Health Utility and Symptom Scores in Patients With Advanced Malignant Pleural Mesothelioma Treated in a Real-World Setting.

Introduction: There is a paucity of real-world associations between EQ-5D-generated health utility scores (HUS), symptoms as measured by the Edmonton Symptom Assessment System (ESAS), and the patient-reported outcomes version of the common terminology criteria for adverse events (pro-CTCAE), and survival in patients with advanced Malignant Pleural Mesothelioma (aMPM).

Methods: Clinico-demographic variables and treatment information were captured retrospectively in patients diagnosed with aMPM between January 2004 and February 2021 at Princess Margaret Cancer Centre. Quality of life outcomes were measured using HUS, ESAS, and pro-CTCAE scales, by stable versus progressive disease and line-of-treatment states.

Naturally transmitted mouse viruses highlight the heterogeneity of virus transmission dynamics in the dirty mouse model.

Unlabelled: Specific-pathogen-free (SPF) mice are widely used in biomedical research to model human infections. However, these animals do not always accurately recapitulate human immune responses. This is due, in part, to their lack of infection history.

Real-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors.

Background: Anaplastic lymphoma kinase inhibitors (ALKi) are a mainstay of therapy for patients with advanced non-small cell lung cancers (NSCLC). ALKi are associated with increased serum creatinine, which may represent reduced renal tubular creatinine secretion and/or true acute kidney injury (AKI).

Methods: We performed a retrospective study of patients who received ALKi for NSCLC (2013-2022).

Prognostic and predictive effects of TP53 co-mutation in patients with non-small cell lung cancer with rare treatable driver mutations.

Background: TP53 mutations (TP53-MUT) are common in NSCLC and have been reported as predictive of response and prognostic of poor outcome in EGFR-mutant NSCLC. The impact of TP53-MUT in NSCLCs with rarer driver mutations and approved targeted treatments is unclear.

Methods: Records of 436 patients were reviewed and associations between TP53 status, demographics, and outcomes (overall response [ORR], survival [OS] and progression-free survival [PFS], and incidence of brain metastases [BM]), were investigated.

Myasthenia Gravis in Patients Treated With Immune Checkpoint Inhibitors.

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes significantly for patients across multiple tumor types, and now are being used in combination with other therapies and in earlier settings where treatment intent is curative. Immune-related adverse events occur commonly and there are clear guidelines regarding management. Neurological toxicities such as myasthenia gravis (MG) with or without myositis are rare but are associated with high morbidity and mortality.

Retrospective cohort study assessing clinical outcomes of patients with extensive-stage small cell lung cancer treated with and without consolidative thoracic radiotherapy at the Princess Margaret Cancer Centre.

Objectives: Most patients with small cell lung cancer present with extensive-stage (ES-SCLC) disease. An international randomised trial demonstrated a survival benefit in patients treated with consolidative thoracic radiotherapy (cTRT). We report our institutional experience with this regimen.

Real-world outcomes of prophylactic cranial irradiation utilization and efficacy for patients with extensive-stage small cell lung cancer treated with consolidative thoracic radiotherapy.

Background: The role of prophylactic cranial irradiation (PCI) is not well-defined in extensive-stage SCLC (ES-SCLC), with conflicting results from randomized trials and a lack of relevant data for patients who received consolidative thoracic radiotherapy (CTRT). We sought to evaluate the impact of PCI on the outcomes of ES-SCLC patients who were all treated with CTRT.

Methods: A retrospective analysis of ES-SCLC patients without brain metastases who were all treated with CTRT between 2013-2021 at our institution was conducted.

Assessing the feasibility and external validity of natural language processing-extracted data for advanced lung cancer patients.

Background: Manual extraction of real-world clinical data for research can be time-consuming and prone to error. We assessed the feasibility of using natural language processing (NLP), an AI technique, to automate data extraction for patients with advanced lung cancer (aLC). We assessed the external validity of our NLP-extracted data by comparing our findings to those reported in the literature.

Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses.

Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known.

Analysis of outcomes in resected early-stage NSCLC with rare targetable driver mutations.

Background: Given advancements in adjuvant treatments for non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)-targeted therapies, it is important to consider postoperative targeted therapies for other early-stage oncogene-addicted NSCLC. Exploring baseline outcomes for early-stage NSCLC with these rare mutations is crucial.

Objectives: This study aims to assess relapse-free survival (RFS) and overall survival (OS) in patients with resected early-stage NSCLC with rare targetable driver mutations.

Adaptive Universal Principles for Real-world Observational Studies (AUPROS): an approach to designing real-world observational studies for clinical, epidemiologic, and precision oncology research.

The field of precision oncology has witnessed several advances that stimulated the development of new clinical trial designs and the emergence of real-world data (RWD) as an important resource for evidence generation in healthcare decision-making. Here, we highlight our experience with an innovative approach to a set of Adaptive, Universal Principles for Real-world Observational Studies (AUPROS). To demonstrate the utility of these principles, we used a mixed-methods approach to assess three studies that follow AUPROS at Princess Margaret Cancer Centre: (1) Molecular Epidemiology of ThorAcic Lesions (METAL), (2) Translational Head And NecK Study (THANKS), and (3) CAnadian CAncers With Rare Molecular Alterations (CARMA; NCT04151342).

Outcomes with non-small cell lung cancer and brain-only metastasis.

Background: We evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status.

Methods: We analyzed clinico-demographic, treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+).

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.

Experimental viral spillover across 25 million year gap in Rodentia reveals limited viral transmission and purifying selection of a picornavirus.

When a virus crosses from one host species to another, the consequences can be devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here, we present a new model of cross-species transmission where deer mice () are exposed to the natural virome of pet store mice ().

Repeat Next-Generation Sequencing (15-Gene Panel) in Unifocal, Synchronous, and Metachronous Non-Small-Cell Lung Cancer-A Single-Center Experience.

In advanced non-squamous non-small-cell lung cancer (NSCLC), routine testing with next-generation sequencing (NGS) is recommended to identify actionable genomic alterations (AGAs). The therapeutic implications of repeated NGS testing on synchronous and metachronous tumors are unclear. Between February 2017 and October 2020, NSCLC samples from a single institution were reflex-tested using a targeted 15-gene NGS panel (TruSight Tumor 15, Illumina).

Treatment patterns and outcomes in KRAS-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study.

Objectives: KRAS mutations, particularly KRAS, are prevalent in non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICIs) have been a frontline treatment, but recently developed KRAS-selective inhibitors, such as sotorasib, present new therapeutic options. We conducted a multi-center retrospective cohort study to gain insights into real-world treatment patterns and outcomes in patients with KRAS-positive advanced NSCLC receiving systemic therapy post-ICI treatment.

Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics.

Immediate Versus Deferred Systemic Therapy in Patients With Mesothelioma.

Background: The 2018 ASCO pleural mesothelioma (PM) treatment guideline states that "a trial of expectant observation may be offered" in patients with asymptomatic inoperable epithelioid mesothelioma with low disease burden. The aim of our analysis was to evaluate clinical characteristics and outcomes in PM-patients managed with initial observation and deferred treatment initiation.

Methods: We retrospectively collected clinicodemograhic and outcome data of patients with inoperable PM.

Real-World Outcomes of Patients with Advanced Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer in Canada Using Data Extracted by Large Language Model-Based Artificial Intelligence.

Real-world evidence for patients with advanced -mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study's objective was to use previously validated DARWEN artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination.

Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience.