Independent Adjudication of Symptomatic Heart Failure With the Use of Doxorubicin and Cyclophosphamide Followed by Trastuzumab Adjuvant Therapy: A Combined Review of Cardiac Data From the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 Clinical Trials
ABSTRACT An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addition of trastuzumab to standard adjuvant chemotherapy.
The committee was composed of six independent oncologists and cardiologists. A retrospective review of patients with a cardiac event was performed by the primary investigators of the trials. The ACREC prospectively established criteria for determining a symptomatic heart failure event. Recovery status was determined from documented resolution of signs and symptoms. Potential risk factors were also assessed.
Medical records for a total of 173 patients were reviewed: 40 in the chemotherapy-alone arm and 133 in the trastuzumab arm. Trastuzumab-treated patients had a 2.0% incidence of symptomatic heart failure events compared with 0.45% in the chemotherapy-alone arm. Complete or partial recovery was observed in 86.1% of trastuzumab-treated patients with symptomatic heart failure events. Of five patients who died, only one patient had received trastuzumab. Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment, and trastuzumab treatment.
The incidence of symptomatic heart failure events is 2.0% in patients treated with adjuvant trastuzumab, and the majority of these patients recover with appropriate treatment.
- SourceAvailable from: Michal Jank
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- "Anticancer efficacy is complicated by a new type of heart failure (Cheng and Force 2010; Perez 2008). There is evidence that trastuzumab (Criscitiello and Curigliano 2013; Procter et al. 2010; Russell et al. 2010), lapatinib (Perez et al. 2008a), and pertuzumab (Lenihan et al. 2012) blocking the ErbB2/ HER2-dependent signaling pathway may lead to the deterioration of left ventricular cardiac function. Cardio-oncology, a new scientific discipline, aims at trying to find methods to prevent iatrogenic myocardial dysfunction during anticancer treatment (Curigliano et al. 2012; Opolski et al. 2011). "
ABSTRACT: Anticancer treatment with the human epidermal growth factor receptor (HER) 2 inhibitors can lead to significant myocardial dysfunction. The primary aim of the study was to estimate the possible association between gene expression in the ErbB signaling pathway and selected clinical event data in patients with acute heart failure. Twenty-four patients (19 males), aged 68.6 ± 12.3 years, were diagnosed and treated due to acute heart failure. The globaltest method was used for the correlation between blood nuclear cells' gene expression in the ErbB pathway (KEGG pathway id 04012) and important clinical data. Decreased expression of ErbB2/HER2 was found to be associated with the release of troponin and the need for inotropic support, whereas decreased neuregulin 1 (NRG1) expression was found to be associated with a decrease of ejection fraction below 40 % (globaltest p-value < 0.05). In summary, the ErbB signaling pathway and, especially, HER2/ErbB2 receptor expression are significantly associated with some of the recognized, clinically significant parameters of patients with acute heart failure. Evaluation of the molecular function of the HER2 receptor may be essential for the prognosis and targeted therapy of heart diseases.Journal of applied genetics 08/2013; 54(4). DOI:10.1007/s13353-013-0164-y · 1.48 Impact Factor
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ABSTRACT: A new approach for parallelism analysis and extraction of digital signal processing algorithms is introduced. The high level description of the input is given in CIRCAL. A dependency graph of the problem is constructed to check existence of cycles. Loops in the dependency graph are parallelized. The approach is illustrated by an exampleSignals, Systems and Computers, 1994. 1994 Conference Record of the Twenty-Eighth Asilomar Conference on; 01/1994
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ABSTRACT: In this paper we present an application of the Wold-Cramer representation of non-stationary signals to system identification and modeling. According to the Wold-Cramer representation, a non-stationary signal can be expressed as an infinite sum of sinusoids with time-varying random magnitudes and phases. For the identification of linear time-invariant (LTI) systems, we relate the Wold-Cramer representations of the system's input and output to obtain estimates of the magnitude and phase frequency responses of the system. Our procedure permits the identification of non-minimum phase systems. Furthermore, we show that when the system output is noisy, and the noise is stationary it is possible to avoid the effects of the noise in the identification. If the noise is non-stationary and Gaussian, one needs to consider the evolutionary bispectrum, recently introduced by Priestley, to get rid of the noise. The analysis also provides a model for a non-stationary signal, as the output of a cascade of a linear time-varying and a linear time-invariant systems with stationary white noise as input. To illustrate our procedure, we present a simulation of the identification of a non-minimum phase systemTime-Frequency and Time-Scale Analysis, 1994., Proceedings of the IEEE-SP International Symposium on; 11/1994