The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un).

Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.

Background: Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer.

Introduction: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.

Methods: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification.

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the N Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma.

Introduction: Nodal categories for malignant pleural mesothelioma are derived from the lung cancer staging system and have not been adequately validated. The International Association for the Study of Lung Cancer developed a multinational database to generate evidence-based recommendations to inform the eighth edition of the TNM classification of malignant pleural mesothelioma.

Methods: Data from 29 centers were entered prospectively (n = 1566) or by transfer of retrospective data (n = 1953).

The IASLC Mesothelioma Staging Project: Proposals for Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Pleural Mesothelioma.

Introduction: The current T component for malignant pleural mesothelioma (MPM) has been predominantly informed by surgical data sets and consensus. The International Association for the Study of Lung Cancer undertook revision of the seventh edition of the staging system for MPM with the goal of developing recommendations for the eighth edition.

Methods: Data elements including detailed T descriptors were developed by consensus.

The IASLC Mesothelioma Staging Project: Proposals for the M Descriptors and for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Mesothelioma.

Introduction: The M component and TNM stage groupings for malignant pleural mesothelioma (MPM) have been empirical. The International Association for the Study of Lung Cancer developed a multinational database to propose evidence-based revisions for the eighth edition of the TNM classification of MPM.

Methods: Data from 29 centers were submitted either electronically or by transfer of existing institutional databases.

The IASLC Lung Cancer Staging Project: Methodology and Validation Used in the Development of Proposals for Revision of the Stage Classification of NSCLC in the Forthcoming (Eighth) Edition of the TNM Classification of Lung Cancer.

Introduction: Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017.

Methods: An international database of 94,708 patients with lung cancer diagnosed in 1999-2010 was assembled.

PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.

Background: Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.

Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C.

Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks.

A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection.

Background & Aims: Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events.

Methods: This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks.

Modafinil for the treatment of cocaine dependence.

Aim: Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.

Methods: This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study.

Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Objectives: Losses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making.

Functional status in rate- versus rhythm-control strategies for atrial fibrillation: results of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Functional Status Substudy.

Objectives: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) functional status substudy aimed to test the hypothesis that functional status is similar in rate-control and rhythm-control strategies.

Background: Randomized studies, including the AFFIRM study, have failed to demonstrate survival benefits between rate-control and rhythm-control strategies for atrial fibrillation (AF). However, AF may cause functional capacity or cognitive impairment that might justify maintenance of sinus rhythm.

Clinical factors that influence response to treatment strategies in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Background: The AFFIRM Study was a randomized multicenter comparison of 2 treatment strategies, rate-control versus rhythm-control, in high-risk patients with atrial fibrillation (AF). The primary outcome of the trial showed no overall difference in survival between strategies. However, there may be important patient subgroups for which there are identifiable differences in outcome with 1 of the 2 strategies.

Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in AFFIRM.

Objectives: We investigated whether inhibition of endogenous angiotensin II signaling reduces the recurrence rate of atrial fibrillation (AF) in patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Background: Structural and electrical remodeling contribute to AF. Previous experimental studies have implicated the angiotensin II signaling pathway in this process, and recent clinical evidence supports a beneficial effect of inhibiting angiotensin II activity.

Alternative endpoints for mortality in studies of patients with atrial fibrillation: the AFFIRM study experience.

Objectives: The purpose of this study was to examine possible alternatives for death, particularly hospitalization for cardiovascular reasons (CV hospitalization), as an endpoint in studies of atrial fibrillation (AF) using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) database.

Background: AF is associated with increased mortality, but large numbers of patients are needed to demonstrate even a moderate effect of a therapy on mortality.

Methods: AFFIRM studied 4,060 patients with AF, randomized to either rate-control or rhythm-control strategy with death as the primary endpoint.

Quality of life in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

Objective: The objective of this prespecified substudy of the AFFIRM study, in which no differences in survival or event rates were found in patients with atrial fibrillation (AF) randomized to either rate control or rhythm control, was to test the null hypothesis that quality of life (QoL) is equal with rate- versus rhythm-control treatment strategies in AF.

Methods: Fifty-six (25%) of AFFIRM sites were randomly selected to recruit AFFIRM patients for the QoL substudy. Instruments used in the QoL assessment were (1) Perceived Health; (2) the Cantril Ladder of Life; (3) the Short Form 36 survey; (4) the QoL Index; and (5) the Symptom Checklist: Frequency and Severity.

Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study.

Background: The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time.

Methods And Results: Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables.

Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.

Background: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.

Objective: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.

Design: Population-based longitudinal study of coronary heart disease and stroke.

A regression model for longitudinal change in the presence of measurement error.

Purpose: The analysis of change in measured variables has become quite popular in studies where data are collected repeatedly over time. The authors describe some of the potential pitfalls in the analysis of change when the variable for change is measured with error. They show that regression analysis is often biased, possibly leading to erroneous results.