BACKGROUND
The National Lung Screening Trial (NLST), which compared lung cancer screening with low‐dose computed tomography (LDCT) versus chest radiography (CXR), demonstrated a statistically ...significant mortality benefit of LDCT screening. In the current study, the authors performed a post hoc analysis to examine whether the benefit was affected by various baseline factors, including age, sex, and smoking status, and whether it differed by tumor histology.
METHODS
Lung cancer death rates were computed as events over person‐years of observation; the mortality risk ratio (RR) was defined as the lung cancer death rate in the LDCT versus CXR trial arms. Poisson regression was used to test for interactions of sex, age (< 65 years vs ≥ 65 years), and smoking status (current vs former) with trial arm. Mortality RRs were also computed for specific lung cancer histologies.
RESULTS
The overall mortality RR was 0.92 in men and 0.73 in women, with a P value for interaction of .08. RRs were similar for individuals aged < 65 years versus those aged ≥ 65 years (0.82 vs 0.87), and for current versus former smokers (0.81 vs 0.91). By tumor histology, mortality RRs were 0.75 for adenocarcinoma, 0.71 for all non‐small cell lung cancers except squamous, 1.23 for squamous cell carcinoma, and 0.90 for small cell carcinoma. RRs were similar for men and women for nonsquamous non‐small cell lung cancers (0.71 and 0.70, respectively); women were found to have lower RRs for small cell and squamous cell carcinoma.
CONCLUSIONS
A benefit of LDCT did not appear to vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist. Cancer 2013;119:3976–3983. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
The benefit of computed tomography screening in the National Lung Screening Trial did not vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist.
After nearly 12 years of follow-up, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial has shown that screening with flexible sigmoidoscopy reduces colorectal-cancer incidence by 21% ...and mortality by 26%.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States.
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Colorectal-cancer mortality
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–
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and incidence
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,
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are reduced with screening by means of fecal occult-blood testing. Endoscopic screening with flexible sigmoidoscopy or colonoscopy is more sensitive than fecal testing for the detection of adenomatous polyps, the precursor lesions of colorectal cancer.
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Three European randomized trials of flexible sigmoidoscopy have been performed.
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In the United Kingdom, one-time screening with flexible sigmoidoscopy significantly reduced the incidence of colorectal cancer (by 23%) and associated mortality (by 31%).
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In Italy, an 18% reduction in incidence and a nonsignificant 22% . . .
Estimates of prostate cancer-specific mortality (PCSM) were similar for men randomly assigned to intervention compared with usual care on the Prostate, Lung, Colorectal and Ovarian PC screening ...study. However, results analyzed by comorbidity strata remain unknown.
Between 1993 and 2001, of 76,693 men who were randomly assigned to usual care or intervention at 10 US centers, 73,378 (96%) completed a questionnaire that inquired about comorbidity and prostate-specific antigen (PSA) testing before random assignment. Fine and Gray's multivariable analysis was performed to assess whether the randomized screening arm was associated with the risk of PCSM in men with no or minimal versus at least one significant comorbidity, adjusting for age and prerandomization PSA testing.
After 10 years of follow-up, 9,565 deaths occurred, 164 from PC. A significant decrease in the risk of PCSM (22 v 38 deaths; adjusted hazard ratio AHR, 0.56; 95% CI, 0.33 to 0.95; P = .03) was observed in men with no or minimal comorbidity randomly assigned to intervention versus usual care, and the additional number needed to treat to prevent one PC death at 10 years was five. Among men with at least one significant comorbidity, those randomly assigned to intervention versus usual care did not have a decreased risk of PCSM (62 v 42 deaths; AHR, 1.43; 95% CI, 0.96 to 2.11; P = .08).
Selective use of PSA screening for men in good health appears to reduce the risk of PCSM with minimal overtreatment.
In reply to Krabbe et al Izmirlian, Grant, Ph.D; Paciorek, Jon
Urologic oncology,
2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
33, Številka:
1
Journal Article
Studies examining career satisfaction of biomedical scientists are limited, especially in the context of prior postdoctoral training. Here we focused on career satisfaction defined as satisfaction ...with one's career trajectory and perceived salary competitiveness among a predominantly Ph.D.-trained population of scientists who completed cancer prevention-related postdoctoral training between 1987-2011. National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP) alumni (n = 114), and previous recipients of NCI-sponsored Ruth L. Kirschstein National Research Service Award (NRSA/F32) postdoctoral fellowships (n = 140) completed online surveys. Associations of career satisfaction and perception of salary competitiveness with demographic, training, and employment-related factors were examined using logistic regression. Overall, 61% reported high levels of satisfaction with their career trajectory to-date. Higher salary (odds ratio OR = 2.86, 95% confidence interval 95% CI: 1.07-7.69) and having more leadership roles (OR = 2.26, 95% CI:1.04-4.90) were independently associated with higher career satisfaction. Persons with race/ethnicity other than white (OR = 0.40, 95% CI: 0.20-0.82) or age ≥ 50 (OR = 0.40, 95%CI: 0.17-0.94) had lower career satisfaction levels. There were no statistically significant differences in career satisfaction levels by gender, scientific discipline, or employment sector. 74% perceived their current salary as competitive, but persons with 5-9, or ≥10 years in their current position reported lower levels (OR = 0.31, 95% CI: 0.15-0.65; and OR = 0.37, 95% CI: 0.16-0.87, respectively), as did individuals in government positions (OR = 0.33, 95% CI: 0.11-0.98). These data add to the understanding of career satisfaction of those with advanced training in biomedical research by examining these measures in relation to prior postdoctoral research training and across multiple career sectors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Benjamini–Hochberg (BH) false discovery rate (FDR) procedure enjoys widespread use in multiple testing scenarios when the cost of false positives is low and the number of simultaneous tests ...prohibits use of the Bonferroni procedure. The FDR and the average power are each expected values, of the false discovery proportion (FDP) and true positive proportion (TPP), respectively. Chi (2007), proved a law of the iterated logarithm (LIL) for the positive proportion (PP), FDP and TPP, and discusses a criticality phenomenon whereby a minimal FDR corresponding to the effect size is required for a nonzero rate of positive calls. While almost sure convergence follows as a corollary, no direct simple proof exists in the literature. We provide this result under the same set of conditions. Of greater consequence, we prove central limit results (CLT) for the PP, FPF and TPP under these weak conditions, providing full characterization of the limits.
Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial.
This was a randomized controlled trial of screening ...versus usual care. Baseline screening results are reported.
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.
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.
Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and
body mass index (BMI). It has been recently proposed that this relationship ...may be explained by the larger plasma volume of
obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in
the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening,
28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline.
Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration
times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration,
plasma volume, PSA mass, and BMI.
Results: PSA concentration significantly decreased with increasing BMI ( P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese
(BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and
PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories
( P = 0.10).
Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained
by a hemodilution effect. These findings could have implications for prostate cancer screening in large men. (Cancer Epidemiol
Biomarkers Prev 2009;18(3):748–51)
The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP), a structured in-house postdoctoral training ...program of 3-4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987-2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher's exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio OR = 4.99, 95% confidence interval 95% CI): 1.91-13.0) were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38-13.2). In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
: 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.
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