Gene copy deletion of STK11, KEAP1, and SMARCA4: clinicopathologic features and association with outcomes to immunotherapy +/- chemotherapy in nonsquamous non-small cell lung cancer.

Background: Mutations in STK11, KEAP1, and SMARCA4 predispose to inferior immune checkpoint inhibitor (ICI) efficacy in non-small cell lung cancer (NSCLC), particularly among KRAS-mutant cases. However, the frequency, clinicopathologic features, and clinical impact of deletions in these genes are poorly characterized.

Methods: Clinicopathologic correlates of STK11, KEAP1, and SMARCA4 deletion were analyzed in nonsquamous NSCLCs at Dana-Farber Cancer Institute (DFCI).

Conjunctive optimal operation of water and power networks.

Water distribution systems (WDSs) are designed to convey water from sources to consumers. Their operation is a main concern for engineers, researchers, and practitioners and is subject to demand, pressure, and quality constraints. Pumping stations require power to pump water and keep system pressure at a desired level.

Response to Crizotinib After Entrectinib Resistance in -Rearranged, -Amplified Lung Adenocarcinoma.

Crizotinib successfully overcomes MET amplification in ROS1-rearranged NSCLC after entrectinib failure.

MET alterations as resistance mechanisms of dabrafenib-trametinib in BRAF p.V600E mutated non-small cell lung cancer patient.

The combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab.

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.

Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors.

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α.

Intrapatient variation in PD-L1 expression and tumor mutational burden and the impact on outcomes to immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer.

Background: Programmed death receptor ligand 1 (PD-L1) tumor proportion score (TPS) and tumor mutational burden (TMB) are key predictive biomarkers for immune checkpoint inhibitor (ICI) efficacy in non-small-cell lung cancer (NSCLC). Data on their variation across multiple samples are limited.

Patients And Methods: Patients with NSCLC and multiple PD-L1 TPS and/or TMB assessments were included.

Additional impact of genetic ancestry over race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer.

The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC.

Association of Baseline Tumor-Specific Neoantigens and CD8 T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors.

Purpose: Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs.

Methods: Leveraging the US Food and Drug Administration Adverse Event Reporting System, we extracted cases of suspected irAEs to calculate the reporting odds ratios (RORs) of irAEs for cancers treated with immune checkpoint inhibitors (ICIs).

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease.

Amplification of Wild-Type Represents a Novel Molecular Subtype of Several Cancer Types With Clinical Response to Selpercatinib.

Purpose: rearrangements and activating point mutations represent targetable genomic alterations in advanced solid tumors. However, the frequency and clinicopathologic characteristics of wild-type amplification in cancer and its potential role as a targetable oncogenic driver are not well-characterized.

Methods: In two institutional cohorts of patients with solid cancers from the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC) whose tumors underwent next-generation sequencing (NGS), the frequency and clinicopathologic features of wild-type amplification in the absence of rearrangements or activating mutations was assessed.

Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer.

There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.

Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed.

Materials And Methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes.

Results: At a median follow-up of 32.

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.

Clinical and Molecular Features of Long-term Response to Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer.

Purpose: We sought to identify features of patients with advanced non-small cell lung cancer (NSCLC) who achieve long-term response (LTR) to immune checkpoint inhibitors (ICI), and how these might differ from features predictive of short-term response (STR).

Experimental Design: We performed a multicenter retrospective analysis of patients with advanced NSCLC treated with ICIs between 2011 and 2022. LTR and STR were defined as response ≥ 24 months and response < 12 months, respectively.

Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC.

Introduction: Although gene-level copy number alterations have been studied as a potential biomarker of immunotherapy efficacy in NSCLC, the impact of aneuploidy burden and chromosomal arm-level events on immune checkpoint inhibitor (ICI) efficacy in NSCLC is uncertain.

Methods: Patients who received programmed cell death protein 1 or programmed death-ligand 1 (PD-L1) inhibitor at two academic centers were included. Across all 22 chromosomes analyzed, an arm was considered altered if at least 70% of its territory was either gained or deleted.

Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non-Small Cell Lung Cancer.

Purpose: ATM is the most commonly mutated DNA damage and repair gene in non-small cell lung cancer (NSCLC); however, limited characterization has been pursued.

Experimental Design: Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations.