We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).
A total of 379 eligible women with estrogen ...receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded.
Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice.
RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Electrocoating at constant current is less sensitive to moisture and oxygen than electrocoating at controlled potential, which makes it more interesting for industrial implementation. The ...galvanostatic electrocoating of carbon fibres with Poly(methylmethacrylate) (PMMA) was therefore studied and compared to the well researched potentiostatic electrocoating procedure. The influence of different experimental parameters on the coating efficiency was investigated in order to identify the mechanisms that are involved in the cathodic electrocoating at constant current. It could be confirmed that the involved mechanisms differ from potentiostatic electrocoating and it was found that galvanostatic electrocoating is more efficient at ambient conditions compared to potentiostatic electrocoating. Polymer layers that cover the entire carbon fibre surface could be achieved in a continuous process by galvanostatic electrocoating under ambient conditions.
Aims With the increasing availability of new drugs for the treatment of insulin resistance in patients with Type 2 diabetes, simple methods for their identification is an important challenge. The ...aim of our study was to compute a new algorithm for estimating insulin resistance in a routine clinical setting.
Methods Clinical data and blood samples were collected from 4265 Type 2 diabetic patients from 149 clinical sites. A clinical algorithm to estimate insulin resistance was developed by stepwise multiple regression analysis. The new generated score was compared with the HOMAIR‐score, calculated from fasting insulin and glucose levels measured in a central laboratory. In a subgroup of 48 patients, the score was verified against a frequently sampled intravenous glucose tolerance test with subsequent modified minimal model analysis according to Bergman.
Results Multiple regression analysis revealed fasting blood glucose, BMI, triglycerides and HDL as the most powerful predictors of insulin resistance which were used for further computation of the IRIS II score. A significant overall correlation was found between the HOMAIR‐score and the new clinical IRIS II score (r = 0.42; P < 0.0001). Compared with HOMAIR, the new score revealed a specificity of 0.95, a sensitivity of 0.34 and a positive predictive value of 0.95. This was in good agreement with the subset analysis of the intravenous glucose tolerance test, where a sensitivity of 0.37 and a specificity of 0.85 of the IRIS II score was calculated. Patients with insulin resistance according to the IRIS II score revealed an increased odds ratio for overall vascular complications (1.28; 1.11–1.46; P < 0.001).
Conclusions The new IRIS II score can identify insulin resistance in Type 2 diabetic patients with high predictive value and high specificity.
Abstract
Aim: TACE with Irinotecan loaded drug-eluting beads has shown activity in colorectal liver metastases. A neoangiogenic reaction due to ischemia may be among the factors interfering with its ...effectiveness. In this study we evaluated the changes in VEGF-A serum level as a potential surrogate for this neoangiogenic reaction in patients treated with TACE.
Methods: Patients with predominant and life threatening liver metastases from CRC which were refractory to all drugs approved for metastasized CRC and documented tumor progression during or shortly after the last chemotherapy, were prospectively treated with DEBIRI with a size of 100-300 µm. Therapy was applied by a temporary catheter placed in the liver arteries. Usually each lobe of the liver was treated two times with an interval of 4 weeks. Each treatment of one liver lobe was performed with 1 vial of the DC-Beads loaded with 100 mg Irinotecan. Blood samples to measure the VEGF-A-serum levels were taken before TACE and at days 8, 15 and 22 after first treatment.
Results: Complete blood samples to evaluate the VEGF-A-level were taken from 37 patients (24 m/13 f; median age 64 y) from 2/11 to 5/13. 51% of patients had an increase of the VEGF-A-level compared to baseline of median 75 % after 21 days, whereas 49% of patients had a decrease of the VEGF-A-Level of median 34% after 21 days, respectively. The changes of the VEGF-A-level at day 8 were predictive for the following course of the levels. Baseline levels were significantly higher in patients pretreated with Bevacizumab within the last 9 weeks prior to first DEBIRI (p < 0,0001). A decrease or only slight increase of the VEGF-A-level at day 8 was found in these patients, compared to those with a more prolonged interval or to Bevacizumab-naïve patients (p < 0.0001).
Conclusions: These findings show different behavior of the serum VEGF-A-levels after DEBIRI-TACE, suggesting that the occlusion of blood vessels and subsequent ischemia induces neo-angiogenesis due to VEGF-A in a subset of 51% of these patients. VEGF-A -level decrease in patients with a Bevacizumab therapy within the last 9 weeks prior to first TACE may be due to a neoangiogenesis-pathway other than VEGF-mediated. These results could implicate that drugs targeting the VEGF-pathway might be effective as an additive therapy to chemoembolization in a subset of patients e.g. those with a low baseline VEGF-A-level.
Disclosure: S. Pluntke: Consultancy Terumo Germany. All other authors have declared no conflicts of interest.
The socioeconomic value of prophylaxis of acute exacerbations in patients with chronic recurrent bronchitis with N‐acetylcysteine (NAC) in comparison to no prophylaxis is the subject of this ...analysis. In the case of an exacerbation, therapy with the antibiotic amoxicillin was presumed.
