explore the relationship between workplace environmental tobacco smoke exposure and lung cancer risk among non-smoking subjects. Methods By searching Medline, CENTRAL (the Cochrane central register of controlledtrials), EMBASE, CBM, CNKI and VIP et al, we collected both domestic and overseas published documents on workplace environmental tobacco smoke exposure and lung cancer risk. Random or fixed effect models were applied to conduct systematic review on the study results, the combined odds ratio (OR) and the 95% confidence interval (CI) were calculated as well. Results 22 reports were included into the combined analysis, which indicated that 25% lung cancer risk was increased by exposing to workplace environment tobacco smoke (OR=1.25, 95%CI: 1.13-1.39, P < 0.001). For female the increased risk was 22% (OR=1.22, 95%CI: 1.05-1.42, P=0.011). For male the increased risk was 54%, but it does not reach the statistical significance (OR=1.54, 95%CI: 0.74-3.18, P=0.247). Conclusion Workplace environmental tobacco smoke exposure is an important risk factor of lung cancer risk among non-smoking subjects. Especially for non-smoking women who expose to workplace environment tobacco smoke have a close relationship with lung cancer

Effect of Amifostine in Head and Neck Cancer Patients Treated with Radiotherapy: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

<div><p>Background</p><p>Amifostine is the most clinical used chemical radioprotector, but its effect in patients treated with radiation is not consistent.</p><p>Methods</p><p>By searching Medline, CENTRAL, EMBASE, ASCO, ESMO, and CNKI databases, the published randomized controlled trials (RCTs) about the efficacy of amifostine in HNSCC patients treated with radiotherapy were collected. The pooled efficacy and side effects of this drug were calculated by RevMan software.</p><p>Results</p><p>Seventeen trials including a total of 1167 patients (604 and 563 each arm) were analyzed in the meta-analysis. The pooled data showed that the use of amifostine significantly reduce the risk of developing Grade3–4 mucositis (relative risk [RR],0.72; 95% confidence interval [CI],0.54–0.95; <i>p</i><0.00001), Grade 2–4 acute xerostomia (RR,0.70; 95%CI,0.52–0.96; <i>p</i> = 0.02), or late xerostomia (RR,0.60; 95%CI,0.49–0.74; <i>p</i><0.00001) and Grade 3–4 dysphagia (RR,0.39; 95%CI,0.17–0.92; <i>p = </i>0.03). However, subgroup analysis demonstrated that no statistically significant reduction of Grade3–4 mucositis (RR,0.97; 95% CI,0.74–1.26; <i>p</i> = 0.80), Grade 2–4 acute xerostomia (RR,0.35; 95%CI,0.02–5.44; <i>p</i> = 0.45), or late xerostomia (RR,0.40; 95%CI,0.13–1.24; <i>p</i> = 0.11) and Grade 3–4 dysphagia (RR,0.23; 95%CI,0.01–4.78; <i>p</i> = 0.35) was observed in patients treated with concomitant chemoradiotherapy. Compared with placebo or observation, amifostine does not show tumor protective effect in complete response (RR,1.02; 95%CI,0.89–1.17; <i>p</i> = 0.76) and partial response (RR,0.90; 95%CI, 0.56–1.44; <i>p</i> = 0.66). For the hematologic side effect, no statistical difference of Grade 3–4 leucopenia (RR,0.60; 95%CI,0.35–1.05; <i>p</i> = 0.07), anemia (RR,0.80; 95%CI, 0.42–1.53; <i>p</i> = 0.50) and thrombocytopenia (RR,0.43; 95%CI,0.16–1.15; <i>p</i> = 0.09) were found between amifostine and control groups. The most common amifostine related side effects were nausea, emesis, hypotension and allergic with an average incidence rate (Grade 3–4) of 5%, 6%, 4% and 4% respectively.</p><p>Conclusion</p><p>This systematic review showed that amifostine significantly reduce the serious mucositis, acute/late xerastomia and dysphagia without protection of the tumor in HNSCC patients treated with radiotherapy. And the toxicities of amifostine were generally acceptable.</p></div

A Meta-Analysis of the Relationship Between <i>RARβ</i> Gene Promoter Methylation and Non-Small Cell Lung Cancer

