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Background/Aim: Sunitinib is a tyrosine kinase inhibitor routinely used as first-line therapy in metastatic renal cell carcinoma (mRCC). Emerging evidence suggests that microRNAs (miRNAs) could be suitable biomarkers with predictive potential in mRCC. The aim of this study was to identify miRNA-based predictive biomarkers of therapy response to avoid unnecessary therapy to non-responding patients. Patients and Methods: High-throughput miRNA microarray profiling was performed on a cohort of 47 patients treated with sunitinib. Validation of candidate miRNAs was carried out on an independent cohort of 132 mRCC patients using qRT-PCR. Results: Out of 158 miRNAs (65 down-regulated, 93 up-regulated), six miRNAs were chosen for independent validation and miR-376b-3p was confirmed to be differentially expressed in tumors of patients with primary resistance versus long-term response (p

The first-line therapy of patients with RAS wild-type (WT) non-resectable metastatic colorectal cancer (mCRC) is usually 5-fluorouracil-based chemotherapy with either bevacizumab or an anti-epidermal growth factor receptor (EGFR). The addition of anti-EGFR antibodies is commonly delayed in clinical practice because of late RAS testing results. Our objective was to evaluate the impact on overall survival (OS) of a delayed anti-EGFR introduction strategy. This study pooled the data of two large retrospective studies. Patients with RAS WT non-resectable mCRC, treated in first line by a doublet chemotherapy with an anti-EGFR introduced with a delay of 2 to 4 cycles, were compared to an anti-EGFR and to an anti-VEGF that was introduced immediately. Patients numbering 305 in the delayed anti-EGFR group, 401 in the immediate anti-EGFR group, and 129 in the immediate anti-VEGF group were analyzed. After propensity scoring, there was no difference between the characteristics of the three groups. Median OS was 28.6 months (95% CI: 23.5–34.1) in the immediate anti-EGFR group, 35.1 (95% CI: 29.9–43.5) in the delayed anti-EGFR group, and 32.4 (95% CI: 25.4–44.8) in the immediate anti-VEGF group. There was no significant difference concerning median OS (p = 0.24) or progression-free survival (p = 0.56). This study suggests that delaying the introduction of an anti-EGFR has no deleterious impact on survival compared to the immediate introduction of an anti-VEGF or of an anti-EGFR.

The article analyzes the possible impacts of the fully-funded (FF) pension system (the so-called Chilean model), which was introduced in the Czech Republic in 2012, on future pensions of contributors to the system and on state expenditures related to the pension system reform. The author performed calculations for 3 model examples of individuals who would participate solely in the FF and also of individuals who would contribute to both the pay-as-you-go (PAYG) and the FF during their lives. The calculations in all model examples were made for 4 average real annual interest rates and for 4 standardised income levels. The income replacement rates of the examined individuals were compared with the existing PAYG and with a hypothetical balanced PAYG. The aim was to determine the minimum rate of the pension funds' appreciation from whichthe transition to the FF would be profi table for all examined individuals. The article also attempts to identify the duration of the transition period, the moment after which the FF would become budget-neutral, and the approximate cost of the transition process.

General elections in Chile in the autumn of 2013 have unleashed a discussion about the shortcomings of the Chilean pension system and the necessary changes. Radical solutions contains various forms of return of the PAYG system. The paper deals with the preparation and the main implication of the pension reform in 1981 which led to the transition from the PAYG system to the capital system. Thanks to the reconstruction of the time series from the 70s and 80s of the 20th century using the latest data from 2013 and own calculations the article confirmed that the transition meant a noticeable increase in pensions for everybody included in the system. This outcome is driven mainly by the lower tax burden, generated savings and positive impact, particularly on the country's GDP and government budget. The paper also summarize the available knowledge about the pension reform in Chile in the Czech language.

