Correlation between Histopathological Prognostic Tumor Characteristics and [18F]FDG Uptake in Corresponding Metastases in Newly Diagnosed Metastatic Breast Cancer.

BACKGROUND: In metastatic breast cancer (MBC), [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [18F]FDG uptake in corresponding metastases. PATIENTS AND METHODS: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [18F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [18F]FDG uptake was expressed as maximum standardized uptake value (SUVmax) and results were expressed as geometric means. RESULTS: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [18F]FDG uptake (estimated geometric mean SUVmax 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [18F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUVmax 6.8 and 10.0, respectively; p = 0.0058). Although [18F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUVmax 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. CONCLUSIONS: [18F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [18F]FDG uptake, [18F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332).

The dream of a one-stop-shop: Meta-analysis on myocardial perfusion CT.

PURPOSE: To determine the diagnostic performance of computed tomography (CT) perfusion techniques for the detection of functionally relevant coronary artery disease (CAD) in comparison to reference standards, including invasive coronary angiography (ICA), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). MATERIALS AND METHODS: PubMed, Web of Knowledge and Embase were searched from January 1, 1998 until July 1, 2014. The search yielded 9475 articles. After duplicate removal, 6041 were screened on title and abstract. The resulting 276 articles were independently analyzed in full-text by two reviewers, and included if the inclusion criteria were met. The articles reporting diagnostic parameters including true positive, true negative, false positive and false negative were subsequently evaluated for the meta-analysis. Results were pooled according to CT perfusion technique, namely snapshot techniques: single-phase rest, single-phase stress, single-phase dual-energy stress and combined coronary CT angiography [rest] and single-phase stress, as well the dynamic technique: dynamic stress CT perfusion. RESULTS: Twenty-two articles were included in the meta-analysis (1507 subjects). Pooled per-patient sensitivity and specificity of single-phase rest CT compared to rest SPECT were 89% (95% confidence interval [CI], 82-94%) and 88% (95% CI, 78-94%), respectively. Vessel-based sensitivity and specificity of single-phase stress CT compared to ICA-based >70% stenosis were 82% (95% CI, 64-92%) and 78% (95% CI, 61-89%). Segment-based sensitivity and specificity of single-phase dual-energy stress CT in comparison to stress MRI were 75% (95% CI, 60-85%) and 95% (95% CI, 80-99%). Segment-based sensitivity and specificity of dynamic stress CT perfusion compared to stress SPECT were 77% (95% CI, 67-85) and 89% (95% CI, 78-95%). For combined coronary CT angiography and single-phase stress CT, vessel-based sensitivity and specificity in comparison to ICA-based >50% stenosis were 84% (95% CI, 67-93%) and 93% (95% CI, 89-96%). CONCLUSION: This meta-analysis shows considerable variation in techniques and reference standards for CT of myocardial blood supply. While CT seems sensitive and specific for evaluation of hemodynamically relevant CAD, studies so far are limited in size. Standardization of myocardial perfusion CT technique is essential.

Hemodynamic significance of coronary stenosis by vessel attenuation measurement on CT compared with adenosine perfusion MRI.

PURPOSE: We assessed the association between corrected contrast opacification (CCO) based on coronary computed tomography angiography (cCTA) and inducible ischemia by adenosine perfusion magnetic resonance imaging (APMR). METHODS: Sixty cardiac asymptomatic patients with extra-cardiac arterial disease (mean age 64.4 ± 7.7 years; 78% male) underwent cCTA and APMR. Luminal CT attenuation values (Hounsfield Units) were measured in coronary arteries from proximal to distal, with additional measurements across sites with >50% lumen stenosis. CCO was calculated by dividing coronary CT attenuation by descending aorta CT attenuation. A reversible perfusion defect on APMR was considered as myocardial ischemia. RESULTS: In total, 169 coronary stenoses were found. Seven patients had 8 perfusion defects on APMR, with 11 stenoses in corresponding vessels. CCO decrease across stenoses with hemodynamic significance was 0.144 ± 0.112 compared to 0.047 ± 0.104 across stenoses without hemodynamic significance (P=0.003). CCO decrease in lesions with and without anatomical stenosis was similar (0.054 ± 0.116 versus 0.052 ± 0.101; P=0.89). Using 0.20 as preliminary CCO decrease cut-off, hemodynamic significance would be excluded in 82.9% of anatomical stenoses. CONCLUSIONS: CCO decrease across coronary stenosis is associated with myocardial ischemia on APMR. CCO based on common cCTA data is a novel method to assess hemodynamic significance of anatomical stenosis.

