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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

Background and Aim: From October 2013 there is a possibility to treat patients with NSCLC and with activated epidermal growth factor receptor (EGFR) mutations with three TKI in the Czech Republic. We have tried to find differences among patient groups treated with single TKI in 1st line of treatment. Patients and methods: Only patients with EGFR mutation and in which 1st line treatment started in October 2013 until October 2017 were included in analysis. We analysed 347 patients (gefitinib - 164 patients, afatinib - 130 patients, erlotinib - 53 patients). Results: Between these three groups of patients there was no statistically significant difference in sex (p=0.988), in smoking habits (p=0.549), in type of EGFR mutation (p=0.200), in adenocarcinoma proportion (p=0.256). There was statistically significant difference according to age (p=0.001), PS ( Conclusion: We have not found any important difference in basic characteristic of patients treated in 1st line treatment with TKI (sex, smoking, histology and type of EGFR mutation) except for the age – patients treated with afatinib were younger. We have not found any important difference in response to treatment, in disease control and OS. We found a significant difference in PS segmentation, in occurrence of adverse events and PFS.

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

We present data collected in HemoRec, an Internet-based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand's disease is largely under-registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.

Effective planning of clinical trials requires an appropriate number of patients who fulfil given inclusion criteria. In the case of so called “orphan” diseases, such as Duchenne and Becker muscular dystrophy (DMD/BMD), the number of suitable patients within one country is usually limited. We developed a detailed registry of Czech and Slovak DMD/BMD patients which may contribute to cooperation on the European level. The registry uses internet and database technologies with a multilevel architecture. Patients may view their own data. As of May 2008, 163 patients have been registered in the database. The registry provides a detailed phenotypic and genotypic description of patients. The main purpose of such a registry is the time-effective recruitment of eligible patients for a clinical trial or therapy and may allow the anticipation of possible future effects of appropriate therapy on individual patients. The importance of the DMD/BMD patient registries has recently also been rising with new clinical trials focused on mutation-specific approaches. Other outputs include assessment of epidemiology, phenotype and genotype relationships, or standards of care.

Due to problems with identification and an incomplete understanding on the gastrointestinal stromal tumors (GIST) before 2001, there has been a lack of comprehensive long-term population-based studies on GIST epidemiology at present date. We used data from the online registry of Czech and Slovak GIST patients (http://gist.registry.cz/), which has been compiled and maintained since 2006 and involves patients diagnosed from the year 2000. 278 patients were included in this study. Most of the tumors fell into the high-risk category (58.7%), followed by the intermediate (21.4%), low (16.6%) and very low (3.3%) categories. Locations other than the small intestine and stomach had significantly higher contribution of high-risk tumors. The median time of overall survival was 93.2 months, 5-year relative survival was 78.3% overall, 71.9% for patients with high-risk tumors, 91.1% for intermediate patients, and 91.9% for patients from the low- and very low-risk category. The annual crude incidence between the years 2001-2005 was 0.52 cases per 100,000 inhabitants. The annual European ASR and World ASR were 0.44 and 0.31 per 100,000 inhabitants, respectively. Presented data generally correspond to the whole-population studies recently published, including actual data on epidemiology, clinical characteristics, and survival of patients. The registry helps in improving GIST diagnostics, knowledge about the properties and behaviour of tumors, communication among physicians, and, last but not least, therapeutical options and results.

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.

Identifying haemophilia patients with inhibitors for clinical trials is difficult due to the limited number of patients available. Registries are therefore being established as an additional means of data collection. The aim of this study was to investigate the effect of different recombinant activated factor VII (rFVIIa; NovoSeven dose ranges and dosing schedules on the incidence of re-bleeding in haemophilia patients with inhibitors. In this retrospective, uncontrolled study, data on the bleeding patterns of adult haemophilia patients with high responding inhibitors were analysed. Only data from the Czech Republic, obtained by the HemoRec registry, were used. This study analysed 'real-life' clinical data and focused on the collection of the same parameters in different patients: time from bleeding onset to first injection, effect of first injection, number of re-bleedings, total number of injections and total amount of haemostatic drug used. Fifteen patients met the inclusion criteria and were included into the study (128 bleeding episodes). Patients treated within 2 h of bleeding onset experienced less re-bleeding than patients treated after 2 h of bleeding onset (5.2% vs. 13.7%, respectively). In addition, patients who were treated after 2 h of bleeding onset experienced fewer re-bleedings when high-dose rFVIIa was used (15.8% and 0%;120 microg kg(-1) and250 microg kg(-1), respectively). Initial high-dose rFVIIa was also associated with a decline in total rFVIIa consumption. This registry has provided a unique insight into the bleeding patterns of inhibitor patients, highlighting the importance of early treatment initiation and appropriate starting dose.

The patient registries belong to the core activities which can help us in planning of the effective health care, assessing standards of diagnosis and care, and answer the questions concerning on epidemiologic data. Besides of the local hospital-based databases and registries we can find in Czech Republic four national registries of hereditary neuromuscular disorders associated under unique name: ReaDy (registry of muscular dystrophy). Four registries are currently running: Duchenne/Becker muscular dystrophy (DMD/BMD), spinal muscular atrophy (SMA), myotonic disorders (MD), and facioscapulohumeral muscular dystrophy (FSHD). Each registry is independent and has its own curator. The registries are under the supervision of Czech neuromuscular society. The technology, the data collection, the storage, the backup, and analyses are provided by the Institute of Biostatistics and Analyses, Masaryk University, Brno, CR. On-line data collection is based on a TRIALDB system developed on Yale University, Connecticut, USA, which is widely used for this purpose. For each patient is generated a unique ID; all data transfer is encrypted and the system is designed to prevent their unauthorized use during data transfer. Laws and regulations in CR require having an informed consent from all patients whose data are used in the registry. All claims for personal data protection were met. Data are stored on the central server on Masaryk University in Brno in Oracle 9i database. Since 2011 to the March 2014 796 Czech patients were collected: 370 DM, 277 DMD/BMD, 89 FSHD, and 60 SMA. The majority (76%) of all records are from two centers (Prague and Brno). The average annual increase during last three years is 96 patients. The biggest acquisition reveal patients with myotonic disorders (about 45 per year), the smallest growth has the registry FSHD with approx. 11 patients per annum.

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.

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.