Background: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. Objective: To determine the effects of corticosteroids on major clinical outcomes of DMD in a large multinational cohort of genetically confirmed DMD patients. Methods: In this cross-sectional study we analysed clinical data from 5345 genetically confirmed DMD patients from 31 countries held within the TREAT-NMD global DMD database. For analysis patients were categorised by corticosteroid background and further stratified by age. Results: Loss of ambulation in non-steroid treated patients was 10 years and in corticosteroid treated patients 13 years old (p = 0.0001). Corticosteroid treated patients were less likely to need scoliosis surgery (p < 0.001) or ventilatory support (p < 0.001) and there was a mild cardioprotective effect of corticosteroids in the patient population aged 20 years and older (p = 0.0035). Patients with a single deletion of exon 45 showed an increased survival in contrast to other single exon deletions. Conclusions: This study provides data on clinical outcomes of DMD across many healthcare settings and including a sizeable cohort of older patients. Our data confirm the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-centre collaboration in the rare disease field. This work was supported by TREAT-NMD operating grants, FP6 LSHM-CT-2006-036825, 20123307 UNEW FY2013 and AFM 16104. Further support came from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 305444 (RD-Connect) and 305121 (Neuromics) and Medical Research Council UK (reference G1002274, grant ID 98482). Sí

A retrospective analysis of consecutive patients (183 in total, of which 105 were males and 78 females) with gastrointestinal stromal tumour (GIST) was performed. The mean age was 61 years, median age 64 years. The most frequent localization of the tumour was stomach in 74 patients (40.4 %) and the small intestine in 46 patients (25.1 %). Two or more different synchronous or metachronous cancers occurred in 34 (18.6 %) patients with histologically confirmed GIST. Ninety-six patients were treated with imatinib mesylate in palliative setting during the course of their disease. The therapy was finished in 60 patients and 36 patients have been treated so far. The median progression-free survival reached 32.9 months in the group of 96 patients treated with imatinib. The median overall survival in the group of 96 patients treated for metastatic disease reached 77 months. Two-year and 5-year survival was 85.2 % and 63.1 %, respectively. The second-line therapy with sunitinib malate was administered in 37 patients, of which 31 finished and 6 continued in the therapy. The median progression free survival and median survival since the sunitinib therapy initiation reached 8.4 and 22.1 months, respectively (Tab. 2, Fig. 2, Ref. 16).

Czech cancer screening programmes feature a comprehensive multimodal information system which covers all the levels of assessment needed - population-based monitoring (Czech National Cancer Registry), monitoring of results in the diagnostic databases of centres, as well as the quantification of coverage and outputs of primary care according to the administrative data of health care payers. A system of personalised invitations to cancer screening programmes was launched in 2014, based on a stand-alone component of the information system which makes it possible to identify eligible clients in health care payers databases. The system was fully standardised and uniformly implemented in all health insurance companies; its functionalities also involve both continuous and retrospective assessment of the results of personalised invitation. The legislative framework in force will have to be applied and implemented for a more comprehensive and integrated employment of all involved data sources, i.e. cancer registries, screening registries, and administrative data. The system must be able to analyse de-identified individual records on clients participation in screening programmes, and thus to ensure an adequate analysis of performance indicators in compliance with international recommendations.

Background Pulmonary arterial hypertension (PAH) is a severe and progressive disease characterized by increased pulmonary vascular resistance, ultimately leading to right heart failure and death. Epidemiological data from national registries are growing worldwide, but are still unavailable in Eastern Europe. Methods A PAH registry was initiated in January 2007 using a nationwide network of echocardiographic centers and four diagnostic centers that specialize in PAH. All patients aged above 18 years, diagnosed with PAH and monitored between January 2000 and December 2007 were included. Patients diagnosed with PAH between January and December 2007 were classified as incident. The survival analyses were performed up to the end of 2010. Prognostic factors at the time of diagnosis were identified using uni- and multivariable Cox proportional hazard models. Results Overall, 191 patients were included (100 prevalent cases, 91 incident cases). Patients were predominantly female (n = 125) and had a mean age of 51.9 ± 16.9 years. Incident patients were significantly older at the time of diagnosis than prevalent patients (p

