Ping Gu

Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis.

STUDY OBJECTIVESnRecently, less invasive methods have emerged as potential alternatives for staging with tissue confirmation of suspected metastatic mediastinal lymph nodes in lung cancer. The objective of this review was to assess the overall diagnostic accuracy of EBUS-TBNA in detecting metastatic mediastinal lymph node in lung cancer with a meta-analysis.nnnMETHODSnThe MEDLINE, EMBASE, Cancerlit and Cochrane Library database, from January 1995 to September 2008, were searched for studies evaluating EBUS-TBNA accuracy. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver-operating characteristic.nnnRESULTSnA total of 11 studies with 1299 patients, who fulfilled all of the inclusion criteria, were considered for the analysis. No publication bias was found. EBUS-TBNA had a pooled sensitivity of 0.93 (95% CI, 0.91-0.94) and a pooled specificity of 1.00 (95% CI, 0.99-1.00). The subgroup of patients who were selected on the basis of CT or PET positive results had higher pooled sensitivity (0.94, 95% CI 0.93-0.96) than the subgroup of patients without any selection of CT or PET (0.76, 95% CI 0.65-0.85) (p<0.05). Study sensitivity was not correlated with the prevalence of lymph node metastasis. Only two complications occurred (0.15%).nnnCONCLUSIONnEBUS-TBNA was an accurate, safe and cost-effective tool in lung cancer staging. The selection of patients who had positive results of suspected lymph node metastasis in CT or PET may improve the sensitivity of EBUS-TBNA. High-quality prospective studies regarding EBUS-TBNA in lung cancer staging are still needed to be conducted.

Transcriptional profiling revealed the anti-proliferative effect of MFN2 deficiency and identified risk factors in lung adenocarcinoma

Mitofusin-2 (MFN2) was initially identified as a hyperplasia suppressor in hyper-proliferative vascular smooth muscle cells (VSMCs) of hypertensive rat arteries, which has also been implicated in various cancers. There exists a controversy in whether it is an oncogene or exerting anti-proliferative effect on tumor cells. Our previous cell cycle analysis and MTT assay showed that cell proliferation was inhibited in MFN2 deficient A549 human lung adenocarcinoma cells, without investigating the changes in regulatory network or addressing the underlying mechanisms. Here, we performed expression profiling in MFN2 knockdown A549 cells and found that cancer-related pathways were among the most susceptible pathways to MFN2 deficiency. Through comparison with expression profiling of a cohort consisting of 61 pairs of tumor-normal matched samples from The Cancer Genome Atlas (TCGA), we teased out the specific pathways to address the impact that MFN2 ablation had on A549 cells, as well as identified a few genes whose expression level associated with clinicopathologic parameters. In addition, transcriptional factor target enrichment analysis identified E2F as a potential transcription factor that was deregulated in response to MFN2 deficiency. Although bioinformatics analysis usually entail further verification, our study provided considerable information for future scientific inquiries in related areas as well as a paradigm for characterizing perturbation in regulatory network.

Reliability of using circulating tumor cells for detecting epidermal growth factor receptor mutation status in advanced non-small-cell lung cancer patients: a meta-analysis and systematic review

Purpose To evaluate the clinical value of circulating tumor cells as a surrogate to detect epidermal growth factor receptor mutation in advanced non-small-cell lung cancer (NSCLC) patients. Methods We searched the electronic databases, and all articles meeting predetermined selection criteria were included in this study. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated. The evaluation indexes of the diagnostic performance were the summary receiver operating characteristic curve and area under the summary receiver operating characteristic curve. Results Eight eligible publications with 255 advanced NSCLC patients were included in this meta-analysis. Taking tumor tissues as reference, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating tumor cells for detecting the epidermal growth factor receptor mutation status were found to be 0.82 (95% confidence interval [CI]: 0.50–0.95), 0.95 (95% CI: 0.24–1.00), 16.81 (95% CI: 0.33–848.62), 0.19 (95% CI: 0.06–0.64), and 86.81 (95% CI: 1.22–6,154.15), respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94). The subgroup analysis showed that the factors of blood volume, histological type, EGFR-tyrosine kinase inhibitor therapy, and circulating tumor cell and tissue test methods for EGFR accounted for the significant difference of the pooled specificity. No significant difference was found between the pooled sensitivity of the subgroup. Conclusion Our meta-analysis confirmed that circulating tumor cells are a good surrogate for detecting epidermal growth factor receptor mutation when tumor tissue is unavailable in advanced NSCLC patients, but more precise techniques are needed to improve their clinical efficiency.

Coexistence of sensitive and resistant epidermal growth factor receptor (EGFR) mutations in pretreatment non-small cell lung cancer (NSCLC) patients: First or third generation tyrosine kinase inhibitors (TKIs)?

