Prognostic and predictive role of the VeriStrat plasma test in patients with advanced non-small-cell lung cancer treated with erlotinib or placebo in the NCIC Clinical Trials Group BR.21 trial.

Introduction: We investigated the predictive and prognostic effects of VeriStrat, a serum or plasma-based assay, on response and survival in a subset of patients enrolled on the NCIC Clinical Trials Group, BR.21 phase III trial of erlotinib versus placebo in previously treated advanced non-small-cell lung cancer patients.

Methods: Pretreatment plasma samples were available for 441 of 731 enrolled patients and were provided as anonymized aliquots to Biodesix.

Loss of phosphatase and tensin homolog protein expression is an independent poor prognostic marker in lung adenocarcinoma.

Introduction: Phosphatase and tensin homolog (PTEN) has been established as a tumor suppressor gene with an important role in regulating the phosphatidylinositol-3-kinase/AKT antiapoptotic and survival pathway. The prognostic role of PTEN in non-small-cell lung carcinoma has not been evaluated completely in the context of other molecular information.

Methods: Tissue microarrays containing 152 resected non-small-cell lung cancer specimens were used to investigate PTEN and p53 by immunohistochemistry and PTEN by fluorescence in situ hybridization.

Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial.

Purpose: To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant human fusion protein targeting the vascular endothelial growth factor (VEGF) pathway, with or without docetaxel in platinum-pretreated patients with advanced or metastatic nonsquamous non-small-cell lung cancer.

Patients And Methods: In this international, double-blind, placebo-controlled phase III trial, 913 patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n = 456) or IV placebo (n = 457), both administered every 3 weeks and in combination with docetaxel 75 mg/m(2). The primary end point was overall survival (OS).

Characterization of lymphomas developing in immunodeficient mice implanted with primary human non-small cell lung cancer.

Introduction: Xenograft models of epithelial malignancies potentially have greater correlation with clinical end points. We implanted 153 primary non-small cell lung carcinomas into non-obese diabetic-severe combined immunodeficient mice to develop primary lung cancer xenografts. Sixty-three xenografts formed.

A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer.

Introduction: The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status.

Association of the 15q25 and 5p15 lung cancer susceptibility regions with gene expression in lung tumor tissue.

Background: Genome-wide association studies have identified two independent lung cancer susceptibility loci at chromosome 15q25 and one locus at 5p15. We examined the association of genetic variants in these regions with gene expression in lung tumor tissue, in an effort to elucidate carcinogenic mechanisms by which these variants influence lung cancer risk.

Methods: We used data from 2 independent studies of non-small cell lung carcinoma patients: the JBR.

Adjuvant chemotherapy for non-small-cell lung cancer in the elderly: a population-based study in Ontario, Canada.

Purpose: Non-small-cell lung cancer (NSCLC) is predominantly a disease of the elderly. Retrospective analyses of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis suggest that the elderly benefit from adjuvant chemotherapy.

L1 cell adhesion molecule promotes tumorigenicity and metastatic potential in non-small cell lung cancer.

Purpose: Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells.

Adjuvant chemotherapy for non-small cell lung cancer: practice patterns and outcomes in the general population of Ontario, Canada.

Background: Adjuvant chemotherapy (ACT) is known to improve survival in patients with early-stage non-small cell lung cancer. Herein, we describe chemotherapy regimens used, dose modifications, survival, and treatment-related toxicity in the general population.

Methods: All cases of non-small cell lung cancer diagnosed in Ontario in the period 2004-2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry in this population-based retrospective cohort study.

Differential role of estrogen receptor beta in early versus metastatic non-small cell lung cancer.

Although women have an increased susceptibility to lung cancer, they also have a favorable clinical outcome. This may in part be due to female specific genetic and hormonal factors. In the present study, expression of ER-beta was investigated by immunohistochemistry using tissue samples from two cohorts: non-small cell lung cancer (NSCLC) diagnosed in 1999 in Manitoba and advanced NSCLC patients from the NCIC-CTG BR.

Locoregional failures following thoracic irradiation in patients with limited-stage small cell lung carcinoma.

Purpose: To determine the patterns of loco-regional (LR) and distant failure in patients with limited-stage small cell lung carcinoma (LS-SCLC) treated with curative intent.