Background: Sequential therapy with tyrosine kinase inhibitors (TKIs), sunitinib and sorafenib, is a common treatment choice for patients with advanced/metastatic renal cell carcinoma (mRCC) despite lack of randomised trials. The aim of this retrospective registry-based study was to analyse the outcomes of RCC patients treated with sunitinib-sorafenib or sorafenib-sunitinib sequence. Patients and methods: The Czech database containing information on patients treated for mRCC using targeted agents was used as a source of data for retrospective analysis. There were 138 patients treated with sunitinib-sorafenib sequence and 122 patients treated with sorafenib-sunitinib sequence. Results: Progression-free survival (PFS) was 17.7 months for patients treated with sunitinib-sorafenib sequence and 18.8 months for those receiving sorafenib followed by sunitinib (P = 0.47). Overall survival (OS) at 1 year was 83% [95% confidence interval (CI) 77% to 90%] for patients treated with sunitinib-sorafenib and 84% (95% CI 77% to 91%) for sorafenib-sunitinib patients (P = 0.99). Treatment toxic effects were predictable but a significant proportion of patients (up to 14%-25% for different lines of therapy and used TKI) switched between TKIs or discontinued TKI therapy because of toxicity. Conclusions: In contrast to most of the previously published reports, we have not observed improved PFS or OS for mRCC patients treated with the sorafenib-sunitinib sequence as compared to the sunitinib-sorafenib sequence.

The Czech Society for Oncology has developed an information system which combines the population-based Czech National Cancer Registry with clinical databases in order to cover the main areas of health care assessment - monitoring of the population burden, prediction of the number of cancer patients, diagnostic and treatment results. The presented data demonstrate a high cancer burden within the Czech population - each year there are approximately 8,000 new cases of colorectal cancer, 6,500 new cases of breast cancer, and 1,000 new cases of cervical cancer. And each year, about 4,000 people die from colorectal cancer, around 2,000 women die from breast cancer, and approximately 400 women die from cervical cancer in the Czech Republic. Population-based screening programmes focus on all of the above-mentioned groups of malignant tumours; therefore, it is essential to monitor epidemiological trends in order to assess the screening impact. Despite the high incidence rates of all three cancer types, the trend in mortality rates has been stable or has even decreased in the long term, which has inevitably led to a significant increase in the total prevalence of cancer patients. In 2011, the prevalence of colorectal cancer, breast cancer and cervical cancer amounted to 51,064 people, 67,261 women and 17,398 women, respectively. When compared with the year 2001, there was a 59%, 69% and 25% increase in the prevalence of colorectal cancer, breast cancer, and cervical cancer, respectively. Undoubtedly, taking care of high numbers of cancer patients will continue to require significant financial resources in the near future. As the epidemiological burden is still on the increase, preventive programmes need to be further promoted, including secondary prevention, which is provided through organised screening programmes. Although effective methods exist for timely diagnosis of all three of the above-mentioned cancer types, the epidemiological situation in the Czech Republic is being steadily worsened by a relatively high proportion of primary cancers being diagnosed too late. Each year, more than 50% of new colorectal cancer cases are diagnosed in clinical stage III or higher; in cervical cancer, this proportion is nearly 35%. By contrast, the well-promoted breast cancer screening programme has led to more than 75% of new cases of breast cancer being diagnosed in stages I or II, when the chance of successful treatment is significantly higher.

Abstract 5051 While clinical studies and guidelines provide important data regarding the safety and efficacy of new drugs, their application to daily practice can be limited by the inclusion of selected patient populations. Population-based studies can provide additional insight into the complex process of implementing treatment guidelines in daily practice. The objective of the MyDyS registry was to collect and analyze data regarding the diagnosis and management of patients with myelodysplastic syndrome (MDS) in Slovakia. Material and methods: five clinical centers collected data regarding demographics, staging, history and cytopathology from newly diagnosed patients (pts) with MDS from 2009 to 2011. Patients were classified according to the French American British (FAB) and World Health Organization (WHO) systems and the International Prognostic Scoring System (IPSS). The database allowed online pts registration. Results: one hundred thirty pts were registered to MyDyS in the yrs 2009–2011 and data from 128 pts were analyzed. Male/ female: 53,1%/ 46.9%; average age 64,8 yrs (range 22–89 yrs). The most frequent diagnosis according to FAB classification was RA (53.9%) and RAEB (21.9%), and according to WHO classification RCMD (27,3%) and RAEB II (22,7%). IPSS Low risk was in 16,4% pts, INT-1 in 43%, INT-2 in 19,5% and High risk in 11,7%. The majority of pts were de novo (89,8%). Patients with secondary MDS (10,2%) had a history of malignancy (breast cancer, 23,1%; hematologic malignancy, 2,6% only) and history of combination chemo and radiation therapy in 61,5%. In these pts, bone marrow (BM) was hypercellular in 49,2%, hypocellular in 24,2% of patients. Number of blasts less than 5% in 60,2% patients. Erythroid dysplasia was observed in 88,3%, myeloid dysplasia in 56,3% and dysplasia of megakaryocytes in 71,9% of patients. BM biopsy was performed at diagnosis in 87,5% and reported as hypercellular in 56,6%, with fibrosis in 62,8% and abnormal localization of precursors (ALIP) in 8%. Peripheral cytopenia in 2–3 lineages was observed in 67,2% pts. Growth factor therapy was given to 63 pts and red blood cell transfusions (average 20,7; range 2–80 RBC units) were given to 35 patients. Deferasirox (mostly 1500mg/ d) was given to 25 patients, and serum ferritin level decreased after 8 months in 27,3% pts, after 12 months in 57,4% pts. Chelation therapy was associated with gastrointestinal intolerance in 1 case, and skin reaction in 2 patients. Conclusion: The presented data document the first steps in the complex process of improvement of management of MDS in daily clinical practice in Slovakia. Expansion of the registry is necessary for determination of best practices for discussion with health care authorities and health insurance institutions. Disclosures: No relevant conflicts of interest to declare.

