Sensitizing mutations in epidermal growth factor receptor (EGFR) are associated with positive responses to anti-EGFR-targeted therapy, leading to a new era of treatment for non-small cell lung cancer (NSCLC). Exon 19 deletions and exon 21 L858R substitutions are the most common mutations, accounting for approximately 90% mutations in NSCLC; these are termed classic mutations and result in high sensitivity to tyrosine kinase inhibitors (TKIs). Other EGFR mutations are termed uncommon EGFR mutations, of which G719X, S768I, L861Q, exon 20 insertions, and complex mutations are the most frequent. G719X, S768I, and L861Q are point mutations and those that exist with complex mutations are sensitive to first-generation TKIs. A prospective analysis demonstrated that afatinib, a second-generation TKI, led to a better prognosis in some patients with NSCLC compared to first-generation TKIs. Chemotherapy used to be the traditional choice for patients carrying exon 20 insertions; however, with the development of novel targeted drugs, the role of chemotherapy is changing. Tremendous progress has also been made in clinical trials on immunotherapy treatment of uncommon EGFR mutations. The treatment for patients with NSCLC harboring uncommon EGFR mutations remains a subject of debate and the sensitivity of uncommon EGFR mutations to TKIs is still unclear. Here, we summarized recent data in the literature and provide an overview of the clinical characteristics, incidence, and outcomes of patients harboring G719X, S768I, L861Q, exon 20 insertions, and complex mutations who were treated with TKIs, chemotherapy, or immunotherapy.

Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitor therapy is showing marked efficacy in advanced non-small cell lung cancer (NSCLC). Meanwhile, it is concomitant with distinctive immune-related adverse effects. We aim to describe the incidence of pneumonitis and other rare but severe immune-related adverse effects (IRAEs), as well as treatment related deaths. In addition, we analyze the differences in incidence of pneumonitis between PD-1 and PD-L1 inhibitors and standard-of-care chemotherapy. Methods: PubMed was searched up to 24 March 2017 for clinical trials of PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, avelumab and durvalumab) in treatment of NSCLC. Besides, references of relevant articles were screened. Results: Finally, 22 trials were included in our study, 14 with data of pneumonitis, 19 with other severe IRAEs or treatment related deaths and 5 with control groups. Incidence of all-grade pneumonitis was 2.9% (95% CI, 2.0–4.8%) and grade 3 or higher pneumonitis 2.0% (95% CI, 1.0–2.0%). Incidence of all-grade pneumonitis in PD-1 and PD-L1 inhibitor therapy (n=1,313) was significantly higher than that in chemotherapy (n=918) (OR=2.35, 95% CI, 1.32–4.20, P=0.004), but had no significance in grade 3–5 pneumonitis. Incidence of cardiorespiratory arrest (n=537) was 1.0% (95% CI, 0–2.0%), cardiac failure (n=214) 2.0% (95% CI, 1.0–5.7%), myocardial infarction (n=402) 1.0% (95% CI, 0–3.8%), stroke (n=135) 2.0% (95% CI, 0–13.0%), disease progression (n=391) 1.0% (95% CI, 0–2.9%), pancreatitis (n=700) 1.0% (95% CI, 0–2.0%) and severe skin reactions (n=836) 2.0% (95% CI, 1.0–3.8%). Incidence of treatment related deaths was 0.7%. Conclusions: Immune related adverse effects can on occasion be life-threatening even though usually rare. Incidence of pneumonitis in PD-1 and PD-L1 inhibitors was significantly higher than that in chemotherapy. More studies should be conducted to investigate the incidence of these rare but life-threatening IRAEs.

