Temozolomide plus whole brain radiotherapy for the treatment of non-small-cell lung cancer patients with brain metastases: A protocol of an updated systematic review and meta-analysis.
- 作者列表："Duan H","Zheng SY","Zhou T","Cui HJ","Hu KW
INTRODUCTION:Whole brain radiotherapy (WBRT) has been the mainstay treatment of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients for years. Temozolomide (TMZ) could penetrate the blood-brain barrier and some studies showed that TMZ plus MBRT may improve clinical effectiveness. This meta-analysis is aim to evaluate the clinical effectiveness and safety of TMZ plus MBRT in the NSCLC patients with BM. METHODS AND ANALYSIS:We systematically searched databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database) without language restrictions from inception until July 26, 2019. Randomized controlled trials (RCTs) which compared TMZ plus WBRT with single WBRT in the advanced NSCLC patients with BM were included. The outcomes analysis reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), quality of life (QOL), and adverse effects. Two reviewers will independently extract data from the selected studies and assess the quality of studies. Statistical analyses will be performed using Review manager 5.3 software. Random-effects or fixed models were used to estimate pooled hazard ratio and relative risk. RESULTS:This systemic review and meta-analysis will evaluate the effects of TMZ plus MBRT in the NSCLC patients with BM in RCTs. CONCLUSION:Our study will provide evidence to judge if TMZ plus MBRT are effective treatment for NSCLC patients with BM.
引言: 全脑放疗 (WBRT) 多年来一直是非小细胞肺癌 (NSCLC) 患者脑转移 (BM) 的主要治疗方法。替莫唑胺 (TMZ) 可以穿透血脑屏障，一些研究表明TMZ加MBRT可以提高临床疗效。本荟萃分析旨在评估TMZ联合MBRT治疗合并BM的NSCLC患者的临床有效性和安全性。 方法和分析: 我们系统检索了包括PubMed、EMBASE、Cochrane中心对照试验注册数据库和四个中文数据库 (中文生物医学数据库、中国国家知识基础设施、万方数据库和中文科技期刊数据库) 自创刊至 2019 年 7 月 26 日无语言限制。纳入在BM晚期NSCLC患者中比较TMZ加WBRT与单一WBRT的随机对照试验 (rct)。结局分析报告客观缓解率 (ORR) 、疾病控制率 (DCR) 、总生存期 (OS) 、无进展生存期 (PFS) 、生活质量 (QOL) 、和不良反应。两名评价者将独立地从选定的研究中提取数据并评估研究的质量。将使用Review manager 5.3 软件进行统计分析。随机效应或固定模型用于估计合并风险比和相对风险。 结果: 本系统评价和荟萃分析将在RCTs中评价TMZ加MBRT在合并BM的NSCLC患者中的作用。 结论: 本研究将为TMZ联合MBRT治疗NSCLC合并BM患者的疗效判断提供依据。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.