Rare diseases constitute a major burden on public health, mainly due to the high cost of therapy and logistical difficulties (for example, the need to organise a network of designated treatment centres). National and international registries of rare diseases facilitate data collection and analysis for demographic, economic and research purposes. They are also useful for treatment centres and other healthcare providers and pharmaceutical companies developing orphan drugs. We present the HemoRec database, implemented in 2006 in six European countries, as an example of an international registry of inherited bleeding disorders. HemoRec is used in 15 Polish treatment centres and stores data on 1,100 patients with inherited bleeding disorders (amounting to 24.9% of all patients registered in the Polish central registry held at the Institute of Haematology and Blood Transfusion in Warsaw). It can be developed in the future into a national platform of data collection and exchange in the network of Polish, and hopefully also European, haemophilia treatment centres.

Abstract 3651 Introduction: SeveN Bleep (Seven A in Nonhemophilia Bleeding in Pediatrics) is a web-based registry for collecting data on the use of rFVIIa in the treatment of severe and/or life threatening bleeding in children without hemophilia. The registry was endorsed by the Paediatric/Perinatal SSC subcommittee of ISTH. Methods: The registry was established in 2005. During the five years of its existence, 191 cases were recorded, of which 164 (86%) records fulfilled the validation criteria and were eligible for further analyses. For the purpose of analysis, the patients were stratified into two groups: neonates and infants 1 yr old. Statistical methods were used as appropriate. Results: Fifty nine (36%) valid records described the treatment with rFVIIa in neonates and infants, and 105 (64%) in older children. Of these, 27(16%) were for the prevention of severe bleeding. In the rest (84%) of cases, rFVIIa was used to treat severe bleeding. Those 137 cases (42 neonates+infants and 95 older children) were further analysed for the purpose of this report. The median weight in the In those older than 1 year, the median age was 10 years and median weight 30 kg. The reasons for administration of rFVIIa included trauma (45%), “non-trauma” surgery (14%) and bleeding related to malignancy and/or its treatment (11%). Survival rate in this group was 72%. 17% of deaths were related to the underlying hemorrhage treated. There were no thrombotic event or death related to rFVIIa treatment recorded in this group. There was a trend towards using a higher total dose (median 160ug/kg) in patients that died compared to a lower dose (median 120 ug/kg) in those who survived (p=0.078). In addition, those who survived needed lesser number of doses as compared to the deceased patients (median number of doses 1 and 2, respectively; p=0.052). Use of rFVIIa led to a significant decrease in the consumption of blood products in the 24 hour period after rFVIIa administration compared to the 24 hours prior to the use of rFVIIa - packed red cells (280 ml vs. 560 ml; p=0.001), FFP (250 ml vs. 500 ml; p=0.003). There were also significant changes in certain laboratory parameters related to rFVIIa administration also. Estimated blood loss decreased from 30 ml/kg prior to rFVIIa administration to 3 ml/kg after the use of rFVIIa (p=0.002). Conclusion: SevNBleep registry has proven to be a useful international tool for collection of relevant clinical data on the use of rFVIIa. rFVIIa appears to be beneficial in the management of bleeding in the pediatric population. The prevalence of adverse events related to use of rFVIIa was very low, though not absent. To minimize the potential bias related to reporting of SAEs, all major contributing centers has been contacted for further information with regards to consecutive reporting of patients treated with rFVIIa. Disclosures: Off Label Use: rFVIIa use in life threatening bleeding in children.

