Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis.
...To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in a subgroup of the National Lung Screening Trial (NLST).
In an NLST subgroup (n = 18,714), screening participants were randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n = 9,357) screening and monitored for a mean of 6.1 years. After baseline prebronchodilator spirometry, to identify the presence of airflow limitation, 18,475 subjects (99%) were assigned as having chronic obstructive pulmonary disease (COPD) or no COPD. Lung cancer prevalence, incidence, histology, and stage shift were compared after stratification by COPD.
For screening participants with spirometric COPD (n = 6,436), there was a twofold increase in lung cancer incidence (incident rate ratio, 2.15; P < 0.001) and, when compared according to screening arm, no excess lung cancers and comparable histology. Compared with chest radiography, there was also a trend favoring reduced late-stage and increased early-stage cancers in the CT arm (P = 0.054). For those with normal baseline spirometry (n = 12,039), we found an excess of lung cancers during screening in the CT arm, almost exclusively early-stage adenocarcinoma-related cancers (histology shift and overdiagnosis). After correction for these excess cancers, stage shift was marginal (P = 0.077).
In the CT arm of the NLST-ACRIN (American College of Radiology Imaging Network) cohort, COPD status was associated with a doubling of lung cancer incidence, no apparent overdiagnosis, and a more favorable stage shift.
Summary Background Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This ...study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. Methods We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55–74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov , number NCT00047385. Findings Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 95% CI 337·97–408·26 per 100 000 person-years vs 661·23 622·07–702·21) and had lower lung cancer-related mortality (185·82 95% CI 162·17–211·93 per 100 000 person-years vs 277·20 252·28–303·90). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 95% CI 162·17–211·93 per 100 000 person-years to 212·14 186·80–239·96) over the course of the trial. Interpretation Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. Funding None.
Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear ...relationship between the severity of airflow limitation and lung cancer risk.
We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4.
In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group).
Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less.
In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.
The disability associated with depression and its impact on maternal and child health has important implications for public health policy. While the prevalence of postnatal depression is high, there ...are no prevalence data on antenatal depression in South Africa. The purpose of this study was to determine the prevalence and correlates of depressed mood in pregnancy in Cape Town peri-urban settlements.
This study reports on baseline data collected from the Philani Mentor Mothers Project (PMMP), a community-based, cluster-randomized controlled trial on the outskirts of Cape Town, South Africa. The PMMP aims to evaluate the effectiveness of a home-based intervention for preventing and managing illnesses related to HIV, TB, alcohol use and malnutrition in pregnant mothers and their infants. Participants were 1062 pregnant women from Khayelitsha and Mfuleni, Cape Town. Measures included the Edinburgh Postnatal Depression Scale (EPDS), the Derived AUDIT-C, indices for social support with regards to partner and parents, and questions concerning socio-demographics, intimate partner violence, and the current pregnancy. Data were analysed using bivariate analyses followed by logistic regression.
Depressed mood in pregnancy was reported by 39% of mothers. The strongest predictors of depressed mood were lack of partner support, intimate partner violence, having a household income below R2000 per month, and younger age.
The high prevalence of depressed mood in pregnancy necessitates early screening and intervention in primary health care and antenatal settings for depression. The effectiveness and scalability of community-based interventions for maternal depression must be developed for pregnant women in peri-urban settlements.
ClinicalTrials.gov: NCT00972699.
Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a ...paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner.
Mentor Mothers were trained to conduct home visits. Mentor Mothers went from house to house in assigned neighborhoods, weighed children age 5 and younger, and recruited mother-child dyads where there was an underweight child. Participating dyads were assigned in a 2:1 random sequence to the Philani intervention condition (n = 536) or a control condition (n = 252). Mentor Mothers visited dyads in the intervention condition for one year, supporting mothers' problem-solving around nutrition. All children were weighed by Mentor Mothers at baseline and three, six, nine and twelve month follow-ups.
By three months, children in the intervention condition were five times more likely to rehabilitate (reach a healthy weight for their ages) than children in the control condition. Throughout the course of the study, 43% (n = 233 of 536) of children in the intervention condition were rehabilitated while 31% (n = 78 of 252) of children in the control condition were rehabilitated.
Paraprofessional Mentor Mothers are an effective strategy for delivering home visiting programs by providing the knowledge and support necessary to change the behavior of families at risk.
Study objective Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with ...low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial. Methods Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use. Results One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI –5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference –2.1%; 95% CI –7.9% to 3.7%), hospital admissions (16% versus 17%; difference –0.9%; 95% CI –6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference –0.4%; 95% CI –6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%). Conclusion A coronary CT angiography–based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing.
A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) ...with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.
Abstract Background Human immunodeficiency virus (HIV)-infected individuals are at increased risk for primary lung cancer (LC). We wished to compare the clinicopathologic features and treatment ...outcome of HIV-LC patients with HIV-indeterminate LC patients. We also sought to compare behavioral characteristics and immunologic features of HIV-LC patients with HIV-positive patients without LC. Patients and Methods A database of 75 HIV-positive patients with primary LC in the HAART era was established from an international collaboration. These cases were drawn from the archives of contributing physicians who subspecialize in HIV malignancies. Patient characteristics were compared with registry data from the Surveillance Epidemiology and End Results program (SEER; n = 169,091 participants) and with HIV-positive individuals without LC from the Adult and Adolescent Spectrum of HIV-related Diseases project (ASD; n = 36,569 participants). Results The median age at HIV-related LC diagnosis was 50 years compared with 68 years for SEER participants ( P < .001). HIV-LC patients, like their SEER counterparts, most frequently presented with stage IIIB/IV cancers (77% vs. 70%), usually with adenocarcinoma (46% vs. 47%) or squamous carcinoma (35% vs. 25%) histologies. HIV-LC patients and ASD participants had comparable median nadir CD4+ cell counts (138 cells/μL vs. 160 cells/μL). At LC diagnosis, their median CD4+ count was 340 cells/μL and 86% were receiving HAART. Sixty-three HIV-LC patients (84%) received cancer-specific treatments, but chemotherapy-associated toxicity was substantial. The median survival for both HIV-LC patients and SEER participants with stage IIIB/IV was 9 months. Conclusion Most HIV-positive patients were receiving HAART and had substantial improvement in CD4+ cell count at time of LC diagnosis. They were able to receive LC treatments; their tumor types and overall survival were similar to SEER LC participants. However, HIV-LC patients were diagnosed with LC at a younger age than their HIV-indeterminate counterparts. Future research should explore how screening, diagnostic and treatment strategies directed toward the general population may apply to HIV-positive patients at risk for LC.
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