Randomized Evaluation of the PET-Adjusted IMRT for NSCLC Trial (REPAINT).

Background: Standard radiotherapy (RT) for locally advanced NSCLC (LA-NSCLC) employs a uniform dose of approximately 60 Gy. Recent trials demonstrated that radiotherapy dose escalation may not improve outcomes and may cause added toxicity. XXX previously performed a single-arm trial testing a personalized, risk-adapted, and de-intensified RT strategy.

Transcriptomic Profiling and Tumor Microenvironment Classification Reveal Unique and Dynamic Immune Biology in HIV-Associated Kaposi Sarcoma.

Kaposi Sarcoma (KS) is a vascular tumor originating from endothelial cells and is associated with human herpesvirus 8 (KSHV) infection. It disproportionately affects populations facing health disparities. Although antiretroviral therapy (ART) has improved KS control in people with HIV (PWH), treatment options for advanced KS remain limited.

Surgery for Patients With cT3/4N2M0, Stage IIIB NSCLC. Is It Time to Redefine Resectability?

Introduction: Chemoradiation followed by durvalumab is considered a standard approach for patients with locally advanced NSCLC. With improvements in perioperative and neoadjuvant approaches, there is renewed interest in offering surgery to carefully selected patients with cT3/4N2 stage IIIB cancer. We sought to assess survival outcomes after surgery as part of a multimodality treatment regimen for these patients.

Smoking carcinogen induced inflammation promotes lung carcinogenesis via IRAK4 activation.

Purpose: Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, Nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(α)pyrene (BaP) have not been tested in models that mimic inhaled exposure for prolonged periods of time.

Experimental Design: ICR mice were treated with intratracheal delivery of NNK and BaP (NB) for 18 months.

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.

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ERO1A levels are a prognostic indicator in EGFR mutated non small cell lung cancer.

We have identified endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) as a poor prognostic indicator in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (EGFR-NSCLC). In addition, comparison of high versus low ERO1A expression among cohorts of EGFR-NSCLC primary samples revealed that ERO1A expression correlated with increased expression of proteins that regulate secretion. Using the CPTAC proteomic data set in lung adenocarcinoma we found that high ERO1A protein expression correlated with both extracellular matrix and matrix modifying enzymes.

Untapping the Prognostic Value of Patient-Generated Health Data in Locally Advanced Non-small Cell Lung Cancer.

Background: Patient-generated health data (PGHD), which includes patient-reported outcomes (PROs) and wearable device data, may have prognostic value for cancer patients. We tested that hypothesis using data from several prospective trials where patients with locally advanced non-small cell lung cancer (LA-NSCLC) were treated with definitive chemoradiotherapy.

Methods: Cox proportional hazards models were utilized to identify the baseline patient-reported symptom that best predicted progression-free survival (PFS) duration in a trial that involved PRO-CTCAE collection (Cohort 1).

Molecular profiling METex14+ non-small cell lung cancer (NSCLC): Impact of histology.

Objectives: MET exon 14 skipping alterations (METex14+) represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) with distinct biological and genomic features. We characterized this heterogeneity in a large cohort, integrating genomic and transcriptomic profiling with clinical outcomes, to elucidate the histologic and molecular traits and survival patterns of METex14+ NSCLC.

Materials And Methods: NSCLC tissue samples (n = 28,739) underwent DNA-based next-generation sequencing (592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-sequencing including whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 IHC (Dako 22C3) at Caris Life Sciences.

Aurora Kinase A Inhibition Potentiates Platinum and Radiation Cytotoxicity in Non-Small-Cell Lung Cancer Cells and Induces Expression of Alternative Immune Checkpoints.

Despite major advances in non-small-cell lung cancer (NSCLC) treatment, the five-year survival rates for patients with non-oncogene-driven tumors remain low, necessitating combinatory approaches to improve outcomes. Our prior high-throughput RNAi screening identified Aurora kinase A (AURKA) as a potential key player in cisplatin resistance. In this study, we investigated AURKA's role in platinum and radiation sensitivity in multiple NSCLC cell lines and xenograft mouse models, as well as its effect on immune checkpoints, including PD-L1, B7x, B7-H3, and HHLA2.

Calls to action on lung cancer management and research.

Lung cancer, the leading cause of cancer-related deaths globally, remains a pressing health issue despite significant medical advances. The New York Lung Cancer Foundation brought together experts from academia, the pharmaceutical and biotech industries as well as organizational leaders and patient advocates, to thoroughly examine the current state of lung cancer diagnosis, treatment, and research. The goal was to identify areas where our understanding is incomplete and to develop collaborative public health and scientific strategies to generate better patient outcomes, as highlighted in our "Calls to Action.

Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors.

Background: TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach.

Methods: Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ).

Skin autofluorescence, a measure for accumulation of advanced glycation end products, positively associates with blood neutrophil and monocyte counts in the general population, and particularly in men with prediabetes.

Background And Aims: Previous studies have shown that skin autofluorescence (SAF), measured with an advanced glycation end product (AGE) reader, estimates the accumulation of AGEs in tissues. SAF is predictive of incident type 2 diabetes, cardiovascular disease (CVD), and CV mortality in the general population. Studies in diabetic mice have shown that activation of the receptor for AGEs in hematopoietic progenitor cells increases blood neutrophils and monocytes, impairing atherosclerosis regression.

Real-world outcomes on platinum-containing chemotherapy for -mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors.

Background: Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered.

Pembrolizumab Plus Chemotherapy for Metastatic NSCLC With Programmed Cell Death Ligand 1 Tumor Proportion Score Less Than 1%: Pooled Analysis of Outcomes After Five Years of Follow-Up.

Background: We report long-term outcomes from a pooled analysis of patients with previously untreated metastatic NSCLC with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) less than 1% enrolled in phase III studies of pembrolizumab plus chemotherapy versus placebo plus chemotherapy.

Methods: This exploratory pooled analysis included individual patient data from the KEYNOTE-189 global (NCT02578680) and Japan extension (NCT03950674) studies of metastatic nonsquamous NSCLC without EGFR or ALK alterations and the KEYNOTE-407 global (NCT02775435) and People's Republic of China extension (NCT03875092) studies of metastatic squamous NSCLC. Patients received pembrolizumab or placebo plus pemetrexed and cisplatin or carboplatin in KEYNOTE-189 and pembrolizumab or placebo plus carboplatin and paclitaxel or nab-paclitaxel in KEYNOTE-407.

Perioperative Immunotherapy for Non-Small Cell Lung Cancer: Practical Application of Emerging Data and New Challenges.

Immune checkpoint inhibition, with or without chemotherapy, is an established standard of care for metastatic non-small cell lung cancer (NSCLC). For locally advanced NSCLC treated with chemoradiotherapy, consolidation immunotherapy has dramatically improved outcomes. Recently, immunotherapy has also been established as a valuable component of treatment for resectable NSCLC with pembrolizumab, atezolizumab, and nivolumab all approved for use in this setting.

Apolipoprotein(a) production and clearance are associated with plasma IL-6 and IL-18 levels, dependent on ethnicity.

Background And Aims: High plasma lipoprotein (a) [Lp(a)] levels are associated with increased atherosclerotic cardiovascular disease (ASCVD), in part attributed to elevated inflammation. High plasma Lp(a) levels inversely correlate with apolipoprotein (a) [(APO(a)] isoform size. APO(a) isoform size is negatively associated with APO(a) production rate (PR) and positively associated with APO(a) fractional catabolic rate (FCR).

Canakinumab in combination with docetaxel compared with docetaxel alone for the treatment of advanced non-small cell lung cancer following platinum-based doublet chemotherapy and immunotherapy (CANOPY-2): A multicenter, randomized, double-blind, phase 3 trial.

Objectives: Canakinumab, an interleukin-1 beta inhibitor, previously showed reduced lung cancer incidence and mortality (CANTOS). Here, we compare the efficacy/safety of canakinumab versus placebo in patients with advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based doublet chemotherapy (PDC) and immunotherapy.

Materials And Methods: CANOPY-2, a randomized, double-blind, phase 3 trial, enrolled adult patients with stage IIIB/IV NSCLC, without EGFR or ALK alterations, who had received one prior PDC regimen and one prior programmed death-1/programmed death-ligand 1 inhibitor and experienced subsequent disease progression.

Influence of Comutation on the Tumor Immune Microenvironment and Clinical Outcomes With Immune Checkpoint Inhibitors in -Mutant Non-Small-Cell Lung Cancer.

Purpose: Non-small-cell lung cancer (NSCLC) with has inferior outcomes to immune checkpoint inhibitors (ICIs). Using multiomics, we evaluated whether a subtype of NSCLC with a uniquely inflamed tumor immune microenvironment (TIME) harboring comutations could have favorable outcomes to ICIs.

Patients And Methods: NSCLC tumors (N = 16,896) were analyzed by next-generation sequencing (DNA-Seq/592 genes).