First-line MET tyrosine kinase inhibitors versus immunotherapy ± chemotherapy for patients with MET exon 14 skipping mutant metastatic NSCLC.

Purpose: First-line treatment options for MET exon 14 skipping (METex14) mutant metastatic non-small cell lung cancer (NSCLC) vary due to differences in drug approvals and clinical experience. This study investigates factors influencing outcomes with first-line MET tyrosine kinase inhibitors (TKI) versus immune checkpoint inhibitors (ICI)±chemotherapy.

Experimental Design: Clinicopathologic data were collected from patients with metastatic METex14 mutant NSCLC receiving first-line MET TKI or ICI±chemotherapy at five centers.

Molecular characterization of NUT carcinoma: a report from the NUT carcinoma registry.

Purpose: NUT carcinoma (NC) is an underdiagnosed, poorly differentiated squamous cell cancer with a median survival of 6.7 months. Defined by NUTM1 fusions, NC enhances oncogene transcription, including MYC.

Feature Engineering Assessment of Tumor Infiltrating Lymphocytes in Lung Adenocarcinoma.

Tumor-Infiltrating Lymphocytes (TIL) are emerging as immunotherapy prognostic markers. Currently, TIL are assessed on hematoxylin and eosin (H&E)-stained slides of tumor tissue by pathologists. This approach is time-consuming, and subjected to inter-observer variability.

Unraveling the link between cholesterol and immune system in cancer: From biological mechanistic insights to clinical evidence. A narrative review.

Cholesterol and its metabolism seem to be involved not only in cancer progression but also in immune cells activity. In this comprehensive review, we summarize preclinical, translational, and clinical evidence regarding the crucial role of cholesterol and its metabolism in regulating the immune response against cancer cells, shedding light on the multifaceted mechanisms by which cholesterol influences immune cell function and anti-tumor immunity. By synthesizing findings from preclinical studies, we have elucidated the impact of cholesterol on immune cell activation, differentiation, and effector functions.

Differential impact of lipid profile according to neutrophil-to-lymphocyte ratio status in patients with advanced cancer treated with immunotherapy.

To investigate the different impact of each component of lipid profile in advanced cancer patients treated with immune checkpoints inhibitors (ICIs) according to neutrophil-to-lymphocyte ratio (NLR) value. We retrospectively collected total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL). 407 patients were enrolled.

Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers.

In recent years, poly (ADP-ribose) polymerase (PARP) inhibition has become a promising therapeutic option for several tumors, especially for those harboring a BRCA 1-2 mutation or a deficit in the homologous recombination repair (HRR) pathway. Nevertheless, to date, PARP inhibitors are still not largely used for thoracic malignancies neither as a single agent nor in combination with other treatments. Recently, a deeper understanding of HRR mechanisms, alongside the development of new targeted and immunotherapy agents, particularly against HRR-deficient tumors, traced the path to new treatment strategies for many tumor types including lung cancer and malignant pleural mesothelioma.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

Background: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown.

Methods: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED).

Development of detailed finite element models for in silico analyses of brain impact dynamics.

Background And Objective: In the last few decades, several studies have been performed to investigate traumatic brain injuries (TBIs) and to understand the biomechanical response of brain tissues, by using experimental and computational approaches. As part of computational approaches, human head finite element (FE) models show to be important tools in the analysis of TBIs, making it possible to estimate local mechanical effects on brain tissue for different accident scenarios. The present study aims to contribute to the computational approach by means of the development of three advanced FE head models for accurately describing the head tissue dynamics, the first step to predict TBIs.

The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab.

Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 - GRImT1).

Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC.

The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented.

Long-term effect of subthalamic and pallidal deep brain stimulation for status dystonicus in children with methylmalonic acidemia and GNAO1 mutation.

Status dystonicus (SD) is a rare and potentially life-threatening condition requiring intensive care management. Deep brain stimulation (DBS) has emerged as an effective treatment for SD refractory to medical management, but its application in this field is still limited. Here, we report the long-term outcome of four pediatric patients treated with DBS at the University Hospital of Padua, Italy, for SD refractory to medications.