OBJECTIVESnOccasionally, primary 20 T790M/insertion plus sensitive mutations can be detected within a single tumor sample by routine molecular testing, but the optimal clinical management for these patients is unclear. Herein, we determined the optimal treatment strategy for these patients.nnnMATERIALS AND METHODSnFrom January 2011 to January 2017, patients diagnosed with epidermal growth factor receptor (EGFR) mutation were screened. For these harboring primary 20 T790M/insertion plus sensitive mutations, the effectiveness of the first or third generation tyrosine kinase inhibitors (TKIs) were retrospectively analyzed.nnnRESULTSn16,842 individuals were screened during the study period with 5900 positive patients identified. Sixty-one patients were confirmed to have primary 20 T790M/insertion plus sensitive mutations (1% of all EGFR-mutant patients, 95% CI, 0.8%-1.3%). Among them, 31 eligible patients were included for survival analyses. The median progression-free survival (PFS) of the 15 osimertinib-treated patients was 18.0 months (95% CI, 15.1-20.9 months), which was greatly longer than the 16 patients who were treated with first generation TKIs (1.2 months, 95% CI, 0.9-1.6, Pu202f<u202f0.001). Similar results were also observed in overall survival (OS) with 25.1 months (95% CI, not calculable) in the osimertinib group and 17.3 months (95% CI, 9.3-25.4 months) in the first generation TKI group (Pu202f=u202f0.02).nnnCONCLUSIONSnFor patients harboring primary resistant and sensitive mutations detected by routine clinical methods, first generation TKIs are ineffective even with the presence of sensitive mutations. However, osimertinib shows great survival benefit, and thus, should be considered during the whole clinical management.

Hepatotoxicity in Advanced Lung Adenocarcinoma: A Retrospective Study of 2108 Cases

The study aimed to identify the risk factors and frequency of hepatotoxicity in patients with advanced lung adenocarcinoma. Liver function tests were documented in 2108 patients with advanced (IIIB/IV) lung adenocarcinoma at a single institution who received first line platinum-based doublet chemotherapy. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Risk factors for hepatotoxicity were assessed using logistic regression analysis. Differences in hepatotoxicity between pemetrexed and non-pemetrexed regimens were evaluated after propensity score matching. After accounting for hepatic dysfunction during the first-line treatment, 892 patients receiving beyond first-line treatment were included in the subsequent analyses. Hepatotoxicity in beyond first-line treatment was compared between patients having epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy alone. In the first-line analysis, 316 (15.0%) patients developed liver dysfunction. Younger age (Odds Ratio [OR] 2.398, 95% Confidence Interval [95% CI] 1.755-3.275), pretreatment liver impairment (OR 2.285, 95% CI 1.622-3.220), and pemetrexed-contained chemotherapy (OR 1.835, 95% CI 1.408-2.393) were risk factors of hepatotoxicity (all P<0.001). Significant differences were observed for patients with all grades of hepatotoxicity while no differences were found concerning grade ¾ hepatotoxicity between 844 pemetrexed and 844 non-pemetrexed regimen matched cases (P<0.0001 and P=0.4220, respectively). After first-line treatment, the presence of hepatitis virus (OR 2.905, 95% CI 1.487-5.675; P=0.002) and TKI therapy (OR 2.621, 95% CI 1.809-3.798; P<0.001) were additionally associated with increased hepatotoxicity. Patients with advanced lung adenocarcinoma with younger age, pretreatment liver injury, and presence of hepatitis virus were at high risk for hepatotoxicity following chemotherapy. Pemetrexed-contained chemotherapy and TKIs should be used cautiously in patients who are susceptible to liver damage.

Efficacy of Local Consolidative Therapy for Oligometastatic Lung Adenocarcinoma Patients Harboring Epidermal Growth Factor Receptor Mutations

Background: For oligometastatic lung adenocarcinoma patients with sensitive epidermal growth factor receptor (EGFR) mutations, the role of local consolidative therapy (LCT) remains debatable. The purpose of this study was to investigate the efficacy of LCT in oligometastatic lung adenocarcinoma patients. Patients and Methods: We conducted a retrospective study to assess the effects of LCT on progression‐free survival (PFS) and overall survival (OS). Patients with advanced‐stage oligometastatic lung adenocarcinoma harboring sensitive mutation of epidermal growth factor receptor (EGFR) who received EGFR–tyrosine kinase inhibitor (TKI) or EGFR‐TKI plus LCT were admitted to Shanghai Chest Hospital from January 2010 to December 2016. The PFS and OS of the 2 groups were accordingly analyzed. Results: A total of 231 patients (143 patients who received LCT plus EGFR‐TKI [combination group] and 88 patients who only received EGFR‐TKI only [monotherapy group]) were included in this study. Median PFS was significantly longer in the combination group (15 months; 95% confidence interval [CI], 13.611‐16.389) than in the monotherapy group (10 months; 95% CI, 8.936‐11.064; hazard ratio = 0.610; 95% CI, 0.461, 0.807; P = .000). The median OS in the combination group was 34 months (95% CI, 27.889, 40.111) versus 21 months (95% CI, 18.445, 23.555) in the monotherapy group (hazard ratio = 0.593; 95% CI, 0.430‐0.817; P = .001). Conclusion: LCT combined with TKIs therapy was a feasible method that significantly improved PFS and OS among oligometastatic lung adenocarcinoma patients with EGFR mutations, and it thus might be considered as an important medical treatment during clinical management.

Primary thoracic extraskeletal osteosarcoma: a case report and literature review

Primary extraskeletal osteosarcoma (ESOS) presenting in thoracic locations is very rare and associated with a poor prognosis. The current study presents a case involving a large anterior mediastinal mass, which was histologically confirmed as a primary osteosarcoma. The literature concerning primary thoracic ESOS is reviewed. A total of 60 cases were identified. The median age was 60 years (range, 14-93 years) and males were more prevalent among the reported cases (65%). Survival analysis revealed that the overall 5-year survival was only 22.3%. The majority of cases of thoracic ESOS presented in the lung (n=24, 40%), with others presenting in the mediastinum, pleura, or chest wall. The benefit of surgery, chemotherapy and radiotherapy was confirmed by Cox regression survival analyses.