METHODS: This decision tree analysis is based on a meta‐analysis, which described the probability and the frequency of an exacerbation either in the case of prophylaxis with NAC or no prophylaxis. Three sensitivity analyses have been carried out. To check the stability of the results of this cost‐utility analysis, therapy with amoxicillin was replaced by the antibiotic doxycycline. The daily costs of NAC, which have a considerable influence on the direct costs, were also varied. Finally, the influence of the probability of impatient therapy was analyzed.
RESULTS: Documented over a period of one year, prophylaxis with NAC resulted in direct costs of 438.42 DM, whereas no prophylaxis caused direct costs of 266.82 DM. On the basis of indirect costs, prophylaxis with NAC caused costs of 2,177.36 DM and no prophylaxis caused costs of 2,569.42 DM. The result of projecting these costs for the estimated 122,830 patients with chronic recurrent bronchitis in the Federal Republic of Germany reveals a potential of savings of total costs of approximately 27.1 million DM in the case of a change from no prophylaxis to prophylaxis with NAC.
CONCLUSION: This decision tree analysis reveals that prophylaxis with NAC causes higher direct costs but in long term it reduces the indirect costs by reducing the time off work.
Ist die Expression von „secreted protein, acidic an drich in cysteine (SPARC)“ ein prädiktiver Wert bei Patientinnen mit metastasiertem Mammakarzinom (MBC) unter Therapie mit nab-Paclitaxel?
In ...dieser prospektiven Studie erhielten 44 Patientinnen mit progressivem MBC eine Therapie mit nab-Paclitaxel weekly. Die SPARC-Expression wurde an den Tumorzellen und im Stroma immunhistochemisch bestimmt sowohl am Primärtumor (n = 37) als auch an der Metastase (n = 22). Die Bestimmung der SPARC-Konzentration im Serum erfolgte vor dem 1. und 2. Zyklus sowie bei Progress. Anschließend wurde die SPARC-Expression und SPARC-Serumkonzentration mit verschiedenen klinischen Endpunkten korreliert (Gesamtansprechrate (ORR), Krankheitskontrollrate (DCR), klinische Benefitrate (CBR), progressionsfreies Überleben (PFS), Gesamtüberleben (OS)).
Nab-Paclitaxel wurde als Erstlinientherapie bei 19 (43%) Patientinnen gegeben, als Zweitlinientherapie bei 11 (25%) und als Dritt- bzw. Mehrlinientherapie bei 14 (32%) Patientinnen. Insgesamt ergaben sich eine ORR von 23%, eine DCR von 66% und eine CBR von 36%. Das mediane PFS betrug 5,7 Monate. Das mediane OS betrug 10,2 Monate. Eine SPARC-Expression mit einem IRS ≥3 an der Tumorzelle wurde bei 5/37 (14%) Patientinnen im Primärtumor und bei 1/22 (5%) Patientinnen in der Metastase detektiert, eine positive SPARC-Expression von 2+ im Stroma in 28/37 (76%) Patientinnen im Primärtumor und 16/22 (73%) Patientinnen in der Metastase. Es fand sich keine eindeutige Assoziation zwischen der SPARC-Expression im Primärtumor, in der Metastase oder der SPARC-Konzentration im Serum und einem der oben genannten klinischen Endpunkte auch unter Berücksichtigung verschiedener Schwellenwerte für eine SPARC-Positivität.
Die Wirksamkeit von nab-Paclitaxel beim MBC scheint nicht mit der SPARC-Expression im Tumorgewebe oder der SPARC-Serum-Konzentration assoziiert zu sein.
Stroke is the third leading cause of death in Germany and the major source of disability in persons older than 60 years of age.
OBJECTIVE: In a retrospective analysis, the cost structure of the ...screening of risk factors for stroke was inquired. This analysis is a cost‐effectivness analysis and centred around the question how many strokes are avoided as a result of the screening, expressed in a cost‐effective ratio.
METHODS: Five risks factors for stroke are distinguished. These risk factors can occur on their own or together and were (a) controlled, (b) not controlled, or (c) not obvious. A decision tree with 90 endpoints was constructed. The probability of stroke for the five risk factors was taken from a study describing a risk profile from the Framingham population. The period of the model was 10 years. Health care costs included in the model were all medical costs (hospitalization, drug costs, etc. and indirect costs (absence from workplace, burial allowance).
RESULTS: Per patient the screening caused direct costs of 1,272,93 DM and indirect costs of 1,034.71 DM. Without a screening there are direct costs of 1,173.65 DM and indirect costs of 948.52 DM. Screening is hence the cost‐intensive alternative. The cost‐effective ratio is the difference of direct costs divided by avoided strokes. To avoid one stroke, 150,000.00 DM must be invested. For a better comprehension of the results, sensitivity analyses were conducted to determine the influence of the efficacy on the effectiveness adjusted costs of stroke and the effects of the frequency of modified assumptions of the model.
CONCLUSION: This decision tree analysis reveals that screening of risk factors for stroke is not the. If the costs of stroke were 182,000.00 DM, then screening would be the lowest cost alternative.
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