Progress of Bevacizumab in Malignant Pleural Effusion Caused by Non-small Cell Lung Cancer

Lung cancer is the most commonly diagnosed cancer worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer seriously affect the patients’ quality of life and prognosis. The management of MPE includes thoracentesis, pleurodesis, indwelling pleural catheters and drug perfusion in pleural cavity. Vascular endothelial growth factor (VEGF) and its receptor are a group of important ligands and receptors that affect angiogenesis. They are the main factors controlling angiogenesis, and they play an important role in the formation of MPE. Bevacizumab is a recombinant humanized VEGF monoclonal antibody, competitively binding to endogenous VEGF receptor. Bevacizumab can inhibit new blood vessel formation, reduce vascular permeability, prevent pleural effusion accumulation and slow the growth of cancers. This review aims to discuss the progress of bevacizumab in the treatment of MPE caused by non-small cell lung cancer (NSCLC), and explore the clinical application, efficacy, safety and future direction of bevacizumab

Progress on Neoadjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer

In recent years, there has been a consensus regarding the enhancement of prognosis in patients with advanced non-small cell lung cancer (NSCLC) through the utilization of immune checkpoint inhibitors (ICIs). Numerous clinical studies have also demonstrated the substantial value of immunotherapy for resectable NSCLC patients. Nevertheless, there remain controversies surrounding the exploration of immune combination strategies, treatment-related side effects, prognostic biomarkers, as well as other issues in the neoadjuvant therapy setting. Consequently, this article presents a comprehensive overview of the recent advancements in neoadjuvant immunotherapy for resectable NSCLC, stimulating fresh perspectives and delving into its merits and challenges in clinical application

High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis in <em>ALK</em>-Rearranged Non-Small Cell Lung Cancer

High tumour programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) after tyrosine kinase inhibitor (TKI) therapy in ALK-rearranged non-small cell lung cancer (NSCLC). However, the characteristics of the tumour microenvironment (TME) and their prognostic values in ALK-rearranged NSCLC are unknown. Here, we collected tumour tissues from pretreated ALK-rearranged NSCLC patients, immunohistochemical staining was used to assess PD-L1 expression, and tumour-infiltrating immune cells were determined via multiplex immunofluorescence staining (mIF). Our data showed that the median values of PFS for the high PD-L1 group and low PD-L1 group who received ALK-TKI treatment were 4.4 and 16.4 months, respectively (p = 0.008). The median overall survival (OS) of the two groups was 24.0 months and not reached, respectively (p = 0.021). Via univariate and multivariate analyses, a high PD-L1 expression and a worse ECOG PS were determined to be independent prognostic factors of OS (HR = 3.35, 95% CI: 1.23–9.11, p = 0.018; HR = 6.42, 95% CI: 1.45–28.44, p = 0.014, respectively). In addition, the high PD-L1 group had increased Tregs and exhausted CD8+ T cells in both the tumour and stroma (all p ALK-rearranged NSCLC. The characteristics of the TME in patients with high PD-L1 expression were shown to have an immunosuppressive status

Development and validation of the CAIL prognostic score in non‐small cell lung cancer patients with malignant pleural effusion

Abstract Background Patients with malignant pleural effusion (MPE) typically have poor prognoses, and predicting survival is challenging. The present study aimed to identify prognostic factors of overall survival (OS) in non‐small cell lung cancer (NSCLC) patients with MPE in the time of immunotherapy and targeted therapy. Methods Data of 344 consecutive NSCLC patients with MPE on clinical, radiological, and molecular characteristics and treatment options were collected. The risk factors in the training cohort were assessed using univariate and multivariate proportional hazards analyses. A clinical prognostic score was established and validated. Results According to the results of the multivariable survival analysis, the Eastern Cooperative Oncology Group (ECOG) performance score (PS), antiangiogenic therapy, immunotherapy, and lactic dehydrogenase (LDH) in pleural fluid (CAIL) prognostic score was developed (n = 275) and subsequently validated (n = 69). Patients who underwent risk stratification into low‐, moderate‐, and high‐risk groups had median OS of 46.1, 23.1, and 9.6 months, respectively (P < 0.0001). The area under the curve (AUC) analysis showed the CAIL score to be superior at predicting survival compared with the LENT score at 6 (0.84 vs. 0.77, P < 0.01), 12 (0.87 vs. 0.82, P < 0.01), and 36 months (0.80 vs. 0.77, P < 0.01). Conclusions For NSCLC patients with MPE, the validated CAIL prognostic score integrates clinical characteristics and therapeutic modalities to predict survival

DataSheet_1_Cost-Effectiveness of Pembrolizumab for the treatment of Non–Small-Cell lung cancer: A systematic review.doc

