High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.
Receiver operating characteristic (ROC) curves have been useful in two-group classification problems. In three- and multiple-class diagnostic problems, an ROC surface or hyper-surface can be constructed. The volume under these surfaces can be used for inference using bootstrap techniques or U-statistics theory. In this article, ROC surfaces and hyper-surfaces are defined and their behaviour and utility in multi-group classification problems is investigated. The formulation of the problem is equivalent to what has previously been proposed in the general multi-category classification problem but the definition of ROC surfaces here is less complex and addresses directly the narrower problem of ordered categories in the three-class and, by extension, the multi-class problem applied to continuous and ordinal data. Non-parametric manipulation of both continuous and discrete test data and comparison between two diagnostic tests applied to the same subjects are considered. A three-group classification example in the context of HIV neurological disease is presented and the results are discussed.
Objective
To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of highly active antiretroviral therapy (HAART).
Design
This study is an observational cohort study.
Methods
MRS was performed in 268 patients: HIV-negative controls (N=28), HIV-positive neuroasymptomatic (NA) subjects (N=124), and subjects with AIDS Dementia Complex (ADC; N=50) on stable ART with a mean duration of infection of 12 years and CD4 of 309 cells/mm3. Four metabolites were measured over creatine (Cr): N-acetyl aspartate (NAA), marker of neuronal integrity; Choline (Cho), myoinositol (MI), markers of inflammation, and glutamate and glutamine (Glx) in the basal ganglia (BG), frontal white matter (FWM) and mid-frontal Cortex (MFC). Analyses included ANOVA, ANCOVA, linear and nonparametric regression models.
Results
Cognitive impairment was found in 48% of HIV infected subjects. Both HIV positive groups showed significant increases in MI/Cr or Cho/Cr in all brain regions when compared to controls; a significant decrease in Glx/Cr in the FWM was observed in the NA group; only ADC subjects showed a significant reduction in NAA/ Cr although a significant trend for decreasing NAA/Cr in the BG was found across the groups. Effects related to aging and duration of infection but not central nervous system penetration effectiveness (CPE) were observed.
Conclusions
Brain inflammatory changes remain ubiquitous among HIV-infected subjects whereas neuronal injury occurs predominantly in those with cognitive impairment. Together these findings indicate that despite the widespread use of HAART, HIV-associated cognitive impairment and brain injury persist in the setting of chronic and stable disease.
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