Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy.

Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.

Expression of TILs and Patterns of Gene Expression from Paired Samples of Malignant Pleural Mesothelioma (MPM) Patients.

MPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors.

Dynamic changes in circulating tumor DNA assessed by shallow whole-genome sequencing associate with clinical efficacy of checkpoint inhibitors in NSCLC.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit.

Connection between Weather Types and Air Pollution Levels: A 19-Year Study in Nine EMEP Stations in Spain.

This study focuses on the analysis of the distribution, both spatial and temporal, of the PM (particulate matter with a diameter of 10 µm or less) concentrations recorded in nine EMEP (European Monitoring and Evaluation Programme) background stations distributed throughout mainland Spain between 2001 and 2019. A study of hierarchical clusters was used to classify the stations into three main groups with similarities in yearly concentrations: GC (coastal location), GNC (north-central location), and GSE (southeastern location). The highest PM concentrations were registered in summer.

Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer.

In recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established.

High levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC.

Background: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive.

Hepatic Rupture as the Initial Presentation of an -Mutated Lung Adenocarcinoma: A Case Report.

Hepatic rupture is a rare complication of solid tumor malignancies, notably in lung adenocarcinomas, and carries an extremely poor overall prognosis. Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma predict benefit with tyrosine kinase inhibitors (TKIs). This case report describes a female patient who presented with a metastatic hepatic rupture and was subsequently diagnosed with -mutated lung adenocarcinoma.

Trend analysis and outlier distribution of CO and CH: A case study at a rural site in northern Spain.

CO and CH outliers may have a noticeable impact on the trend of both gases. Nine years of measurements since 2010 recorded at a rural site in northern Spain were used to investigate these outliers. Their influence on the trend was presented and two limits were established.

Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort.

CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d'Hebron University Hospital between November 2002 and April 2020 were reviewed.

Genetic evolution to tyrosine kinase inhibitory therapy in patients with EGFR-mutated non-small-cell lung cancer.

Background: Tumour heterogeneity impacts the efficacy of metastatic cancer treatment even if actionable mutations are identified. Clinicians need to understand if assessing one lesion provides reliable information to drive a therapeutic decision in non-small-cell lung cancer (NSCLC) patients.

Methods: We analysed inter-tumour heterogeneity from five autopsied individuals with NSCLC-harbouring mutations in the epidermal growth factor receptor (EGFR), treated with EGFR tyrosine kinase inhibitors (TKIs).

Influence of Wind Speed on CO and CH Concentrations at a Rural Site.

Meteorological variables have a noticeable impact on pollutant concentrations. Among these variables, wind speed is typically measured, although research into how pollutants respond to it can be improved. This study considers nine years of hourly CO and CH measurements at a rural site, where wind speed values were calculated by the METEX model.

Interrelations between Patients' Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients.

Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response.

Spatial analysis and evolution of four air pollutants in England and Wales.

Pollution control is based on an exhaustive knowledge of concentration distributions. This study analyses a detailed database of NO, O, PM and PM in England and Wales over the period 2007-2011. Daily and annual means were considered in a 1-km spatial resolution.

Molecular profiling of long-term responders to immune checkpoint inhibitors in advanced non-small cell lung cancer.

Immunotherapy has transformed advanced non-small cell lung cancer (NSCLC) treatment strategies and has led to unprecedented long-lasting responses in some patients. However, the molecular determinants driving these long-term responses remain elusive. To address this issue, we performed an integrative analysis of genomic and transcriptomic features of long-term immune checkpoint inhibitors (ICIs)-associated responders.

Key Points in Air Pollution Meteorology.

Although emissions have a direct impact on air pollution, meteorological processes may influence inmission concentration, with the only way to control air pollution being through the rates emitted. This paper presents the close relationship between air pollution and meteorology following the scales of atmospheric motion. In macroscale, this review focuses on the synoptic pattern, since certain weather types are related to pollution episodes, with the determination of these weather types being the key point of these studies.

CO spatio-temporal analysis in the Iberian Peninsula.

A comparison between monthly CO values calculated in the Iberian Peninsula and those measured during six years commencing on October 2010 in the centre of its upper plateau is presented. Gaussian and Epanechnikov kernels are used to calculate CO concentration and its growth rate in the study region from values at certain grid points. Slight spatial differences are obtained, revealing that both concentration and growth rate are nearly uniform in the region.

Genomic Profiling Identifies Outcome-Relevant Mechanisms of Innate and Acquired Resistance to Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Lung Cancer.

Purpose: Third-generation epidermal growth factor receptor () tyrosine kinase inhibitors (TKIs) are effective in acquired resistance (AR) to early-generation EGFR TKIs in EGFR-mutant lung cancer. However, efficacy is marked by interindividual heterogeneity. We present the molecular profiles of pretreatment and post-treatment samples from patients treated with third-generation EGFR TKIs and their impact on treatment outcomes.

Analysis of PM10 and PM2.5 Concentrations in an Urban Atmosphere in Northern Spain.

This work analyses levels of particles PM10 and PM2.5 recorded at four air-quality monitoring stations located in the urban area of Valladolid (Spain) during 2015-2016. To achieve this, the evolution of particle concentrations at different time scales was determined.

Activity of HSP90 Inhibiton in a Metastatic Lung Cancer Patient With a Germline BRCA1 Mutation.

Heat shock proteins (HSPs) are molecular chaperones that maintain proteins in their correct conformation to ensure stability and protect carcinoma cells from apoptosis. HSP90 inhibitors (HSP90i) block multiple targets simultaneously, and despite responses in a selected population, no HSP90i have yet been approved. We present a patient with a lung tumor with an exceptional response to cisplatin/gemcitabine in combination with HSP90i, which nowadays continues with HSP90i maintenance after three years.

The influence of meteorological variables on CO and CH trends recorded at a semi-natural station.

CO and CH evolution is usually linked with sources, sinks and their changes. However, this study highlights the role of meteorological variables. It aims to quantify their contribution to the trend of these greenhouse gases and to determine which contribute most.

Immune-Related Gene Expression Profiling After PD-1 Blockade in Non-Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma.

Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS).

Temporal patterns of CO and CH in a rural area in northern Spain described by a harmonic equation over 2010-2016.

The present paper seeks to improve our knowledge concerning the evolution of CO and CH in terms of monthly trends, growth rate and seasonal variations in the lower atmosphere. Dry continuous measurements of CO and the CH mixing ratio were carried out over five and a half years (from 15 October 2010 to 29 February 2016) by multi-point sampling at 1.8, 3.

Outcome prognostic factors in inoperable malignant bowel obstruction.

Purpose: Inoperable malignant bowel obstruction (MBO), a severe complication of peritoneal carcinomatosis, has a low desobstruction rate (30-40 %) and end-of-life decision-making is hampered by the lack of known prognostic factors. This study aimed to explore prognostic factors for desobstruction in MBO.

Methods: All patients with inoperable MBO admitted in our large oncology hospital between 2010 and 2013 were treated following a clinical protocol based on antiemetics, steroids and two antisecretories, octreotide, and hyoscine butylbromide.

Influence of atmospheric stability and transport on CH4 concentrations in northern Spain.

Continuous methane (CH4) concentrations were measured in Northern Spain over two years (2011-2012) by multi-point sampling at 1.8, 3.7 and 8.