IntroductionPembrolizumab, an immune checkpoint inhibitor for treating non-small cell lung cancer (NSCLC), can impose a high financial burden. Several studies have explored the cost-effectiveness of this expensive agent. We conducted a systematic review and pooled analysis to evaluate the quality of the existing pharmacoeconomic studies on pembrolizumab strategies for NSCLC treatment as well as to conclude the cost-effectiveness of such strategies.MethodsEnglish and Chinese databases were searched to collect health economic studies on pembrolizumab therapies (monotherapy or a combination with chemotherapy) compared with chemotherapy for the treatment of NSCLC patients. The reporting quality, modeling methods, and results of incremental cost-effectiveness analysis of the included literature were descriptively analyzed.ResultsA total of 24 studies, 3 in Chinese and 21 in English, were selected. All reports satisfy a median of 31 out of 40 reporting quality assessment items based on a quality checklist for pharmacoeconomic evaluations. 12 studies used the Markov model and 11 used the partitioned survival model. A common problem identified in the modeling methods was the insufficient justification of the choices of model structure and data inputs. Pembrolizumab was found to be cost-effective in the United States and Switzerland, but not in China, France, the UK, or Singapore.ConclusionThe current cost-effectiveness studies on pembrolizumab for the treatment of NSCLC are of moderate quality, and the relevant decision-analytic modeling methods have much scope for improvement. The cost-effectiveness of pembrolizumab strategies for NSCLC varies across countries, warranting the need to pay more attention to the methodologies of pharmacoeconomic research in order to produce correct outcomes in terms of cost-effectiveness for different countries.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021250480</p

Clinical characteristics of the 10 HAFB-positive and TB-PCR-negative patients.

<p>Clinical characteristics of the 10 HAFB-positive and TB-PCR-negative patients.</p

Nucleic Acid Amplification Testing and Sequencing Combined with Acid-Fast Staining in Needle Biopsy Lung Tissues for the Diagnosis of Smear-Negative Pulmonary Tuberculosis

<div><p>Background</p><p>Smear-negative pulmonary tuberculosis (PTB) is common and difficult to diagnose. In this study, we investigated the diagnostic value of nucleic acid amplification testing and sequencing combined with acid-fast bacteria (AFB) staining of needle biopsy lung tissues for patients with suspected smear-negative PTB.</p><p>Methods</p><p>Patients with suspected smear-negative PTB who underwent percutaneous transthoracic needle biopsy between May 1, 2012, and June 30, 2015, were enrolled in this retrospective study. Patients with AFB in sputum smears were excluded. All lung biopsy specimens were fixed in formalin, embedded in paraffin, and subjected to acid-fast staining and tuberculous polymerase chain reaction (TB-PCR). For patients with positive AFB and negative TB-PCR results in lung tissues, probe assays and 16S rRNA sequencing were used for identification of nontuberculous mycobacteria (NTM). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of PCR and AFB staining were calculated separately and in combination.</p><p>Results</p><p>Among the 220 eligible patients, 133 were diagnosed with TB (men/women: 76/57; age range: 17–80 years, confirmed TB: 9, probable TB: 124). Forty-eight patients who were diagnosed with other specific diseases were assigned as negative controls, and 39 patients with indeterminate final diagnosis were excluded from statistical analysis. The sensitivity, specificity, PPV, NPV, and accuracy of histological AFB (HAFB) for the diagnosis of smear-negative were 61.7% (82/133), 100% (48/48), 100% (82/82), 48.5% (48/181), and 71.8% (130/181), respectively. The sensitivity, specificity, PPV, and NPV of histological PCR were 89.5% (119/133), 95.8% (46/48), 98.3% (119/121), and 76.7% (46/60), respectively, demonstrating that histological PCR had significantly higher accuracy (91.2% [165/181]) than histological acid-fast staining (71.8% [130/181]), <i>P</i> < 0.001. Parallel testing of histological AFB staining and PCR showed the sensitivity, specificity, PPV, NPV, and accuracy to be 94.0% (125/133), 95.8% (46/48), 98.4% (125/127), 85.2% (46/54), and 94.5% (171/181), respectively. Among patients with positive AFB and negative PCR results in lung tissue specimens, two were diagnosed with NTM infections (<i>Mycobacterium avium-intracellulare</i> complex and <i>Mycobacterium kansasii</i>).</p><p>Conclusion</p><p>Nucleic acid amplification testing combined with acid-fast staining in lung biopsy tissues can lead to early and accurate diagnosis in patients with smear-negative pulmonary tuberculosis. For patients with positive histological AFB and negative tuberculous PCR results in lung tissue, NTM infection should be suspected and could be identified by specific probe assays or 16S rRNA sequencing.</p></div

Diagnostic performance of HAFB and real-time PCR for analysis of lung biopsy specimens.

<p>Diagnostic performance of HAFB and real-time PCR for analysis of lung biopsy specimens.</p

Baseline characteristics of the study patients.

<p>Baseline characteristics of the study patients.</p