ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples.

Liquid Biopsy: A Multi-Parametric Analysis of Mutation Status, Circulating Tumor Cells and Inflammatory Markers in -Mutated NSCLC.

The liquid biopsy has the potential to improve patient care in the diagnostic and therapeutic setting in non-small cell lung cancer (NSCLC). Consented patients with epidermal growth factor receptor (EGFR) positive disease (n = 21) were stratified into two cohorts: those currently receiving EGFR tyrosine kinase inhibitor (TKI) therapy (n = 9) and newly diagnosed EGFR TKI treatment-naïve patients (n = 12). Plasma genotyping of cell-free DNA was carried out using the FDA-approved cobas® EGFR mutation test v2 and compared to next generation sequencing (NGS) cfDNA panels.

Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC-a systematic review and meta-analysis.

Background: The ETOP 10-16 BOOSTER trial failed to demonstrate a progression-free survival (PFS) benefit for adding bevacizumab to osimertinib in second line. An exploratory subgroup analysis, however, suggested a PFS benefit of the combination in patients with a smoking history and prompted us to do this study.

Methods: A systematic review and meta-analysis to evaluate the differential effect of smoking status on the benefit of adding an angiogenesis inhibitor to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor therapy was carried out.

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry.

Introduction: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.

Methods: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics.

Results: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance.

Patients And Methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy.

Combined, patient-level, analysis of two randomised trials evaluating the addition of denosumab to standard first-line chemotherapy in advanced NSCLC - The ETOP/EORTC SPLENDOUR and AMGEN-249 trials.

Introduction: The efficacy of adding denosumab to standard first-line chemotherapy for advanced NSCLC patients has been evaluated in two separate randomised trials (SPLENDOUR and AMGEN-249). In this pooled analysis, we will assess the combination-treatment effect in the largest available population, in order to conclude about the potential impact of denosumab in NSCLC.

Methods: Both trials included in this combined analysis, were randomised (SPLENDOUR 1:1, AMGEN-249 2:1) multi-centre trials stratified by histology, bone metastasis, geographical region and for SPLENDOUR only, ECOG PS.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes.

The Association Between Adverse Childhood Experiences and Burnout in a Regional Sample of Physicians.

Objective: Little research has occurred in physicians on the prevalence of adverse childhood experiences (ACEs) and their potential correlation with burnout. The authors hypothesized that there would be a relationship between burnout levels and ACE scores, with physicians reporting more burnout being likely to have higher ACE scores.

Methods: Three hundred physicians completed the ten-question ACE scale and two burnout scales, the Mini-Z, and two items from the Maslach Burnout Inventory.

A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial.

Introduction: Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01).

Evaluating the Time to Palliative Care Referrals in Patients With Small-Cell Lung Cancer: A Single-Centre Retrospective Review.

Introduction: Lung cancer is a leading cause of morbidity and mortality worldwide. Patients with lung cancer may experience a plethora of symptoms, which can be debilitating and affect their quality of life. Palliative care input to manage their physical and psychological well-being is a crucial component of their oncological care.

Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial.

Background: The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation.

Early adulthood body mass index, cumulative smoking, and esophageal adenocarcinoma survival.

Background: Smoking and obesity are esophageal adenocarcinoma (EAC) risk factors. However, the same risk factors may also affect biological aggressiveness and cancer outcomes. Our study evaluated the combined effects of early-adulthood obesity and cumulative smoking on the EAC survival.

Randomized Phase III Trial of Erlotinib versus Docetaxel in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer Failing First-Line Platinum-Based Doublet Chemotherapy Stratified by VeriStrat Good versus VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS-lung Trial.

Introduction: Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC.

Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer.

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases.

Illness intrusiveness and subjective well-being in patients with glioblastoma.

Glioblastoma (GBM) is the most common adult CNS malignancy but its impact on quality of life (QOL) is poorly understood. In other patient populations, illness intrusiveness (the extent to which disease and treatment disrupts valued activities and interests) is associated with low subjective well-being, after controlling for disease and treatment variables. In this cross-sectional cohort study, we examined the relations among illness intrusiveness, disease burden, and subjective well-being in GBM.

Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland.

The 21-gene test is a validated multi-gene diagnostic test that predicts chemotherapy (CT) benefit in oestrogen receptor positive (ER+), lymph node-negative (N0) breast cancer (BC) patients (pts). Ireland was the first public health care system to reimburse this test in Europe. Study objectives were to assess the impact of this test on decision-making and to analyse the economic impact of testing.

Neoadjuvant chemoradiation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer.

Objectives: The objective of this study was to compare survival in patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT) or surgery plus neoadjuvant chemoradiation or chemotherapy (CRTS).

Methods: A retrospective analysis of 242 patients with stage IIIA (N2) NSCLC treated with curative intent between 1997 and 2007, identified 215 patients with surgically resectable disease. Overall survival outcomes were analysed using the Kaplan-Meier plots, log-rank tests and Cox proportional hazards models adjusting for age, gender, histology, smoking history and performance status.

Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder.

Background: Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease.

Case Report: We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder.

Glioblastoma treatment in the elderly in the temozolomide therapy era.

Background: optimal treatment of glioblastoma (gBM) in the elderly remains unclear. the impact of age on treatment planning, toxicity, and efficacy at a Canadian Cancer Centre was retrospectively reviewed.

Methods: glioblastoma patients treated consecutively between 2004 and 2008 were reviewed.

Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC?

Introduction: Elderly patients constitute the majority of patients with advanced non-small-cell lung cancer (NSCLC). The median age of newly diagnosed patients with lung cancer in the United States is approximately 70 years. Despite this, the elderly are significantly underrepresented in clinical trials.

Surgical resection for non-small cell lung cancer: clinical features and outcomes for a consecutive series at an Irish tertiary referral centre.

Background: Few patients diagnosed with lung cancer are still alive 5 years after diagnosis. The aim of the current study was to conduct a 10-year review of a consecutive series of patients undergoing curative-intent surgical resection at the largest tertiary referral centre to identify prognostic factors.

Methods: Case records of all patients operated on for lung cancer between 1998 and 2008 were reviewed.

Maintenance therapy in advanced non-small cell lung cancer: evolution, tolerability and outcomes.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world. Despite significant progress in early stage disease, survival rates for advanced disease remain low. Maintenance therapy is a treatment strategy that has been investigated extensively in NSCLC and has been the subject of considerable recent debate.

Impact and feasibility of a comprehensive geriatric assessment in the oncology setting: a pilot study.

Objectives: A comprehensive geriatric assessment (CGA) is an objective means of assessing the global health of older patients. While evidence suggesting its promise in improving outcome prediction in the oncology setting is growing, its benefit in guiding treatment decisions remains uncertain. We sought to determine the feasibility and impact of CGA, from a consultative geriatric-oncology service, on treatment decisions in older cancer patients.

How affordable are targeted therapies in non-small cell lung cancer?

As the treatment of non-small cell lung cancer (NSCLC) evolves to include more targeted therapies, costs of treatment have increased significantly. Advances in NSCLC treatment include longer survival duration, and in some cases, better progression-free survival and quality of life, and the potential for decreased toxicity. Through pharmacoeconomic analyses, payors seek to value the improvements in outcomes from novel therapies, and relate these improvements to their costs.