<div><p>Background</p><p>Hypermethylation of CpG islands in tumor suppressor gene plays an important role in carcinogenesis. Many studies have demonstrated that hypermethylation in promoter region of <i>RARβ</i> gene could be found with high prevalence in tumor tissue and autologous controls such as corresponding non-tumor lung tissue, sputum and plasma of the NSCLC patients. But with the small number subjects included in the individual studie, the statistical power is limited. Accordingly, we performed this meta-analysis to further asses the relationship of methylation prevalence between the cancer tissue and atuologous controls (corresponding non-tumor lung tissue, sputum and plasma).</p><p>Methods</p><p>The published articles about <i>RARβ</i> gene promoter hypermethyltion were identified using a systematic search strategy in PubMed, EMBASE and CNKI databases. The pooled odds ratio (OR) of <i>RARβ</i> promoter methylation in lung cancer tissue versus autologous controls were calculated.</p><p>Results</p><p>Finally, eleven articles, including 1347 tumor tissue samples and 1137 autologous controls were included in this meta-analysis. The pooled odds ratio of <i>RARβ</i> promoter methylation in cancer tissue was 3.60 (95%CI: 2.46–5.27) compared to autologous controls with random-effect model. Strong and significant correlation between tumor tissue and autologous controls of <i>RARβ</i> gene promoter hypermethylation prevalence across studies (Correlation coefficient 0.53) was found.</p><p>Conclusion</p><p><i>RARβ</i> promoter methylation may play an important role in carcinogenesis of the NSCLC. With significant methylation prevalence correlation between tumor tissue and autologous of this gene, methylation detection may be a potential method for searching biomarker for NSCLC.</p></div

Diagnosis Value of the Detection of CYFRA21-1 in Non-small Cell Lung Cancer

Background and objective Cytokeratin-19 fragment (CYFRA21-1) is a soluble protein in serum, and may be a useful circulating tumor marker. The aim of this study is to investigate the diagnostic value of the peripheral blood CYFRA21-1 in non-small cell lung cancer (NSCLC). Methods The levels of peripheral blood CYFRA21-1 were detected in 107 patients with NSCLC and 51 patients with benign pulmonary diseases by enzyme linked immunosorbent assay, and ROC curve was used to analyse the results. Results Singificant difference of peripheral blood CYFRA21-1 levels was detected between the NSCLC group and benign pulmonary disease group (χ2=47.343, P &lt; 0.001). At the threshold of 3.3 ng/mL, sensitivity and specificity of CYFRA21-1 as a serologic marker were 74.77% and 76.47%, respectively for any cancer. ROC curve showed that the under-curve area (AUC) of CYFRA21-1 was 0.813 9. There was no significant difference of CYFRA21-1 between subtypes of NSCLC (χ2=0.450, P=0.799). The peripheral blood CYFRA21-1 level was elevated significantly in the patients with extensive disease (IIIb, IV) compared with patients with limited disase (I, II, IIIb) (χ2=7.057, P=0.008). Conclusion As a tumor marker CYFRA21-1 has relative high sensitivity and specificity for the diagnosis of NSCLC. Elevated peripheral blood CYFRA 21-1 levels were usually indicated extensive disease of NSCLC

A meta-analysis of the Timing of Chest Radiotherapy in Patients with Limited-stage Small Cell Lung Cancer

Background and objective Although evidence for a significant survival benefit of chest radiotherapy has been proven, no conclusion could be drawn regarding the optimal timing of chest radiation. The aim of this study is to explore whether the timing of chest radiation may influence the survival of the patients with limited-stage small-cell lung cancer (LSSCLC) by performing a literature-based meta-analysis. Methods By searching Medline, CENTRAL (the Cochrane central register of controlled trials), CBM, and CNKI, et al, we collected both domestic and overseas published documents about randomized trials comparing different timing chest radiotherapy in patients with LS-SCLC. Early chest radiation was regarded as beginning within 30 days after the start of chemotherapy. Random or fixed effect models were applied to conduct meta-analysis on the trials. The combined odds ratio (OR) and the 95% confidence interval (CI) were calculated to estimate the mortality in 2 or 3 years and toxicity of the two treatments. The statistical heterogeneity was determined by cochran’s Chi-square test (Q test). The Begg’ test was used to determine the publication bias. Results Six trials that included a total of 1 189 patients were analyzed in the meta-analysis 587 patients were in the early radiation group and 602 patients were in the late radiation group. Considering all 6 eligible trials, the overall survival at 2/3 years was not significantly different between early and late chest radiation (OR=0.78, 95%CI: 0.55-1.05, Z=1.68, P=0.093). For the toxicity, no obvious difference was observed for early chest radiotherapy compared with late irradiation in pneumonitis (OR=1.93, 95%CI: 0.97-3.86, P=0.797), esophagitis (OR=1.43, 95%CI: 0.95-2.13, P=0.572) and thrombocytopenia (OR=1.23, 95%CI: 0.88-1.77, P=0.746), respectively. Conclusion No statistical difference was observed in 2/3 years survival and toxicity, including pneumonitis, esophagitis and thrombocytopenia, between early radiation and late radiotherapy in LS-SCLC

Modular polymer platform as a novel approach to head and neck cancer therapy.

Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics

Begg's funnel plot for assessment of publication bias.

<p>Begg's funnel plot for assessment of publication bias.</p

Subgroup analysis.

<p>Subgroup analysis.</p