Overall and Multiphasic Findings of the Prostate, Lung, Colorectal and Ovarian (PLCO) Randomized Cancer Screening Trial.

Background: Screening tests are typically evaluated for a single disease, but multiple tests for multiple diseases are performed in practice. The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial assessed testing for four cancers simultaneously and can be viewed as a multiphasic cancer intervention. This paper presents overall and multiphasic findings of this trial.

Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years.

Background: Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial.

Extended mortality results for ovarian cancer screening in the PLCO trial with median 15years follow-up.

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial originally reported no mortality benefit of ovarian cancer screening after a median of 12.4years of follow-up. The UKCTOCS screening trial failed to show a statistically significant mortality reduction in the primary analysis but reported an apparent increased mortality benefit in trial years 7-14 compared to 0-7.

Managing Multi-Center Recruitment in the PLCO Cancer Screening Trial.

There were significant recruitment challenges specific to the PLCO Cancer Screening Trial. Large numbers of participants were to be randomized from ten catchment areas nationwide within time and budgetary constraints. The eligible population was elderly and had to meet health and behavioral thresholds.

Building Successful Relationships in the PLCO Cancer Screening Trial.

Biomedical research cannot succeed without funding, knowledgeable staff, and appropriate infrastructure. There are however equally important but intangible factors that are rarely considered in planning large multidisciplinary endeavors or evaluating their success. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial required extensive collaborations between individuals from many fields, including clinicians, clinical trialists, and administrators; it also addressed questions across the spectrum of cancer prevention and control.

Changes in and Impact of the Death Review Process in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Death review was conducted for the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial to avoid the biases associated with causes of death entered on death certificates. An algorithm selected deaths for review. Records on diagnosis and terminal illness were perused in the coordinating center and by the chair of the death review committee (DRC).

Comprehensive Quality Management (CQM) in the PLCO Trial.

The NCI imbedded the notion of comprehensive quality control and assurance (CQA) in the design concept for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. PLCO implemented a comprehensive, adaptable quality assurance and control program to span more than 20 years of data collection, coordinate multiple institutions and committees, and integrate a wide variety of complex protocols. CQA concepts, practices, and procedures traced through all aspects of trial management, governance, and operations of PLCO.

The PLCO Biorepository: Creating, Maintaining, and Administering a Unique Biospecimen Resource.

Inclusion of biospecimens in population-based studies is an integral part of understanding disease etiology, identifying biomarkers and developing prevention and treatment strategies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial collected, processed and stored biospecimens from participants to create a biorepository of specimens which serves as a useful resource for a broad research community. PLCO collected blood samples from consented screening arm participants at six screening rounds and a buccal sample from consented control arm participants.

The PLCO Cancer Screening Trial: Background, Goals, Organization, Operations, Results.

The randomized PLCO trial was designed to answer four primary questions: does screening for these cancers using often promoted tests reduce cancer-specific mortality? Nearly 155,000 men and women were allocated to screening or usual care arms in a 1:1 ratio under a centralized, secure randomization algorithm at ten competitively selected screening centers nationwide. Screened men received PSA blood tests and digital rectal examinations. Screened women received CA125 blood tests and trans-vaginal ultrasound.

Multilevel modeling and value of information in clinical trial decision support.

Background: Clinical trials are the main method for evaluating safety and efficacy of medical interventions and have produced many advances in improving human health. The Women's Health Initiative overturned a half-century of harmful practice in hormone therapy, the National Lung Screening Trial identified the first successful lung cancer screening tool and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial overturned decades-long assumptions. While some trials identify unforeseen safety issues or harms, many fail to demonstrate efficacy.

The prostate, lung, colorectal, and ovarian cancer screening trial and its associated research resource.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource.

Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism.

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions.

Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy.

Background: The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality.

Methods: From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care.

Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up.

Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.

Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial.

Context: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown.

Objective: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Design, Setting, And Participants: Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001.

Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial.

Context: Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality.

Objective: To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Design, Setting, And Participants: Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001.

The National Lung Screening Trial: overview and study design.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase.

Lung cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Background: The 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates.

Cumulative incidence of false-positive results in repeated, multimodal cancer screening.

Purpose: Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program.

Methods: Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality.

Mortality results from a randomized prostate-cancer screening trial.

Background: The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality.

Methods: From 1993 through 2001, we randomly assigned 76,693 men at 10 U.

Potential of computer-aided diagnosis to improve CT lung cancer screening.

The development of low-dose spiral computed tomography (CT) has rekindled hope that effective lung cancer screening might yet be found. Screening is justified when there is evidence that it will extend lives at reasonable cost and acceptable levels of risk. A screening test should detect all extant cancers while avoiding unnecessary workups.

Prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial.

Objective: To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality.

Subjects And Methods: In all, 38 349 men aged 55-74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE.

A review of imaging techniques for systems biology.

This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), and molecular probes such as quantum dots and nanoshells in systems biology.

Enrollment of racial and ethnic minorities in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Background: Minority populations in the United States, especially blacks and Hispanics, are generally underrepresented among participants in clinical trials. Here, we report the experience of enrolling ethnic minorities in a large cancer screening trial.

Methods: The Prostate, Colorectal, Lung and Ovarian (PLCO) Cancer Screening Trial is a multicenter randomized trial designed to evaluate the effectiveness of screening for the PLCO cancers.