Response to 'Receiver operating characteristics of the prostate-specific antigen test in an unselected population'.
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Age Factors↗
Biomedical subjects
Grant Izmirlian
Publications and source records attributed to Grant Izmirlian.
Prostate Cancer Screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: findings from the initial screening round of a randomized trial.
BACKGROUND: The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. METHODS: A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. RESULTS: Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. CONCLUSION: The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.
Aged↗
Modeling the dissemination of mammography in the United States.
OBJECTIVE: This paper presents a methodology for piecing together disparate data sources to obtain a comprehensive model for the use of mammography screening in the US population for the years 1975-2000. METHODS: Two aspects of mammography usage, the age that a woman receives her first mammography and the interval between subsequent mammograms, are modeled separately. The initial dissemination of mammography is based on cross-sectional self report data from national surveys and the interval length between screening exams is fit using longitudinal mammography registry data. RESULTS: The two aspects of mammography usage are combined to simulate screening histories for individual women that are representative of the US population. Simulated mammography patterns for the years 1994-2000 were found to be similar to observed screening patterns from the state level mammography registry for Vermont. CONCLUSIONS: The model presented gives insight into screening practices over time and provides an alternative public health measure for screening usage in the US population. The comprehensive description of mammography use from its introduction represents an important first step to understanding the impact of mammography on breast cancer incidence and mortality.
Age Distribution↗
Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial.
OBJECTIVE: Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial. STUDY DESIGN: This was a randomized controlled trial of screening versus usual care. Baseline screening results are reported. RESULTS: Of 39,115 women randomized to receive screening, 28,816 received at least 1 test. Abnormal TVU was found in 1338 (4.7%), and abnormal CA-125 in 402 (1.4%). Twenty-nine neoplasms were identified (26 ovarian, 2 fallopian, and 1 primary peritoneal neoplasm). Nine were tumors of low malignant potential and 20 were invasive. The positive predictive value for invasive cancer was 3.7% for an abnormal CA-125, 1.0% for an abnormal TVU, and 23.5% if both tests were abnormal. CONCLUSION: The effect of screening on ovarian cancer mortality in the PLCO cohort has yet to be evaluated and will require longer follow-up. Screening identified both early- and late-stage neoplasms, and the predictive value of both tests was relatively low.
Aged↗
Serum proteomic profiles suggest celecoxib-modulated targets and response predictors.
Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer prevention clinical trial on patients with the inherited autosomal dominant condition, familial adenomatous polyposis, celecoxib proved efficacious. However, a remarkable heterogeneity in patients' responses to the chemopreventive effects of celecoxib was observed. Proteomic profiling of sera from these patients identified several markers, the expression of which was specifically modulated after treatment with celecoxib. A decision tree algorithm identified classifiers for response to celecoxib with relatively high sensitivity but moderate to low specificity. In particular, a spectral feature at m/z 16,961.4 was identified as a strong discriminator between response and nonresponse to celecoxib at the highest dose.
Adenomatous Polyposis Coli↗
Overview of commonly used bioinformatics methods and their applications.
Bioinformatics, in its broad sense, involves application of computer processes to solve biological problems. A wide range of computational tools are needed to effectively and efficiently process large amounts of data being generated as a result of recent technological innovations in biology and medicine. A number of computational tools have been developed or adapted to deal with the experimental riches of complex and multivariate data and transition from data collection to information or knowledge. These include a wide variety of clustering and classification algorithms, including self-organized maps (SOM), artificial neural networks (ANN), support vector machines (SVM), fuzzy logic, and even hyphenated techniques as neuro-fuzzy networks. These bioinformatics tools are being evaluated and applied in various medical areas including early detection, risk assessment, classification, and prognosis of cancer. The goal of these efforts is to develop and identify bioinformatics methods with optimal sensitivity, specificity, and predictive capabilities.
Computational Biology↗
Application of the random forest classification algorithm to a SELDI-TOF proteomics study in the setting of a cancer prevention trial.
A thorough discussion of the random forest (RF) algorithm as it relates to a SELDI-TOF proteomics study is presented, with special emphasis on its application for cancer prevention: specifically, what makes it an efficient, yet reliable classifier, and what makes it optimal among the many available approaches. The main body of the paper treats the particulars of how to successfully apply the RF algorithm in a proteomics profiling study to construct a classifier and discover peak intensities most likely responsible for the separation between the classes.
Algorithms↗
Comparative effects of DHEA and DHT on gene expression in human LNCaP prostate cancer cells.
BACKGROUND: DHEA is widely used as a dietary supplement in older men. Because DHEA can be converted to androgens or estrogens, such use may promote prostate cancer. In this study, the effects of DHEA were compared with those of DHT using gene expression array profiles in human LNCaP prostate cancer cells. MATERIALS AND METHODS: LNCaP cells were exposed to DHEA (300 nM), DHT (300 nM), or vehicle for 48 h, and mRNA expression was measured using Affymetrix HU-95 gene chips. Gene expression values were sorted in ascending order on the p-values corresponding to the extent of differential RNA expression between control and either hormone treatment. RESULTS: S100 calcium binding protein, neurotensin, 24-dehydrocholesterol reductase, and anterior-gradient 2 homologue were the four most differentially expressed genes (p-values all < 3 x 10(-5)). Nested tests of differential expression revealed lesser effects of DHEA versus DHT treatment (p < 0.01) for the S100 calcium binding protein and neurotensin genes. Microarray findings were confirmed by QRT-PCR. The top 83 genes exhibiting differential expression after DHEA or DHT were used for pathway analysis. DHT decreased expression of more genes involved in intercellular communication, signal transduction, nucleic acid binding and transport, and in structural components, such as myosin and golgin, than DHEA. CONCLUSION: These data revealed consistent, measurable changes in gene expression patterns following treatment of LNCaP prostate cancer cells with DHEA and DHT. Understanding the mechanisms of DHEA versus DHT actions in the prostate may help clarify the separate and interactive effects of androgenic and estrogenic actions in prostate cancer progression.
Adjuvants, Immunologic↗