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.

Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment-A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report.

Introduction: Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.

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).

First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study.

Introduction: SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

Expanding first-line options for depression: Protocol of a pragmatic comparative effectiveness trial of yoga vs. behavioral activation (the COMPARE study).

Depression is a prevalent mental health condition in the United States and a significant cause of morbidity and mortality. The treatment guidelines for depression recommends either psychotherapy, such as behavioral activation (BA), or a second-generation antidepressant as a first-line treatment for adult patients with depression. However, many individuals with depression do not experience improvement from first-line treatments or choose not to engage in them due to stigma, cost, difficulty with access, and/or side effects.

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+).

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.

Complete Response on Larotrectinib in NTRK2 Fusion-Positive Non-Small Cell Lung Cancer.

In patients with non-small cell lung cancer (NSCLC) harboring a fusion of the neurotrophic receptor kinase (NTRK) gene 1 or 3, treatment with tropomyosin kinase (TRK) inhibitors have shown promising results, however so far no data on efficacy of these agents in patients with NSCLC and NTRK2 fusion are available. We present a case of a female patient with NTRK2-positive NSCLC with a complete ongoing response on therapy with larotrectinib, suggesting efficacy of first-generation TRK inhibitors also in NTRK2-positive NSCLC.

Association of Circulating Tumor DNA Testing Before Tissue Diagnosis With Time to Treatment Among Patients With Suspected Advanced Lung Cancer: The ACCELERATE Nonrandomized Clinical Trial.

Importance: Liquid biopsy has emerged as a complement to tumor tissue profiling for advanced non-small cell lung cancer (NSCLC). The optimal way to integrate liquid biopsy into the diagnostic algorithm for patients with newly diagnosed advanced NSCLC remains unclear.

Objective: To evaluate the use of circulating tumor DNA (ctDNA) genotyping before tissue diagnosis among patients with suspected advanced NSCLC and its association with time to treatment.

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

Background: Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status.

Methods: In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3.

Real-world outcomes using PD-1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland.

Background: Programmed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland.

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.

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium.

Introduction: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

Methods: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions.

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.

Sotorasib Shows Intracranial Activity in Patients with Mutated Adenocarcinoma of the Lung and Untreated Active Brain Metastases.

Treatment with sotorasib has shown intracranial complete responses and continued intracranial stabilization in mutated non-small-cell lung carcinoma (NSCLC) patients with previously treated, stable brain metastases in a post hoc analysis of the ongoing CodeBreaK 100 trial. We present the case of a patient with mutant adenocarcinoma of the lung with active untreated brain metastases with a nearly complete intracranial response only 6 weeks after start of sotorasib illustrating the benefit of sotorasib in patients with active, previously untreated brain metastases in mutated NSCLC.

iRECIST and atypical patterns of response to immuno-oncology drugs.

With the advent of immunotherapy as one of the keystones of the treatment of our patients with cancer, a number of atypical patterns of response to these agents has been identified. These include pseudoprogression, where the tumor initially shows objective growth before decreasing in size, and hyperprogression, hypothesized to be a drug-induced acceleration of the tumor burden. Despite it being >10 years since the first immune-oncology drug was approved, neither the biology behind these paradoxical responses has been well understood, nor their incidence, identification criteria, predictive biomarkers, or clinical impact have been fully described.

C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer.

Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a predictive on-treatment biomarker. In a retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, early CRP kinetics were stratified after the start of immunotherapy until weeks 4, 6, and 12 as follows: an early doubling of baseline CRP followed by a drop below baseline (CRP flare-responder), a drop of at least 30% below baseline without prior flare (CRP responders), or those who remained as CRP non-responders.

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.

Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.

Background: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.

Concurrent Chemoradiation With or Without Durvalumab in Elderly Patients With Unresectable Stage III NSCLC: Safety and Efficacy.

Introduction: The addition of durvalumab after chemoradiation therapy (CRT) in unresectable stage III NSCLC significantly improves survival. The benefit of this approach in elderly patients is controversial given the toxicity associated with CRT and, thus, may be underutilized. We sought to investigate the outcomes of elderly patients treated with CRT without or without durvalumab at our center.