Lung cancer : journal of the International Association for the Study of Lung Cancer
-
Review Meta Analysis
Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: a systematic review and meta-analysis of clinical trials.
Gefitinib and erlotinib are oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) widely used in advanced non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) events have been described with these agents, although the overall risk remains unclear. We performed a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of gefitinib and erlotinib. ⋯ Treatment with EGFR TKIs gefitinib and erlotinib is associated with a significant increase in the risk of developing both all-grade and fatal ILD events in advanced NSCLC.
-
ROS1 proto-oncogene translocations define a new molecular subgroup in non-small cell lung cancers (NSCLC) and are associated with a response to the MET/ALK inhibitor, crizotinib. These rearrangements are described in 0.9-1.7% NSCLC, in wild-type EGFR, KRAS and ALK ("triple negative") lung adenocarcinomas. Rapid and efficient identification of these alterations is thus becoming increasingly important. ⋯ Our results show that a screening algorithm based on an IHC detection of ROS1 fusion proteins, confirmed if positive or doubtful by a ROS1 break-apart FISH assay, is pertinent in advanced "triple negative" lung adenocarcinomas, since the prevalence of ROS1-positive cases in this selected population reaches 7.4% in our series.
-
Lung cancer is an important health threat worldwide, and is associated with a 3.8-13.9% incidence of thrombophilia. Of interest, patients with lung tumors have been noted to have an increase in endogenous carbon monoxide production via upregulation of hemeoxygenase-1 activity. Given that it has been demonstrated that carbon monoxide enhances plasmatic coagulation in vitro and in vivo via formation of carboxyhemefibrinogen, we sought to determine if patients with thoracic tumors undergoing lung resection/pneumonectomy had an increase in endogenous carbon monoxide and concurrent plasmatic hypercoagulability. ⋯ Patients with thoracic tumors were determined to have an abnormally increased carboxyhemoglobin concentration of 2.1±0.6%, indicative of hemeoxygenase-1 upregulation. It was found that 84% of thoracic tumor patients had plasma clot strength that exceeded the 95% confidence interval value observed in normal subjects, and 44% of this hypercoagulable subgroup had carboxyhemefibrinogen formation. Future investigation of the role played by plasmatic hypercoagulability and hemeoxygenase-1 derived carboxyhemefibrinogen in the pathogenesis of thoracic tumor related thrombophilia is warranted.