Prognostic impact of targetable driver alterations in resected early-stage lung cancer.

Background: Apart from fusions and the common mutations, targetable molecular alterations are irrelevant for adjuvant treatment decision making in early-stage non-small cell lung cancer (NSCLC). This retrospective analysis aimed to investigate if there is a difference in recurrence-free survival in stage I-III NSCLC harboring druggable molecular alterations compared to subtypes without targetable molecular alterations.

Methods: All consecutive patients who underwent surgery with curative intent for NSCLC (stage I-III) with targetable mutations between January 2015 and December 2020 at three Austrian institutions were identified and compared with tumors without targetable molecular alterations.

Soluble PD-L1 shows no association to relapse and overall survival in early stage non-small cell lung cancer (NSCLC).

Background: Cancer immune evasion is critical in non-small cell lung cancer (NSCLC) and has been targeted by immunotherapy. High soluble (s)PD-L1 is associated with reduced survival and treatment failure in advanced stages. Here we evaluated the effects of sPD-L1 on T cells, relapse free survival, and overall survival in early stage NSCLC.

Real-world Data of Palliative First-line Checkpoint Inhibitor Therapy for Head and Neck Cancer.

Background/aim: Pembrolizumab alone or combined with chemotherapy is now approved in PD-L1-positive patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Since real-world data are pending, our goal was to evaluate the efficacy and safety of immune checkpoint inhibitor (CPI) therapy in an unselected cohort of patients with SCCHN.

Patients And Methods: We analyzed 78 patients with recurrent or metastatic SCCHN from three Austrian cancer centers that received CPI therapy alone or with chemotherapy as palliative first-line systemic treatment for this retrospective study.

High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune cell infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how immune cell phenotypes vary across different patient subgroups is lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution by integrating 1,283,972 single cells from 556 samples and 318 patients across 29 datasets, including our dataset capturing cells with low mRNA content.

Molecular Characteristics of Radon Associated Lung Cancer Highlights MET Alterations.

Effective targeted treatment strategies resulted from molecular profiling of lung cancer with distinct prevalent mutation profiles in smokers and non-smokers. Although Rn is the second most important risk factor, data for Rn-dependent driver events are limited. Therefore, a Rn-exposed cohort of lung cancer patients was screened for oncogenic drivers and their survival and genetic profiles were compared with data of the average regional population.

Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission.

Objectives: We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).

Methods: Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J.

Functional Outcomes in Head and Neck Cancer Patients.

With the increase in long-term survivorship of head and neck cancer (HNC), the functional outcomes are gaining importance. We reported the functional outcomes of HNC patients using the HNC-Functional InTegrity (FIT) Scales, which is a validated tool for the rapid clinical assessment of functional status based on observable clinical criteria. Patients with newly diagnosed HNC treated at the Medical University of Innsbruck between 2008 and 2020 were consecutively included, and their status in the six functional domains of food-intake, breathing, speech, pain, mood, and neck and shoulder mobility was scored by the treating physician at oncological follow-up visits on a scale from 0 (loss of function) to 4 (full function).

Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer: systematic review and meta-analysis.

Objective: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC.

Materials And Methods: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.

Hepatobiliary Adverse Drug Reactions Associated With Remdesivir: The WHO International Pharmacovigilance Study.

Remdesivir has demonstrated clinical benefits in randomized placebo-controlled trials (RCTs) in patients with coronavirus disease 2019 (COVID-19) and was first approved for COVID-19 patients. However, whether remdesivir causes gastrointestinal adverse drug reaction (GI-ADRs) including hepatotoxicity is less clear. Therefore, we aimed to detect a diverse spectrum of GI-ADRs associated with remdesivir using VigiBase, the World Health Organization's international pharmacovigilance database of individual case safety reports.

The Epithelial-Mesenchymal Transcription Factor Slug Predicts Survival Benefit of Up-Front Surgery in Head and Neck Cancer.

EMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slug expression was determined by IHC scoring in tumor specimens from patients with incident HNSCC.

Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase.

Systematic review: Soluble immunological biomarkers in advanced non-small-cell lung cancer (NSCLC).

In the highly dynamic field of advanced malignancies, biomarkers from liquid samples are urgently needed to improve treatment tailoring. However, the heterogenic data lack direct comparison of assays, vectors and relevant validations are rarely found. Therefore, we classified the available studies based on three categories: Measured vectors, applied technique and detected biomarker.

Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies.

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018.

Statin and Cancer Mortality and Survival: An Umbrella Systematic Review and Meta-Analysis.

The aim of this study is to provide an overview and understand the strength of evidence and the extent of potential biases and the validity of claimed associations between the use of statins and cancer mortality or survival. We performed a comprehensive umbrella review of meta-analyses and systematically appraised the relevant meta-analyses of observational studies on the associations between statin use and cancer mortality or survival in various kinds of cancer. We searched the PubMed database and screened the reference list of relevant articles.

Efficacy of Cancer Immunotherapy: An Umbrella Review of Meta-analyses of Randomized Controlled Trials.

We conducted a systematic review for evidence of the clinical efficacy of cancer immunotherapies. We searched PubMed from inception to 14 February 2018 for meta-analyses of randomized controlled trials (RCTs) of cancer immunotherapies. Re-analyses were performed to estimate the summary effect size under random-effects, the 95% confidence interval (CI), heterogeneity, and the 95% prediction interval, and we determined the strength of the evidence.

Tumor Mutational Burden and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Tumor mutational burden (TMB) is a genomic biomarker that predicts favorable responses to immune checkpoint inhibitors (ICIs). Here, we set out to assess the predictive value of TMB on long-term survival outcomes in patients undergoing ICIs. We systematically searched PubMed, Embase, CENTRAL and clinicaltrials.

Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis.

Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.

Effect of Statin on Cancer Incidence: An Umbrella Systematic Review and Meta-Analysis.

Statins are reported to reduce the risk of cancer, but the results of various published studies have been contradictory. We carried out an umbrella review to provide an overview and understand the strength of evidence, extent of potential biases, and validity of claimed associations between the use of statins and cancer incidence. We comprehensively re-analyzed the data of meta-analyses of randomized controlled trials (RCTs) and observational studies on associations between statin use and cancer incidence.

ASCO 2018 NSCLC highlights-combination therapy is key.

Non-small cell lung cancer (NSCLC) treatment was booming at this year's ASCO 2018 meeting as several well-performed phase III trials with practice-changing potential were presented. Thereby immune checkpoint blockade (ICB) consolidated its major role in the treatment of NSCLC patients without genetic alterations and extended its use by showing impressive data on ICB combination therapies (mainly combined with chemotherapy). Furthermore the role of predictive biomarkers for ICB therapy (Programmed death-ligand 1 [PD-L1] expression, tumor mutational burden [TMB] testing and others) have been further developed and blood-based tests were presented with promising data revealing the potential of this minimally invasive method for treatment monitoring and guidance in the future.

Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade.

Analyzing mouse tumor models in vivo, human T cells ex vivo, and human lung cancer samples, we provide direct evidence that NR2F6 acts as an immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with established cancer immune checkpoint blockade, efficiently delays tumor progression and improves survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade reveal multiple advantageous transcriptional alterations.

3D-cultivation of NSCLC cell lines induce gene expression alterations of key cancer-associated pathways and mimic conditions.

This work evaluated gene expression differences between a hanging-drop 3D NSCLC model and 2D cell cultures and their relevance by comparison to patient-derived data from The Cancer Genome Atlas. Gene expression of 2D and 3D cultures for Colo699 and A549 were assessed using Affymetrix HuGene 1.0 ST gene chips.

Aviscumine, a recombinant ribosomal inhibitor, increases the antitumor activity of natural killer cells.

Aviscumine, a recombinant lectin I, has been identified as an immunomodulatory agent within a new class of ribotoxic stress-inducing anticancer substances that have demonstrated efficacy in phase I/II trials. The aim of the present study was to elucidate the presumed effect of aviscumine on enhancing human natural killer (NK) cell antitumor cytotoxicity. To measure the effect of aviscumine on human NK cell cytotoxicity, chromium-51-release assays against K-562 cells were performed with isolated NK cells from the whole blood of 34 healthy volunteers.

The influence of stromal cells and tumor-microenvironment-derived cytokines and chemokines on CD3CD8 tumor infiltrating lymphocyte subpopulations.

The tumor microenvironment has been identified as a major mediator of immunological processes in solid tumors. In particular, tumor-associated fibroblasts are known to interact with tumor infiltrating immune cells. We describe the influence of fibroblasts and tumor-microenvironment-derived cytokines on the infiltration capacity of CD3CD8 cytotoxic T lymphocyte subpopulations using a multicellular 3D co-culture system.