Chen Shanshan, Hua Xin, Jia Jinfang, Wu Ying, Wei Shuzhen, Xu Lu, Han Shuhua, Zhang Hongming, Zhu Xiaoli
School of Medicine, Southeast University, Nanjing, China.
Department of Respiratory Medicine, Zhongda Hospital of Southeast University, Nanjing, China.
Ann Palliat Med. 2021 Apr;10(4):3657-3672. doi: 10.21037/apm-20-1722. Epub 2021 Apr 1.
Lung cancer is a leading cause of cancer-related mortality worldwide. The purpose of our meta-analysis was to assess the risk factors for brain metastases (BM) in patients with non-small cell lung cancer (NSCLC).
Multiple databases, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang, were systematically searched to recruit relevant studies investigating the risk factors for BM in NSCLC patients. The Newcastle-Ottawa Scale was used to evaluate literature quality, and the meta-analysis was performed using the Review Manager 5.3. Evidence quality evaluation was carried out according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) standard. The estimated odds ratio (OR) and 95% confidence intervals (CIs) were set as effect measures. Funnel plots and sensitivity analyses were used to assess publication bias and the robustness and reliability of the combined results, respectively.
A total of 43 studies with 11,415 participants were included in this meta-analysis. The results indicated that the following factors were significantly associated with an increased risk of BM in NSCLC patients (P<0.05): (I) gender (female) (OR =1.32, 95% CI: 1.17-1.49, P<0.00001); (II) adenocarcinoma (OR =2.34, 95% CI: 1.76-3.11, P<0.00001) or non-squamous cell carcinoma (OR =0.63, 95% CI: 0.42-0.94, P=0.02); (III) advanced tumor stage (OR =1.48, 95% CI: 1.01-2.17, P=0.04); (IV) node stage (OR =2.19, 95% CI: 1.39-3.45, P=0.0007); (V) lymphatic metastasis (OR =2.43, 95% CI: 1.76-3.36, P<0.00001); (VI) epidermal growth factor receptor (EGFR) gene mutation (OR =1.88, 95% CI: 1.26-2.80, P=0.002); (VII) kirsten rat sarcoma viral oncogene (KRAS) gene mutation (OR =2.99, 95% CI: 1.82-4.91, P<0.00001); (VIII) higher levels of carcinoembryonic antigen (P<0.00001), carbohydrate antigen 199 (P<0.0001), cytokeratin-19 fragment (P=0.04), neuron-specific enolase (P<0.00001), and carbohydrate antigen 125 (P=0.0005).
This meta-analysis demonstrated that NSCLC patients with BM have more aggressive clinical features.
肺癌是全球癌症相关死亡的主要原因。我们进行这项荟萃分析的目的是评估非小细胞肺癌（NSCLC）患者发生脑转移（BM）的危险因素。
系统检索多个数据库，包括PubMed、EMBASE、Cochrane图书馆、中国知网（CNKI）和万方，以纳入调查NSCLC患者BM危险因素的相关研究。采用纽卡斯尔-渥太华量表评估文献质量，并使用Review Manager 5.3进行荟萃分析。根据推荐分级评估、制定与评价（GRADE）标准进行证据质量评估。设定估计比值比（OR）和95%置信区间（CI）作为效应量。分别使用漏斗图和敏感性分析评估发表偏倚以及合并结果的稳健性和可靠性。
本荟萃分析共纳入43项研究，11415名参与者。结果表明，以下因素与NSCLC患者发生BM的风险增加显著相关（P<0.05）：（I）性别（女性）（OR =1.32，95%CI：1.17-1.49，P<0.00001）；（II）腺癌（OR =2.34，95%CI：1.76-3.11，P<0.00001）或非鳞状细胞癌（OR =0.63，95%CI：0.42-0.94，P=0.02）；（III）肿瘤晚期（OR =1.48，95%CI：1.01-2.17，P=0.04）；（IV）淋巴结分期（OR =2.19，95%CI：1.39-3.45，P=0.0007）；（V）淋巴转移（OR =2.43，95%CI：1.76-3.36，P<0.00001）；（VI）表皮生长因子受体（EGFR）基因突变（OR =1.88，95%CI：1.26-2.80，P=0.002）；（VII） Kirsten大鼠肉瘤病毒癌基因（KRAS）基因突变（OR =2.99，95%CI：1.82-4.91，P<0.00001）；（VIII）癌胚抗原（P<0.00001）、糖类抗原199（P<0.0001）、细胞角蛋白-19片段（P=0.04）、神经元特异性烯醇化酶（P<0.00001）和糖类抗原125（P=0.0005）水平较高。
这项荟萃分析表明，发生BM的NSCLC患者具有更具侵袭性的临床特征。
