Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: results from IALT, JBR.10 and ANITA.

Introduction: CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.

An evaluation of the possible interaction of gastric acid suppressing medication and the EGFR tyrosine kinase inhibitor erlotinib.

Objectives: As the bioavailability of erlotinib is dependent on gastric pH, an increase in gastric pH via the concurrent use of gastric acid suppressive medications (AS) may reduce its bioavailability and efficacy. We retrospectively analyzed the BR.21 trial database to pragmatically evaluate the impact of AS use on the median plasma drug levels of erlotinib, adverse events and outcome of participants.

Lung cancer in 2013: state of the art therapy for metastatic disease.

Lung cancer is the leading worldwide cause of cancer death and the majority of patients present with metastatic stage IV disease. At diagnosis, clinical, histologic, and molecular features must be considered in therapeutic decision-making for systemic therapy. Molecular testing for at least epidermal growth factor receptor (EGFR) and ALK should be performed in all patients before therapy.

Surrogate endpoints for overall survival in chemotherapy and radiotherapy trials in operable and locally advanced lung cancer: a re-analysis of meta-analyses of individual patients' data.

Background: The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful.

Pooled analysis of the prognostic and predictive effects of KRAS mutation status and KRAS mutation subtype in early-stage resected non-small-cell lung cancer in four trials of adjuvant chemotherapy.

Purpose: We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non-small-cell lung cancer (NSCLC).

Methods: KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model.

KRAS mutations as prognostic and predictive markers in non-small cell lung cancer.

A greater understanding of non-small-cell lung cancer at a molecular level has led to the identification of an increasing number of driver mutations. Extensive research of the KRAS gene as well as specific mutations has established its role in tumorigenesis. Nevertheless, the role of KRAS oncogene in non-small-cell lung cancer remains unclear.

ERCC1 isoform expression and DNA repair in non-small-cell lung cancer.

Background: The excision repair cross-complementation group 1 (ERCC1) protein is a potential prognostic biomarker of the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer (NSCLC). Although several ongoing trials are evaluating the level of expression of ERCC1, no consensus has been reached regarding a method for evaluation.

Methods: We used the 8F1 antibody to measure the level of expression of ERCC1 protein by means of immunohistochemical analysis in a validation set of samples obtained from 494 patients in two independent phase 3 trials (the National Cancer Institute of Canada Clinical Trials Group JBR.

Phase I-IIa study of BMS-690514, an EGFR, HER-2 and -4 and VEGFR-1 to -3 oral tyrosine kinase inhibitor, in patients with advanced or metastatic solid tumours.

Purpose: BMS-690514 is a potent, reversible oral inhibitor of epidermal growth factor receptor (EGFR/HER-1), HER-2 and -4, and vascular endothelial growth factor receptors (VEGFRs)-1 to -3 offering targeted inhibition of tumour growth and vascularisation in a single agent. This phase I-IIa study was designed to identify the maximum tolerated dose (MTD) and assess safety, antitumour activity, pharmacokinetics and pharmacodynamics of BMS-690514.

Patients And Methods: In phase I, patients with advanced solid tumours received escalating doses of once-daily BMS-690514.

Depression and use of health care services in patients with advanced cancer.

Objective: To examine whether depression in patients with advanced cancer is associated with increased rates of physician visits, especially to primary care.

Design: Retrospective, observational study linking depression survey data to provincial health administration data.

Setting: Toronto, Ont.

Factors associated with referral to medical oncology and subsequent use of adjuvant chemotherapy for non-small-cell lung cancer: a population-based study.

Background: Adjuvant chemotherapy (act) for non-small-cell lung cancer (nsclc) is associated with improved survival in the general population, but may be underutilized. We explored the factors associated with referral to medical oncology and subsequent use of act among all patients with resected nsclc in Ontario, Canada.

Methods: The Ontario Cancer Registry was used to identify all incident cases of nsclc diagnosed in Ontario during 2004-2006.

A phase I study of pomalidomide (CC-4047) in combination with cisplatin and etoposide in patients with extensive-stage small-cell lung cancer.

Introduction: This phase I/IIA study evaluated the maximum-tolerated dose (MTD), safety, and clinical benefit of pomalidomide, an immunomodulatory drug (IMiD), combined with cisplatin+etoposide chemotherapy, in treatment-naive patients with extensive-stage (ES) small-cell lung cancer (SCLC).

Methods: In this multicenter, open-label, dose-escalation study, patients received 21-day cycles of oral pomalidomide (1, 3, 5, and 4 mg/day) on days 1 to 14, plus cisplatin 25 mg/m and etoposide 100 mg/m administered intravenously on days 1 to 3; the MTD was determined during cycle 1 (standard 3+3 dose-escalation design), followed by a five-cycle extension phase.

Results: Twenty-two patients with ES SCLC, with a median age of 64.

Epidermal growth factor receptor inhibition in lung cancer: status 2012.

Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC).

Factors influencing a specific pathologic diagnosis of non-small-cell lung carcinoma.

Introduction: Historically, a non-small-cell lung carcinoma diagnosis, without pathologic subclassification, provided sufficient information to guide therapy. Evidence now demonstrates that pathologic subtype classification is central in selecting optimal treatment. This review aimed to identify factors associated with a specific pathologic diagnosis.

The communal coping model and cancer pain: the roles of catastrophizing and attachment style.

Unlabelled: Pain is among the most common symptoms of cancer, with impacts on multiple domains of well-being. Biopsychosocial factors play an important role in adjustment to cancer pain. The Communal Coping Model (CCM), which may elucidate the social context of cancer pain, suggests that people catastrophize to convey distress and elicit support.

Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer.

Background: We examined how crossover therapy might affect the association between progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC).

Methods: We extracted PFS- and OS-hazard ratios (HRs) in phase III trials of molecular-targeted agents for advanced NSCLC. Their relationship was modeled in a linear function with the coefficient of determination (R-squared) to assess the correlation between PFS and OS.

Exploiting the noise: improving biomarkers with ensembles of data analysis methodologies.

Background: The advent of personalized medicine requires robust, reproducible biomarkers that indicate which treatment will maximize therapeutic benefit while minimizing side effects and costs. Numerous molecular signatures have been developed over the past decade to fill this need, but their validation and up-take into clinical settings has been poor. Here, we investigate the technical reasons underlying reported failures in biomarker validation for non-small cell lung cancer (NSCLC).

Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study.

Background: The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non-small cell lung cancer (NSCLC).

Methods: All cases of NSCLC diagnosed in Ontario, Canada, from 2004 to 2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry.

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).

A phase I dose-escalation study of aflibercept administered in combination with pemetrexed and cisplatin in patients with advanced solid tumours.

Background: To evaluate the safety, pharmacokinetics (PKs), and pharmacodynamics of aflibercept, and to identify the recommended phase II dose (RP2D) of aflibercept in combination with pemetrexed and cisplatin.

Methods: Aflibercept was administered at escalating doses of 2, 4, or 6 mg kg(-1) in combination with fixed doses of pemetrexed (500 mg m(-2)) plus cisplatin (75 mg m(-2)) every 3 weeks. Blood samples were collected for PK analyses.

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.