An analysis of the results of this trial, which compared low-dose CT with chest radiography, showed that CT had a lower positive predictive value for a positive screening result but detected more ...lung cancers at earlier stages.
The National Lung Screening Trial (NLST) was a randomized trial of lung-cancer–specific mortality among participants in an asymptomatic high-risk cohort who underwent screening with the use of low-dose helical computed tomography (CT) as compared with screening with the use of single-view posteroanterior chest radiography. The NLST showed a 20% relative reduction in mortality from lung cancer with three rounds of low-dose CT screening (rounds T0, T1, and T2) as compared with radiography.
1
In this article, we present more detailed findings from the two incidence screenings (rounds T1 and T2), including information on rates of positive screening tests, performance characteristics of . . .
In this study involving nearly 77,000 men, investigators analyzed the effect of screening with prostate-specific–antigen testing and digital rectal examination on the rate of death from prostate ...cancer, as compared with usual care. After a follow-up of 7 years, the death rates from prostate cancer did not differ significantly between the two study groups. Data from the 10-year follow-up (which were 67% complete) also showed no significant difference in prostate-cancer mortality.
The benefit of screening for prostate cancer with serum prostate-specific–antigen (PSA) testing, digital rectal examination, or any other screening test is unknown. There has been no comprehensive assessment of the trade-offs between benefits and risks. Despite these uncertainties, PSA screening has been adopted by many patients and physicians in the United States and other countries. The use of PSA testing as a screening tool has increased dramatically in the United States since 1988.
1
Numerous observational studies have reported conflicting findings regarding the benefit of screening.
2
As a result, the screening recommendations of various organizations differ. The American Urological Association and . . .
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. INTERVENTION The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median range, 12.4 years 10.9-13.0 years) for cancer diagnoses and death until February 28, 2010. MAIN OUTCOME MEASURES Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. RESULTS Ovarian cancer was diagnosed in 212 women (5.7 per 10 000 person-years) in the intervention group and 176 (4.7 per 10 000 person-years) in the usual care group (rate ratio RR, 1.21; 95% confidence interval CI, 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10 000 person-years) in the intervention group and 100 deaths (2.6 per 10 000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10 000 person-years) in the intervention group and 2914 deaths (76.2 per 10 000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06). CONCLUSIONS Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00002540
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. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed. INTERVENTION Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009. MAIN OUTCOME MEASURES Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality. RESULTS Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10 000 person-years in the intervention group and 19.2 per 10 000 person-years in the usual care group (rate ratio RR; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10). CONCLUSION Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00002540
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.
Methods
A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results
Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P
interaction = .81), pretrial PSA testing (P
interaction = .52), and comorbidity (P
interaction = .68).
Conclusions
After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
Paul Pinsky of the US National Cancer Institute and colleagues describe the implementation and outcomes of web-based data sharing from the PLCO and NLST cancer screening trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The National Cancer Institute (NCI), in conjunction with
blinded university
, provides a mechanism to enable public access to the study data, CT radiology images, and pathology images from the ...National Lung Screening Trial (NLST). Access to the data and images is through the NCI-sponsored, blinded university-hosted The Cancer Imaging Archive (TCIA), a repository of more than 40 study collections of cancer images. Once access to the NLST data has been granted by NCI, a
Query Tool
within TCIA is used to access the NLST data and images. The Query Tool is a simple-to-use menu-driven database application designed to quickly pose queries and retrieve/save results (from 53,452 NLST participants), download CT images (~20 million available), and view pathology images (~1200 available). NLST study data are contained in 17 Query Tool tables with ~370 variables to query. This paper describes Query Tool design, functionality, and usefulness for researchers, clinicians, and software developers to query data, save query results, and download/view images.
A study was conducted to evaluate the efficacy of screening for lung cancer using modern chest radiographs on mortality from lung cancer. Results indicated that such form of screening was not ...effective in reducing mortality as compared to standard care.
Antigenic stimulation promotes T cell metabolic reprogramming to meet increased biosynthetic, bioenergetic, and signaling demands. We show that the one-carbon (1C) metabolism enzyme ...methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) regulates de novo purine synthesis and signaling in activated T cells to promote proliferation and inflammatory cytokine production. In pathogenic T helper-17 (Th17) cells, MTHFD2 prevented aberrant upregulation of the transcription factor FoxP3 along with inappropriate gain of suppressive capacity. MTHFD2 deficiency also promoted regulatory T (Treg) cell differentiation. Mechanistically, MTHFD2 inhibition led to depletion of purine pools, accumulation of purine biosynthetic intermediates, and decreased nutrient sensor mTORC1 signaling. MTHFD2 was also critical to regulate DNA and histone methylation in Th17 cells. Importantly, MTHFD2 deficiency reduced disease severity in multiple in vivo inflammatory disease models. MTHFD2 is thus a metabolic checkpoint to integrate purine metabolism with pathogenic effector cell signaling and is a potential therapeutic target within 1C metabolism pathways.
Display omitted
•MTHFD2 is critical for activated CD4 T cells to maintain de novo purine synthesis•Insufficient MTHFD2 promotes Treg cell-like phenotypes and metabolism in Th17 cells•Inhibition of MTHFD2 suppresses mTORC1 signaling and alters histone methylation•MTHFD2 can be targeted to protect against inflammation and autoimmunity in vivo
Nucleotide synthesis is required to support rapid T cell proliferation. Sugiura et al. show that de novo purine metabolism signals direct T cell differentiation and function and identify MTHFD2 as a metabolic checkpoint and therapeutic target for inflammatory diseases.
Effect of screening on ovarian cancer mortality Buys, Saundra S; Prorok, Philip C; Zhu, Claire S ...
JAMA : the journal of the American Medical Association,
06/2011, Letnik:
305, Številka:
22
Journal Article
Recenzirano
A study was conducted to evaluate the efficacy of screening for ovarian cancer on mortality caused by the same. Results indicated that such form of screening did not result in any reduction in ...mortality associated with ovarian cancer.
PDF
