Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial.

BACKGROUND: The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. METHOD: An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. RESULTS: Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to -17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial. CONCLUSION: In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease.

Detection of circulating tumor cells in blood of metastatic breast cancer patients using a combination of cytokeratin and EpCAM antibodies.

BACKGROUND: Circulating tumor cells (CTCs) are detectable in peripheral blood of metastatic breast cancer patients (MBC). In this paper we evaluate a new CTC separation method based on a combination of anti-EpCAM- and anti-cytokeratin magnetic cell separation with the aim to improve CTC detection with low target antigen densities. METHODS: Blood samples of healthy donors spiked with breast cancer cell line HCC1937 were used to determine accuracy and precision of the method. 10 healthy subjects were examined to evaluate specificity. CTC counts in 59 patients with MBC were measured to evaluate the prognostic value on overall survival. RESULTS: Regression analysis of numbers of recovered vs. spiked HCC1937 cells yielded a coefficient of determination of R(2) = 0.957. The average percentage of cell recovery was 84%. The average within-run coefficient of variation for spiking of 185, 85 and 30 cells was 14%. For spiking of 10 cells the within-run CV was 30%. No CTCs were detected in blood of 10 healthy subjects examined. A standard threshold of 5 CTC/7.5 ml blood as a cut-off point between risk groups led to a highly significant prognostic marker (p < 0.001). To assess the prognostic value of medium CTC levels we additionally considered a low (CTC-L: 0 CTC), a medium (CTC-M: 1-4 CTC) and a high risk group (CTC-H: ≥5 CTC). The effect of this CTC-LMH marker on overall survival was significant as well (p < 0.001). A log-ratio test performed to compare the model with 3 vs. the model with 2 risk groups rejected the model with 2 risk groups (p = 0.026). For CTC as a count variable, we propose an offset reciprocal transformation 1/(1 + x) for overall survival prediction (p < 0.001). CONCLUSIONS: We show that our CTC detection method is feasible and leads to accurate and reliable results. Our data suggest that a refined differentiation between patients with different CTC levels is reasonable.

Potential of feature selection methods in heart rate variability analysis for the classification of different cardiovascular diseases.

In this study heart rate variability (HRV) analysis was applied to characterize patients suffering from coronary heart disease (CHD), dilated cardiomyopathy (DCM) and patients who had survived an acute myocardial infarction (MI). On the basis of several HRV parameters, an optimal discrimination between the different kinds of cardiovascular diseases and between the diseases and healthy controls (HC) was derived by feature selection and linear classification. For each task a small favourable subset of a set of 33 potentially interesting HRV measures was selected with the intention of improving the diagnostic value and facilitating the physiological interpretation of HRV analysis. Time- and frequency-domain parameters as well as parameters from non-linear dynamics were included in the analysis. With the expectation that different diseases are characterized by different phenomena, feature selection was applied for each task separately. Using the features optimal for one task to another task can reveal a loss in performance, but it turned out that one specific parameter set (set1: normalized low frequency LF/P and a non-linear variability measure WPSUM13) was applicable for all tasks, where diseased and healthy subjects have to be distinguished, without significant reduction in performance. This set seems to be a general marker for pathologic changes in HRV and might be used for early detection of heart diseases. The classification between different heart diseases requires another parameter set (set2: meanNN and sdaNN, reflecting the steady state behaviour of the heart rate and long and short term SEAR describing the spectral composition). However, the use of set1 for the separation of different kinds of diseases, where set2 is appropriate, led to significant reduction in performance and vice versa. This observation may be important for future developments of HRV measures especially suitable for the assessment of disease severity.

Heart rate variability before the onset of ventricular tachycardia: differences between slow and fast arrhythmias.

BACKGROUND: We tested whether or not heart rate variability (HRV) changes can serve as early signs of ventricular tachycardia (VT) and predict slow and fast VT in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: We studied the ICD stored 1000 beat-to-beat intervals before the onset of VT (131 episodes) and during a control time without VT (74 series) in 63 chronic heart failure ICD patients. Standard HRV parameters as well as two nonlinear parameters, namely 'Polvar10' from symbolic dynamics and the finite time growth rates 'Fitgra9' were calculated. Comparing the control and the VT series, no linear HRV parameter showed a significant difference. The nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (for time series with less than 10% ectopy, P<0.05). Subdividing VT into fast (cycle length 270 ms) events, we found that the onset of slow VT was characterized by a significant increase in heart rate, whereas fast VT was triggered during decreased heart rates, compared to the control series. CONCLUSIONS: Our data may permit the development of automatic ICD algorithms based on nonlinear dynamic HRV parameters to predict VT before it starts. Furthermore, they may facilitate improved prevention strategies.

Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy.

Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non-invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 +/- 32.6 vs. 9.8 +/- 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 +/- 0.60 vs. 2.07 +/- 1.04 mmHg BBI(-1) (BBI, beat-to-beat interval), P < 0.05), as was HR-TS (8.46 +/- 7.90 vs. 30.73 +/- 22.90 ms BBI(-1), P < 0.01). HR-TO was significantly higher in IDC patients (-0.56 +/- 2.19 vs. -5.52 +/- 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC.