Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

Consolidation ALK Tyrosine Kinase Inhibitors Versus Durvalumab or Observation After Chemoradiation in Unresectable Stage III ALK-Positive NSCLC.

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally.

New promises and challenges in the treatment of advanced non-small-cell lung cancer.

Targeted therapies and immunotherapies have radically improved treatment for advanced non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting oncogenic driver mutations continue to evolve over multiple generations to enhance effectiveness and tackle drug resistance. Immune checkpoint inhibitors remain integral for the treatment of NSCLCs that do not have specific actionable genetic mutations.

Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma.

Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving the understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA sequencing (scRNA-seq) to de novo identify 54 expression programs and construct a comprehensive cellular catalog of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis.

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown.

Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022.

Enterococcus faecalis OG1RF Evolution at Low pH Selects Fusidate-Sensitive Mutants in Elongation Factor G and at High pH Selects Defects in Phosphate Transport.

bacteria inhabit human and soil environments that show a wide range of pH values. Strains include commensals as well as antibiotic-resistant pathogens. We investigated the adaptation to pH stress in E.

The past, present, and future of targeted therapeutic approaches in patients with diffuse pleural mesotheliomas.

Despite our growing understanding of the genomic landscape of diffuse pleural mesotheliomas (DPM), there has been limited success in targeted therapeutic strategies for the disease. This review summarizes attempts to develop targeted therapies in DPM, focusing on the following targets being clinically explored in recent and ongoing clinical trials: vascular endothelial growth factor, mesothelin, BRCA1-associated protein 1, Wilms tumor 1 protein, NF2/YAP/TAZ, CDKN2, methylthioadenosine phosphorylase, v-domain Ig suppressor T-cell activation, and argininosuccinate synthetase 1. Although preclinical data for these targets are promising, few have efficaciously translated to benefit our patients.

Life-Threatening Myositis in a Patient With -Mutated NSCLC on Osimertinib: Case Report.

Osimertinib is the standard of care for the first-line treatment of -mutated NSCLC. We report a case of a 52-year-old woman who developed life-threatening myopathy because of treatment with osimertinib. Limited instances of myositis have been previously reported in the literature; however, none have resulted in life-threatening oropharyngeal and respiratory muscle weakness as seen in this case.

Multiple Cranial Neuropathies as the Presenting Sign in a Patient with Metastatic BRAF-Mutated Lung Adenocarcinoma with Leptomeningeal Involvement.

Leptomeningeal carcinomatosis accounts for only 4% of cases of multiple cranial neuropathies. Here, we report the case of a patient who presented with multiple synchronous cranial neuropathies. After treatment for neuroborreliosis and broad infectious workup, endobronchial ultrasound-guided mediastinal lymph node biopsy confirmed a diagnosis of metastatic BRAF-mutated lung adenocarcinoma with leptomeningeal involvement.

Prolonged Response to Pembrolizumab in Spindle Cell Squamous Cell Carcinoma Metastatic to the Central Nervous System.

Background: Cutaneous squamous cell carcinoma is a common type of skin cancer, with aggressive metastatic or locally advanced disease representing an uncommon minority of presentations. Emerging data have supported the Food and Drug Administration approval of the anti-PD1 human monoclonal antibody cemiplimab in select patients with advanced disease. However, there is limited data regarding durability of effect and generalizability of anti-PD1 effectiveness across therapies.