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ABSTRACT: To report our institution's experience using prone positioning for three-dimensional conformal radiotherapy (3D-CRT) to deliver post-lumpectomy whole breast irradiation (WBI) in a cohort of women with large and/or pendulous breasts, to determine the rate of acute and late toxicities and, more specifically, cosmetic outcomes. We hypothesized that using 3D-CRT for WBI in the prone position would reduce or eliminate patient and breast size as negative prognostic indicators for toxicities associated with WBI.
From 1998 to 2006, 110 cases were treated with prone WBI using 3D-CRT. The lumpectomy, breast target volumes, heart, and lung were contoured on all computed tomography scans. A dose of 45-50 Gy was prescribed to the breast volume using standard fractionation schemes. The planning goals were ≥95% of prescription to 95% of the breast volume, and 100% of boost dose to 95% of lumpectomy planning target volume. Toxicities and cosmesis were prospectively scored using the Common Terminology Criteria for Adverse Effects Version 3.0 and the Harvard Scale. The median follow-up was 40 months.
The median body mass index (BMI) was 33.6 kg/m(2), and median breast volume was 1396 cm(3). The worst toxicity encountered during radiation was Grade 3 dermatitis in 5% of our patient population. Moist desquamation occurred in 16% of patients, with only 2% of patients with moist desquamation outside the inframammary/axillary folds. Eleven percent of patients had Grade ≥2 late toxicities, including Grade 3 induration/fibrosis in 2%. Excellent to good cosmesis was achieved in 89%. Higher BMI was associated with moist desquamation and breast pain, but BMI and breast volume did not impact fibrosis or excellent to good cosmesis.
In patients with higher BMI and/or large-pendulous breasts, delivering prone WBI using 3D-CRT results in favorable toxicity profiles and high excellent to good cosmesis rates. Higher BMI was associated with moist desquamation, but prone positioning removed BMI and breast size as factors for poorer cosmetic outcomes. This series adds to the growing literature demonstrating that prone WBI may be advantageous in select patients.
International journal of radiation oncology, biology, physics 12/2011; 83(3):821-8. · 4.59 Impact Factor
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ABSTRACT: Viability assessment after acute myocardial infarction (MI) is important to guide revascularization. Two-dimensional strain echocardiography was shown to predict viability, but the method assumed that strain in each segment is independent of contiguous segments. The aim of this study was to test the hypotheses that segmental strain after MI is spatially correlated and that using a Bayesian approach improves the prediction of nonviable myocardium. Twenty-one subjects (mean age 58 +/- 12 years, 6 women) with MI >or=2 weeks before recruitment underwent 2-dimensional strain echocardiography and late gadolinium enhancement (LGE) cardiac magnetic resonance imaging within 48 hours of each other. The heart was divided into 16 segments, and longitudinal, radial, and circumferential strains were measured using software. Using similar segmentation, LGE was measured, and segments with >50% LGE were considered nonviable. Spearman's analyses were used to assess the spatial correlation of strain, and receiver-operating characteristic curve analysis was used to determine the prediction of nonviable myocardium without and with a Bayesian logistic spatial conditionally autoregressive (CAR) model. There was a significant spatial correlation in strain and LGE among segments, especially in the apex. Longitudinal strain was the best predictor of nonviability and was impaired in nonviable myocardium (-12.1 +/- 0.6%, -8.0 +/- 0.6%, and -4.6 +/- 1% for 0%, 1% to 50%, and >50% LGE, respectively, p <0.001). Use of the CAR model improved the area under the curve for the detection of nonviable myocardium (from 0.7 to 0.94). A CAR probabilistic score of 0.17 had 88% sensitivity and 86% specificity for detecting nonviable myocardium. In conclusion, longitudinal strain from 2-dimensional strain echocardiography can predict myocardial viability after MI, and exploiting spatial correlations in segmental strain using Bayesian CAR modeling enhances the ability of 2-dimensional strain to predict nonviable myocardium.
The American journal of cardiology 10/2009; 104(8):1023-9. · 3.58 Impact Factor
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ABSTRACT: Reactivation of the cell cycle, including DNA replication, might play a major role in Alzheimer's disease. In this study, we report that the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP) or of the APP intracellular domain (AICD) into nerve growth factor (NGF)-differentiated PC12 cells or rat primary cortical neurons increased mRNA and protein levels of cyclin D1 and cyclin B1. Treatment with lithium chloride (a glycogen synthase kinase-3beta inhibitor) down-regulated cyclin B1 induced by Swe-APP expression but up-regulated cyclin D1 expression induced by Swe-APP, suggesting that glycogen synthase kinase-3beta activity is involved in these expression changes of cyclins D1 and B1. Swe-APP, which is a prevailing cause of familial Alzheimer's disease, is well known to increase amyloid beta peptide production both in vitro and in vivo, but the underlying molecular means whereby it leads to the pathogenesis of AD remains unknown. The finding that cyclin D1 and B1 expressions were up-regulated by Swe-APP in in vitro cultured cells was substantiated in the brain tissues of Tg2576 mice, which harbor the Swe-APP mutation. These results suggest that some disturbances in cell cycle regulation may be involved in Swe-APP or AICD-induced neurodegeneration and that these contribute to the pathogenesis of AD.
Journal of Neuroscience Research 05/2008; 86(11):2476-87. · 2.74 Impact Factor
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ABSTRACT: The AICD (APP intracellular Domain) and C31, caspase-cleaved C-terminal fragment of APP, have been found in Alzheimer's disease (AD) patients' brains and have been reported to induce apoptosis in neuronal cells. In recent, the C-terminal fragments of amyloid precursor protein (APP-CTs) have been reported to form a complex with Fe65 and the histone acetyltransferase Tip60 and are thought to be involved in gene transcription. In this study, based on the hypothesis that APP-CTs might exert neurotoxicity by inducing some gene transcription, we investigated the effects of APP-CTs on histone acetylation which indicates that transcription is actively going on and also on the relationship between histone acetylation and the cytotoxicity induced by APP-CTs in nerve growth factor (NGF)-differentiated PC12 cells and rat primary cortical neurons. Here we demonstrate that the expression of APP-CTs [C31, AICD (C59) and C99] induces increases in acetylation of histone 3 and histone 4 and that treatment with sodium butyrate, an inhibitor of histone deacetylase, significantly enhances the cytotoxicity induced by APP-CTs. The acetylation of histone plays an important role in allowing regulatory proteins to access DNA and is likely to be a major factor in the regulation of gene transcription. Taken together, our results suggest that APP-CTs exert neurotoxicity by transcription-dependent mechanisms and this might contribute to the pathogenesis of AD.
Journal of Neuroscience Research 02/2004; 75(1):117-24. · 2.74 Impact Factor
