Sally Freels

Brain tumor survival: Results from the National Cancer Data Base

Hospital-based data reported to the National Cancer Data Base (NCDB) were available for over 60,000 patients with a primary brain tumor diagnosed from 1985–1988 and 1990–1992. The most common histologies were glioblastomas, astrocytomas and meningiomas. Five-year survival rates for these tumors were 2%, 30% and 70% respectively. Histology, age at diagnosis, behavior, and location were important variables in estimating survival. Comparisons with population-based registry data suggest that the malignant tumors are well represented in NCDB, but the benign histologies are under-reported. Survival estimates for the malignant tumors are comparable to previously reported studies. The NCDB provides recent information on brain tumor distribution and survival patterns not available in other large databases.

Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology

Prevalence is the best indicator of cancer survivorship in the population, but few studies have focused on brain tumor prevalence because of previous data limitations. Hence, the full impact of primary brain tumors on the healthcare system in the United States is not completely described. The present study provides an estimate of the prevalence of disease in the United States, updating an earlier prevalence study. Incidence data for 2004 and survival data for 1985-2005 were obtained by the Central Brain Tumor Registry of the United States from selected regions, modeled under 2 different survival assumptions, to estimate prevalence rates for the year 2004 and projected estimates for 2010. The overall incidence rate for primary brain tumors was 18.1 per 100 000 person-years with 2-, 5-, 10-, and 20-year observed survival rates of 62%, 54%, 45%, and 30%, respectively. On the basis of the sum of nonmalignant and averaged malignant estimates, the overall prevalence rate of individuals with a brain tumor was estimated to be 209.0 per 100 000 in 2004 and 221.8 per 100 000 in 2010. The female prevalence rate (264.8 per 100 000) was higher than that in males (158.7 per 100 000). The averaged prevalence rate for malignant tumors (42.5 per 100 000) was lower than the prevalence for nonmalignant tumors (166.5 per 100 000). This study provides estimates of the 2004 (n = 612 770) and 2010 (n = 688 096) expected number of individuals living with primary brain tumor diagnoses in the United States, providing more current and robust estimates for aiding healthcare planning and patient advocacy for an aging US population.

The relation of age, race, and gender to the subsite location of colorectal carcinoma

Characteristics that determine the anatomic site within the colorectum where carcinoma is most likely to occur would be useful in choosing optimal modalities for cancer screening and in the study of etiology. The aim of this study was to identify any association of gender, race, or age with colorectal carcinoma in the proximal or distal colorectum.

Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups

Prevalence rates are used to supplement descriptions of disease and are unavailable for all primary brain tumors in the United States. Data from two population-based tumor registries were obtained from the Central Brain Tumor Registry of the United States and used to compute age-specific incidence rates (1985-1994) and survival curves for further use in a statistical model to estimate prevalence rates. Prevalence rates were then used to estimate the number of individuals living with a brain tumor diagnosis in the U.S. population for the year 2000. The overall incidence rate in these regions is 13.8 per 100,000 with 2-, 5-, and 10-year survival rates of 58%, 49%, and 38%, respectively. The prevalence rate for all primary brain tumors is 130.8 per 100,000 with approximately 350,000 individuals estimated to be living with this diagnosis in the United States in 2000. The prevalence rate for malignant tumors, 29.5 per 100,000, is similar to previous reports. The prevalence rate for benign tumors, 97.5 per 100,000, is new. Unlike incidence data, the proportion (and expected number) of existing benign tumors (75%, 267,000) is considerably greater than that for malignant tumors (23%, 81,000), reflecting the better prognosis of benign tumors diagnosed in individuals younger than 60 years old. These data underscore the impact of primary brain tumors in the U.S. health care system and emphasize the need for quality-of-life considerations, particularly for those long-term survivors of benign tumors.

The conditional probability of survival of patients with primary malignant brain tumors: surveillance, epidemiology, and end results (SEER) data.

Five‐year survival estimates in standard cancer reports provide a general description of disease outcome that is useful for surveillance and comparison purposes. However, for cancer survivors these overall survival rates may be discouraging, and the relevant question regarding an individual is this: Once he or she has survived for a specified period of time, what is the probability of survival over the next period of time?

Trends in incidence of primary brain tumors in the United States,1985-1994

Brain tumor incidence has increased over the last 20 years in all age groups, both overall and for specific histologies. Reasons attributed to these increases include increase in lymphoma due to HIV/AIDS, introduction of computed tomography/magnetic resonance imaging, and changes in coding/classification. The purpose of this study was to describe overall and histologic-specific incidence trends in a population-based series of primary benign and malignant brain tumors. Data from the Central Brain Tumor Registry of the United States from 1985 through 1994 were used to determine incidence trends in the broad age groups 0-19, 20-64, and > or = 65 years, both overall and for selected histologies. Poisson regression was used to express trends as average annual percentage change. Overall, incidence increased modestly (annual percentage change 0.9%, 95% confidence interval, 0.4, 1.4). When lymphomas were excluded, this result was not statistically significant (annual percentage change 0.5%, 95% confidence interval, -0.1, 1.1). Specific histologies that were increasing were lymphomas in individuals aged 20 to 64 years and in males aged 65 years or older, ependymomas in the population aged 20 to 64 years, nerve sheath tumors in males, and pituitary tumors in females. Increases that were not specific to any population subgroup were seen for glioblastoma, oligodendrogliomas, and astrocytomas, excluding not otherwise specified (NOS) tumors. Corresponding decreases were noted for NOS, astrocytoma NOS, and glioma NOS. Increasing incidence trends for lymphomas were consistent with previous literature. Improvements in diagnostic technology in addition to changes in classification and coding were likely to be responsible for decreases seen in incidence of NOS subgroups and corresponding increases in glioma subgroups. In contrast, the increases identified for ependymomas, nerve sheath tumors, and pituitary tumors were less likely to be artifacts of improvements in diagnosis, and they warrant further study.

