Upfront osimertinib and as sequential therapy in patients with -mutant non-small cell lung cancer (NSCLC): benefit across patients groups in a real-world retrospective cohort-the smile study.

Background: Osimertinib is the preferred first-line (L1) treatment for epidermal growth factor receptor-mutant (m) advanced non-small cell lung cancer (aNSCLC). Intensification of L1 with chemotherapy or amivantamab has shown improved outcomes at the cost of increased toxicity, raising questions about the optimal patients selection. A sequence involving first-generation tyrosine kinase inhibitor (TKI) (1G) followed by osimertinib might be considered.

Progression-Free Survival Under Immune Checkpoint Inhibitors for Metastatic Non-Small-Cell Lung Cancer: A Retrospective Cohort Study.

Introduction: Immune checkpoint inhibitors (ICI) are the standard of care for non-small-cell lung cancer (NSCLC) regardless of program death ligand-1 (PDL1) expression. However, a majority of patients presented early progression, underlining the need for better patient selection. The aim of this study was to determine effective clinical and biological biomarkers of real-world progression-free survival (rwPFS) in addition to PDL1.

Frequency of driver oncogenic alterations in NSCLC and estimated indoor radon exposure in Europe (RADON EUROPE study).

Background: Geographical variations in the frequency of oncogenic driver alterations in non-small cell lung cancer (NSCLC) are observed worldwide, likely influenced by genetic and environmental factors. Radon, a leading cause of lung cancer in nonsmokers, may influence NSCLC's molecular profile.

Objectives: This study aims to explore the potential correlation between estimated indoor radon concentrations and the frequency of driver alterations in NSCLC across Europe.

Prevalence and characteristics of lung cancer in families harboring Pathogenic Germline Variants in cancer predisposing genes: A 20-year retrospective analysis.

Introduction: Genetic predisposition for lung cancer has historically been underexplored. However, increasing evidence indicates the presence of pathogenic germline variants (PGV) in cancer predisposition genes among patients with lung cancer, highlighting a need for further investigation. Here, we report the prevalence and characteristics of lung cancer in families harboring PGVs studied in our genetic counseling unit (GCU).

Metabolic Singularities in Microsatellite-Stable Colorectal Cancer: Identifying Key Players in Immunosuppression to Improve the Immunotherapy Response.

Although immune checkpoint inhibitor (ICI) therapy is currently the standard of care in microsatellite-unstable (MSI) metastatic colorectal cancer (CRC), ICI therapy, alone or in combination with other therapies, is not a treatment approach in microsatellite-stable (MSS) CRC, which is present in 95% of patients. In this review, we focus on metabolic singularities-at the transcriptomic (either bulk or single cell), proteomic, and post-translational modification levels-that induce immunosuppression in cancer and specifically in MSS CRC. First, we evaluate the current efficacy of ICIs in limited and metastatic disease in MSS CRC.

Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.

Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y.

Validation of the Lung Immune Prognostic Index in patients with untreated advanced non-small cell lung cancer: Post hoc analysis of the IMpower 130, 131 and 150 trials.

Introduction: LIPI has been strongly correlated with immunotherapy (IT) outcomes in advanced NSCLC. Limited data is available for upfront chemotherapy (CT) + IT combinations. We aimed to study its prognostic value in 1st-line CT +/- IT +/- antiangiogenics.

The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease.

Purpose: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations.

Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection.

The C250T Mutation of Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.

Unlabelled: The aim of this study was to determine how mutations impact glioblastoma prognosis.

Materials And Methods: mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients.

Second-line treatment outcomes after progression from first-line chemotherapy plus immunotherapy in patients with advanced non-small cell lung cancer.

Introduction: Chemotherapy plus immunotherapy is the standard of care for patients with metastatic NSCLC. No study has evaluated the outcomes of second-line chemotherapy treatments after progression following first-line chemo-immunotherapy.

Method: This multicenter retrospective study evaluated the efficacy of second line (2L) chemotherapies after progression under first-line (1L) chemo-immunotherapy, measured by overall survival (2L-OS) and progression free survival (2L-PFS).

Mutational Status of and Affects Clinical Outcome in -Mutated Metastatic Colorectal Cancer.

Next-generation sequencing (NGS) provides a molecular rationale to inform prognostic stratification and to guide personalized treatment in cancer patients. Here, we determined the prognostic and predictive value of actionable mutated genes in metastatic colorectal cancer (mCRC). Among a total of 294 mCRC tumors examined by targeted NGS, 200 of them derived from patients treated with first-line chemotherapy plus/minus monoclonal antibodies were included in prognostic analyses.

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy.

Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages.

Vaccine Therapy in Non-Small Cell Lung Cancer.

Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes.

Aquaporin-4-Positive Triple-Negative Breast Cancer Presenting with Paraneoplastic Neuromyelitis Optica Spectrum Disorder.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory central nervous system disorder that preferentially affects the optic nerve and the spinal cord. Although NMOSD is more commonly an idiopathic autoimmune condition associated with antibodies against aquaporin-4 (AQP4)-IgG, the disease may also occur as a paraneoplastic syndrome in rare instances. In these cases, the expression of AQP4 by the tumor is likely the trigger of the autoimmune response.

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations.

Introduction: It has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations.

Methods: In this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations.

Pleural effusion is a negative prognostic factor for immunotherapy in patients with non-small cell lung cancer (NSCLC): The pluie study.

Background: Pleural effusion (PE) is a common metastatic site of NSCLC, associated with poor outcomes. As very few data are available about immune checkpoint inhibitors (ICI) and PE, we aimed to assess the clinical outcome of PE in NSCLC treated with ICI.

Method: Multicenter international retrospective study of patients with metastatic NSCLC treated with ICI, between 2012 and 2019.