Programmed Cell Death-Ligand 1 Expression and Clinical Outcomes Among Patients with Resected, Early-Stage Non-Small Cell Lung Cancer: A Real-World Study.

Treatment options for non-small cell lung cancer (NSCLC) are evolving, given recent and expected approvals of immune checkpoint inhibitors (ICIs) targeting programmed cell death-(ligand) 1 (PD-1/PD-L1). We retrospectively evaluated outcomes among patients with resected stage IB-IIIA NSCLC tumors expressing PD-L1 using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2016-2019). Key outcomes included PD-L1 expression rate and treatment patterns, recurrence, and median overall (mOS) and disease-free survival (mDFS) among PD-L1+ patients.

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).

Identifying Novel Germline Mutations and Copy Number Variations in Patients With SCLC.

Introduction: SCLC has traditionally been considered to arise from toxic exposure factors, such as smoking. Recent evidence has revealed that germline mutations may also affect the development of SCLC; however, these alterations remain understudied. We sought to identify novel germline mutations in SCLC including germline copy number variations (CNVs) in our cohort of patients.

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+).

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.

Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

Background: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation.

Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.

Introduction: Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors but can also often lead to immune-related adverse events (irAEs). Predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Using data from 1,327 patients with lung cancer treated with ICIs between 2009 and 2022 at four academic medical centers, we evaluated the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.

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.

Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis.

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRS) and UC (PRS) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients.

Presentation and outcomes of KRAS mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRAS-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history.

Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer.

Background: Cetuximab is a standard of care therapy for patients with RAS wild-type (WT) advanced colorectal cancer. Limited data suggest a wide variation in cetuximab plasma concentrations after standard dosing regimens. We correlated cetuximab plasma concentrations with survival and toxicity.

Cell-free DNA methylation-defined prognostic subgroups in small-cell lung cancer identified by leukocyte methylation subtraction.

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq.

Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

Objectives: This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs.

Materials And Methods: Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively.

Treatment patterns and outcomes in early-stage ALK-rearranged non-small cell lung cancer.

Introduction: We evaluated the baseline demographics, treatment patterns, and outcomes of patients with ALK-rearranged early stage (Stage I-III) non-small cell lung cancer (NSCLC). We also evaluated the efficacy and toxicity of durvalumab consolidation treatment in patients with ALK-rearranged unresectable stage III disease.

Methods: Retrospective chart-review analysis of all patients with histologically confirmed stage I-III reflexively tested ALK-rearranged NSCLC managed with curative intent at two Canadian Centers.

Treatment Patterns and Outcomes of Patients With Advanced Pleural Mesothelioma at an Academic Referral Centre.

Background: Overall survival (OS) for malignant pleural mesothelioma (MPM) in vulnerable subgroups remains poorly understood with scarce data available to guide treatment decisions. The study describes real-world detailed treatment patterns and outcomes of patients with advanced MPM overall and specifically in elderly and poor performance status (PS) patients.

Methods: Retrospective chart review was performed for all patients with histologically confirmed MPM seen at University Health Network/Princess Margaret Cancer Centre (UHN-PM).

Incidence and Clinical Features of TRPV4-Linked Axonal Neuropathies in a USA Cohort of Charcot-Marie-Tooth Disease Type 2.

Mutations in TRPV4 are linked to a group of clinically distinct, but also overlapping axonal neuropathies, including Charcot-Marie-Tooth disease type 2C (CMT2C), scapuloperoneal spinal muscular atrophy, and congenital distal spinal muscular atrophy. The incidence of TRPV4-linked cases ranges from 0 to 7% in overall axonal neuropathy cohorts from European countries and Australia. However, the data from other areas remain largely unknown.