Skin autofluorescence, a non-invasive marker for AGE accumulation, is associated with the degree of atherosclerosis.

INTRODUCTION: Advanced glycation endproducts (AGEs) may be involved in the development of atherosclerosis, beyond diabetes and renal disease. Skin autofluorescence (AF) is a non-invasive marker for AGEs. We examined whether skin AF is increased in (subclinical) atherosclerosis and associated with the degree of atherosclerosis independent of diabetes and renal function. METHODS: A cross-sectional study of 223 patients referred for primary (n = 163) or secondary (n = 60) prevention between 2006 and 2012 was performed. Skin AF was measured using the AGE-Reader. Ultrasonography was used to assess plaques in carotid and femoral arteries and computed tomography for the calculation of the coronary artery calcium score (CACS; in primary prevention only). Primary prevention patients were divided into a group with subclinical atherosclerosis defined as >1 plaque or CACS>100 (n = 67; age 53 year [interquartile range 48-56]; 49% male) and without (controls; 96; 43 [38-51]; 55%). Secondary prevention were patients with peripheral arterial disease (60; 64 [58-70]; 73%). RESULTS: Skin AF was higher in subclinical and clinical atherosclerosis compared with controls (skin AF 2.11 [interquartile range 1.83-2.46] and 2.71 [2.15-3.27] vs. 1.87 [1.68-2.12] respectively; P = 0.005 and <0.001). In a multivariate analysis, the association of skin AF with the atherosclerosis categories was independent of age, sex, diabetes, presence of the metabolic syndrome, Framingham Risk Score, and renal function. Skin AF correlated with most cardiovascular risk factors, Framingham risk score, and IMT and CACS. CONCLUSIONS: Skin AF is increased in documented subclinical and clinical atherosclerosis, independent of known risk factors such as diabetes and renal disease. These data suggest that AGEs may be associated with the burden of atherosclerosis and warrant a prospective study to investigate its clinical usability as a risk assessment tool for primary prevention.

Diagnostic performance of coronary CT angiography for stenosis detection according to calcium score: systematic review and meta-analysis.

OBJECTIVES: A systematic review and meta-analysis to assess sensitivity and specificity of coronary CT angiography (CCTA) for significant stenosis at different degrees of coronary calcification. METHODS: A literature search was performed including studies describing test characteristics of CCTA for significant stenosis, performed with at least 16-MDCT and according to calcium score (CS). Invasive coronary angiography was the reference standard. Pooled sensitivity and specificity of CCTA by CS categories and CT equipment were calculated. RESULTS: Of 14,121 articles, 51 studies reported on the impact of calcium scoring on diagnostic performance of CCTA and could be included in the systematic review. Twenty-seven of these studies (5,203 participants) were suitable for meta-analysis. On a patient-basis, sensitivity of CCTA for significant stenosis was 95.8, 95.6, 97.6 and 99.0% for CS 0-100, 101-400, 401-1,000 and >1,000 respectively. Specificity was 91.2, 88.2, 50.6 and 84.0% respectively. Specificity of CCTA was significantly lower for CS 401-1,000 due to lack of patients without significant stenosis. Sensitivity and specificity of 16-MDCT were significantly lower compared to more modern CT systems. CONCLUSIONS: Even in cases of severe coronary calcification, sensitivity and specificity of CCTA for significant stenosis are high. With 64-MDCT and newer CT systems, a CS cut-off for performing CCTA no longer seems indicated. KEY POINTS: Decisions about performing coronary CT angiography (CCTA) sometimes depend on calcium scoring. CCTA is highly sensitive for coronary stenosis. With 16-MDCT, however, heavy calcification reduces specificity for significant stenosis. For 64-MDCT (and above), CCTA has high specificity, even with severe coronary calcification.