Background: In recent years, recombinant factor VIIa (rFVIIa) has been used in non-hemophilia bleeding situations (factor VII deficiency, trauma, liver disease, uremia, surgical bleeding, platelet disorders, and intracranial hemorrhage) for achievement of hemostasis. Although, the risk of thrombosis in hemophilia patients with inhibitors receiving rFVIIa is quite low, its use in other clinical situations has been complicated by some reports of thrombotic events. Recently, rFVIIa has been used to treat coagulopathic and/or bleeding neonates with good success. However, the prevalence of thrombotic events in these neonates is completely unknown. This study was initiated to determine the risk of thrombotic events associated with rFVIIa use in neonates. Methods: We reviewed all published literature in neonates receiving rFVIIa. In addition, we reviewed all data submitted to the SeveN Bleep Registry, a database developed by the scientific standardization subcommittee on pediatric and neonatal hemostasis of the International Society on Thrombosis and Haemostasis (ISTH) to record all uses of rFVIIa in pediatric non-hemophilic patients. As the baseline prevalence of thrombosis for bleeding and/or coagulopathic neonates is also unknown, we also reviewed the records of 100 consecutive neonates from a single institution who received fresh frozen plasma (FFP) alone to treat their coagulopathy and/or bleeding. Results: A total of 98 non-hemophilic neonates received rFVIIa. The majority of these neonates received rFVIIa only after failing to achieve hemostasis with standard care (FFP, cryoprecipitate, platelet transfusions). Of those receiving rFVIIa, 7 had a thrombotic event reported. In the control group that received FFP alone, 7 neonates also suffered a thrombotic event. Although the risk of thrombosis in these two groups is similar, neonates receiving rFVIIa tended to have indwelling line related thrombosis, while those receiving FFP tended to have strokes or myocardial insults. Overall the prevalence of thrombotic events in bleeding and/or coagulopathic neonates appears to be 7%, whether or not they received rFVIIa. Conclusions: In this study, the overall prevalence of thrombotic events was similar in the rFVIIa and FFP group. As data for this study was collected in a retrospective manor, and thereby subject to publication and submission bias, a more accurate determination of the prevalence of thrombosis in neonates will require a prospective study.

Background The Czech Breast Cancer Screening Programme (CBCSP) was initiated in September 2002 by establishing a network of accredited centres. The aim of this article is to describe progress in the programme quality over time after the inception of the organised programme. Methods The CBCSP is monitored using an information system consisting of three principal components: 1) the national cancer registry, 2) a screening registry collecting data on all screening examinations, further assessments and final diagnoses at accredited programme centres, and 3) administrative databases of healthcare payers. Key performance indicators from the European Guidelines have been adopted for continuous monitoring. Results Breast cancer incidence in the Czech Republic has steadily been increasing, however with a growing proportion of less advanced stages. The mortality rate has recently stabilised. The screening registry includes 2,083,285 records on screening episodes between 2002 and 2008. In 2007-2008, 51% of eligible women aged 45-69 were screened. In 2008, the detection rates were 6.1 and 3.7 per 1,000 women in initial and subsequent screening respectively. Corresponding recall rates are 3.9% and 2.2%, however, it is necessary to pay attention to further assessment performed during the screening visits. Benign to malignant open biopsy ratio was 0.1. Of invasive cases detected in screening, 35.6% was less than 10 mm in diameter. Values of early performance indicators, as measured by both crude and standardized estimates, are generally improving and fulfil desirable targets set by European Guidelines. Conclusions Mammography screening in the Czech Republic underwent successful transformation from opportunistic prevention to an organised programme. Values of early indicators confirm continuous improvement in different aspects of process quality. Further stimulation of participation through invitation system is necessary to exploit the full potential of screening mammography at the population level.