Methods: From 1997 to 2008, 253 LS-SCLC patients were treated with curative intent chemo-radiation at our institution. A retrospective review identified sites of failure.

Optimized application of penalized regression methods to diverse genomic data.

Motivation: Penalized regression methods have been adopted widely for high-dimensional feature selection and prediction in many bioinformatic and biostatistical contexts. While their theoretical properties are well-understood, specific methodology for their optimal application to genomic data has not been determined.

Results: Through simulation of contrasting scenarios of correlated high-dimensional survival data, we compared the LASSO, Ridge and Elastic Net penalties for prediction and variable selection.

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.

Immunotherapy for non-small cell lung cancer: novel approaches to improve patient outcome.

Introduction: Non-small cell lung cancer (NSCLC) is often diagnosed in advanced stages and is associated with poor outcomes. Existing standards of care for NSCLC result in low overall cure rates, suggesting that novel treatment approaches are needed. In this review, we provide an updated look at the clinical data on immunotherapeutic interventions, which potentiate the immune system's response to lung tumor cells.

Clinical outcomes of extensive stage small cell lung carcinoma patients treated with consolidative thoracic radiotherapy.

Unlabelled: The purpose of this review was to determine the effect of consolidative thoracic radiotherapy (TRT) in patients with extensive stage small cell lung cancer (ES-SCLC) with minimal metastatic disease. Locoregional failure, distant failure and OS were 39%, 74% and 14% respectively at 2 years. No patients experienced clinical pneumonitis.

A systematic review and Canadian consensus recommendations on the use of biomarkers in the treatment of non-small cell lung cancer.

Introduction: Greater understanding of molecular pathways important in cell growth and proliferation of thoracic malignancies, particularly non-small cell lung cancer (NSCLC), has resulted in intense clinical and translational research. There is now considerable interest in personalizing treatment based on an understanding of tumor histology and molecular abnormalities. However, there is a multiplicity of data, often with discordant results resulting in confusion and uncertainty among clinicians.

Characteristics and outcomes of small cell lung cancer patients diagnosed during two lung cancer computed tomographic screening programs in heavy smokers.

Introduction: Small cell lung cancer (SCLC) is considered an inappropriate screening target due to its short preclinical phase and high rate of relapse despite optimal therapy. However, while intuitively screening for SCLC is inadvisable, in reality, there is a scarcity of data focusing on screen-detected SCLC and whether this intervention leads to diagnosis at an earlier clinical stage or alters outcome.

Methods: We conducted a retrospective review of the baseline characteristics, treatment, and outcome of SCLC patients diagnosed during two large-scale computed tomographic screening studies conducted in heavy smokers.

Non-small-cell lung cancer.

In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment.

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.

The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC.

Randomized phase II trial of concurrent versus sequential bortezomib plus docetaxel in advanced non-small-cell lung cancer: a California cancer consortium trial.

Background: The proteasome inhibitor bortezomib sensitizes tumor cells to chemotherapy-induced apoptosis. In preclinical non-small-cell lung cancer (NSCLC) models, p53-dependent growth arrest after bortezomib treatment resulted in reduced cytotoxicity if bortezomib preceded docetaxel. The reverse sequence of docetaxel before bortezomib was associated with increased apoptosis, cleavage of caspase-3 and PARP (poly [ADP-ribose] polymerase), and reduction in Bcl-2.

Treatment of the elderly when cure is the goal: the influence of age on treatment selection and efficacy for stage III non-small cell lung cancer.

Background: : Treatment of elderly patients with stage III NSCLC is controversial. Limited data exist, as the elderly are underrepresented in clinical trials.

Methods: : After ethics approval, we performed a retrospective review of 1372 stage III NSCLC patients treated at our institution during the period 1997-2007.

Pharmacogenetic and germline prognostic markers of lung cancer.

Introduction: Lung cancer is the leading global cause of cancer-related mortality. Interindividual variability in treatment response and cancer outcomes has focused attention on genetic polymorphisms as prognostic markers. We evaluated the overall contribution of candidate polymorphism association studies to our current understanding of the genetic predictors of lung cancer outcomes.