Elevated Systemic Hepcidin and Iron Depletion in Obese Premenopausal Females

Hepcidin, the bodys main regulator of systemic iron homeostasis, is upregulated in response to inflammation and is thought to play a role in the manifestation of iron deficiency (ID) observed in obese populations. We determined systemic hepcidin levels and its association with body mass, inflammation, erythropoiesis, and iron status in premenopausal obese and nonobese women (n = 20/group) matched for hemoglobin (Hb). The obese participants also had liver and abdominal visceral and subcutaneous adipose tissue assessed for tissue iron accumulation and hepcidin mRNA expression. Despite similar Hb levels, the obese women had significantly higher serum hepcidin (88.02 vs. 9.70 ng/ml; P < 0.0001) and serum transferrin receptor (sTfR) (P = 0.001) compared to nonobese. In the obese women hepcidin was not correlated with serum iron (r = −0.02), transferrin saturation (Tsat) (r = 0.17) or sTfR (r = −0.12); in the nonobese it was significantly positively correlated with Tsat (r = 0.70) and serum iron (r = 0.58), and inversely with sTfR (r = −0.63). Detectable iron accumulation in the liver and abdominal adipose tissue of the obese women was minimal. Liver hepcidin mRNA expression was ∼700 times greater than adipose tissue production and highly correlated with circulating hepcidin levels (r = 0.61). Serum hepcidin is elevated in obese women despite iron depletion, suggesting that it is responding to inflammation rather than iron status. The source of excess hepcidin appears to be the liver and not adipose tissue. The ID of obesity is predominantly a condition of a true body iron deficit rather than maldistribution of iron due to inflammation. However, these findings suggest inflammation may perpetuate this condition by hepcidin‐mediated inhibition of dietary iron absorption.

Antiphospholipid antibodies, proteins C and S, and coagulation changes in sickle cell disease

The significance, interactions, and sources of coagulation abnormalities and their relationship to clinical severity and painful episodes in sickle cell disease are not clear. To evaluate this, we have examined various measures of coagulation in 37 patients with sickle cell disease (20 patients with HbSS disease and 17 patients with HbSC disease). Measurements have included isotypes of antiphospholipid antibodies (IgG, IgM, IgA) to specific phospholipids; proteins C (activity, total antigen) and S (activity, total and free antigen); measures of coagulation activation (prothrombin fragment 1.2, thrombin-antithrombin, fibrinopeptide A, d-dimers); indicators of clinical severity; and studies obtained during steady states and painful episodes. Results in HbSS disease showed that antiphospholipid antibodies were increased, with IgG phosphatidylserine showing the highest and most frequently increased levels (37% of patients). Protein C (activity) and protein S (activity, total, free antigen) were decreased (P<.01), and all measures of coagulation activation were increased (P<.001). In HbSC disease, antiphospholipid antibodies were normal, protein C (activity) and protein S (free antigen) were decreased (P<.001), and all measures of coagulation activation were increased (P<.02). A strong correlation was observed in HbSS disease between IgG-PS and d-dimers. Moderate correlations occurred between protein C activity and thrombin-antithrombin and fibrinopeptide A, between protein S activity and prothrombin fragment 1.2 and d-dimers, and between protein C and protein S activity. In HbSC disease, moderate and fewer correlations occurred. Significant differences between HbSS disease and HbSC disease were observed in aPLs, proteins C and S, and measures of coagulation activation. Measurements during steady states and during painful episodes were not significantly different. We conclude that the antiphospholipid antibody IgG-PS may contribute to coagulation activation in HbSS disease and that IgG-PS, protein C, and protein S relate to each other and jointly to measures of coagulation activation. The increased level of IgG-PS in HbSS disease most likely reflects exposure of the procoagulant phosphatidylserine on the surfaces of red cell-shed vesicles and sickle red cells, which would further affect coagulation activation. The significant differences in coagulation measures between HbSS disease and HbSC disease are consistent with differences in clinical severity between the diseases. The development of painful episodes does not appear to be related to the coagulation changes.

Gray Matter Atrophy in Patients With Ischemic Stroke With Cognitive Impairment

Background and Purpose— Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function. Methods— Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership. Results— Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance. Conclusions— These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures.

Plausibility of multivariate normality assumption when multiply imputing non-Gaussian continuous outcomes: a simulation assessment

Multiple imputation under the assumption of multivariate normality has emerged as a frequently used model-based approach in dealing with incomplete continuous data in recent years. Despite its simplicity and popularity, however, its plausibility has not been thoroughly evaluated via simulation. In this work, the performance of multiple imputation under a multivariate Gaussian model with unstructured covariances was examined on a broad range of simulated incomplete data sets that exhibit varying distributional characteristics such as skewness and multimodality that are not accommodated by a Gaussian model. Behavior of efficiency and accuracy measures was explored to determine the extent to which the procedure works properly. The conclusion drawn is that although the real data rarely conform with multivariate normality, imputation under the assumption of normality is a fairly reasonable tool, even when the assumption of normality is clearly violated; the fraction of missing information is high, especially when the sample size is relatively large. Although we discourage its uncritical, automatic and, possibly, inappropriate use, we report that its performance is better than we expected, leading us to believe that it is probably an underrated approach.