Clinical characteristics, laboratory abnormalities and CT findings of COVID-19 patients and risk factors of severe disease: a systematic review and meta-analysis Jingyuan Xie, Qin Wang, Yangyang Xu, Tianli Zhang, Lu Chen, Xueying Zuo, Jiaxin Liu, Litang Huang, Ping Zhan, Tangfeng Lv, Yong Song

Background: Exudative pleural effusion (EPE) is a common diagnostic challenge. The utility of medical thoracoscopy (MT) and closed pleural biopsy (CPB) to aid in the diagnosis of EPE has been reported in many published studies. Herein, we perform a systematic review and meta-analysis to compare the diagnostic yield and safety of CPB and MT in EPE. Methods: Four databases were searched for studies reporting the diagnostic yield of CPB and MT for EPE. The quality of the included studies was evaluated according to the quality assessment of diagnostic accuracy studies (QUADAS) tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and complication risks were compared between the two groups. Results: Ten studies dealing with CPB and twenty-three studies dealing with MT for the diagnosis of EPE were included in this meta-analysis. Pooled sensitivity, specificity, PLR, NLR and DOR of CPB group was 77%, 99%, 32.55, 0.22, 165.71, respectively, while pooled sensitivity, specificity, PLR, NLR and DOR of MT group was 93%, 100%, 10.82, 0.08, 162.81, respectively. The area under the summary receiver operating characteristic (SROC) curve of CPB and MT were both 0.97. The ability of CPB to diagnose non-malignant diseases was like MT (69% vs. 68%), while the ability was lower than that of MT to diagnose malignant diseases (72% vs. 92%). The pooled diagnostic accuracy of CPB and MT for mesothelioma was 26% (95% CI, 14–38%) and 42% (95% CI, 22–62%) (P<0.001), respectively. The rate of complications with CBP was lower than that reported for MT. Conclusions: CBP is a relatively accurate tool with a lower complication rate compared to MT in the diagnosis of EPE, especially in diagnosing non-malignant diseases. We confirm the utility of MT in the diagnostic workup of malignancy (especially mesothelioma); however, in selected cases, CPB could be used as the first diagnostic approach with a favorable safety profile.

Objectives: Our research aimed to evaluate the effectiveness of first‐line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive‐stage small cell lung cancer (ES‐SCLC) and identify prognostic factors, as real‐world outcomes and the inconsistency of PD‐1 and PD‐L1 inhibitors are uncertain.Methods: We selected ES‐SCLC patients in three centers and conducted a propensity score‐matched analysis. The Kaplan–Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors.Results: Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression‐free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p < 0.001). The EP plus ICIs group had a higher objective response rate (ORR) (EP: 62.3%, EP + ICIs: 84.3%, p < 0.001). Multivariate analysis presented that liver metastases (HR, 2.08; p = 0.018) and lymphocyte–monocyte ratio (LMR) (HR, 0.54; p = 0.049) were independent prognostic factors for OS, and performance status (PS) (HR, 2.11; p = 0.015), liver metastases (HR, 2.64; p = 0.002), and neutrophil‐lymphocyte ratio (NLR) (HR, 0.45; p = 0.028) were for PFS in patients with chemo‐immunotherapy.Conclusion: Our real‐world data demonstrated that ICIs with chemotherapy as the first‐line setting for ES‐SCLC are effective and safe. PS, liver metastases, and inflammatory markers could serve as valuable risk factors.

Several studies have shown the tumorigenesis role of transcriptional enhancer associate domain (TEAD) proteins; here, we initially explored expression, function and signalling mechanisms of TEAD4 in lung adenocarcinoma (LAD). Both the mRNA and protein levels of TEAD4 were increased in LAD tissues than those in adjacent nontumourous tissues. Besides, database search indicated a poorer clinical outcome in LAD patients with higher TEAD4 expression, revealing its potential tumour‐promoting role. Therefore, we conducted cellular experiments to further investigate its effect on tumour phenotypes. Accordingly, TEAD4 showed little impact on LAD cell cycle, proliferation, or apoptosis. However, silencing TEAD4 remarkably attenuated cell migration and invasion capacities. Consistently, several important epithelial‐mesenchymal transition (EMT) markers such as E‐cadherin and Slug were consequently altered by silencing TEAD4. Furthermore, we identified a novel TEAD4‐targeted microRNA, namely miR6839‐3p, and confirmed its function in suppressing TEAD4 expression. Finally, the impact of overexpressing miR6839‐3p mimics on LAD progression was validated, which showed a similar pattern with TEAD4 knockdown cells. Taken together, our data not only revealed the significant role of TEAD4 in promoting LAD progression and predicting clinical outcome but also distinguished miR6839‐3p mimics as a promising therapeutic direction.