Epidemiological Trends for Childhood and Adolescent Cancers in the Period 1994-2016 in the Czech Republic.

BACKGROUND: Our study aimed to evaluate incidence and mortality trends for childhood and adolescent cancers in the period 1994-2016 in the Czech Republic. MATERIAL AND METHODS: Data on childhood cancers, which are recorded in the Czech National Cancer Registry, were validated using a clinical database of childhood cancer patients and combined with data from the National Register of Hospitalised Patients and with data from death certificates. These validated data were used to establish cancer incidence. Data from death certificates were used to evaluate long-term trends in mortality. Incidence and mortality trends were assessed by the average annual percentage change. RESULTS: The age-standardised incidence trend for childhood cancers (i.e. those diagnosed in patients aged 0-19 years) showed a statistically significant slight long-term increase in the number of new cases, +0.5% annually on average (p < 0.01), more specifically an increase of +0.6% in girls and a statistically insignificant decrease of 0.1% in boys. In children aged 0-14 years, other malignant epithelial neoplasms and malignant melanomas showed the largest statistically significant average annual increase in incidence (+4.9%; p < 0.01), followed by central nervous system neoplasms (+1.3%; p < 0.05). Lymphomas, by contrast, showed a statistically significant average annual decrease in incidence in children aged 0-14 years (2.1%; p < 0.01). In adolescents aged 15-19 years, other malignant epithelial neoplasms and malignant melanomas also showed a statistically significant average annual increase in incidence (+5.2%; p < 0.01), followed by central nervous system neoplasms (+1.5%; p < 0.05). Mortality trends showed a statistically significant long-term decrease: on average, 5.1% annually in children aged 0-14 years (p < 0.01), and 3.7% annually in adolescents aged 15-19 years (p < 0.01). CONCLUSION: Available data make it possible to analyse long-term trends in childhood cancer incidence and mortality.

Trends in incidence of childhood cancers in the Czech Republic: population- based analysis of national registries (1994-2014).

The purpose of this study is to summarize incidence and trends in the pediatric cancer burden in the Czech Republic over the period 1994-2014. The recently established Childhood Cancer Registry was combined with retrospective data from the Czech National Cancer Registry to analyze the annual patterns of incidence and long-term trends of pediatric cancer patients aged 0-14 years diagnosed between 1994 and 2014. Malignancies were classified according to the International Classification of Childhood Cancer. The distribution of incidence was stratified according to gender, age at diagnosis, type of cancer and geographic area. Annual age-standardized rates were adjusted using the world standard population. Changes over time were quantified as the average annual percentage change. This analysis comprised records of 5,605 children diagnosed with cancer within the period 1994-2014, annually 267 records on average; the overall age-standardized average annual incidence rate was 169 cases per million. Boys were affected more frequently than girls: the M/F crude incidence ratio was 1.2:1. The highest incidence rates were observed for ICCC groups I (27.8%), III (21.8%), II (12.4%) and IV (7.8%); other groups formed 30.2%. There are significant differences in the geographic distribution of incidence between regions. A borderline statistically significant increase (0.6%) in the overall average annual percentage change was detected between 1994 and 2014 (95% CI: 0.01 to 1.12; p = 0.05). This study provides reliable recent information on trends in the incidence of childhood cancers in the Czech Republic.

[State and development of background information for the evaluation of Czech cancer screening programmes]. / Stav a vývoj informacní základny pro hodnocení onkologických screeningových programu v Ceské republice.

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.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Performance indicators in screening programmes]. / Indikátory kvality screeningových programu

Breast, colorectal and cervical cancer screening programmes make it possible to decrease the population mortality rates of these diseases. How-ever, complex standards of the quality of care must be introduced and followed in order to maintain a favourable ratio between the benefits and risks arising from population-wide screening programmes. Such programmes should be organized and population-based, ensuring that quality control is performed at all levels. This review introduces the system of quality control in the Czech cancer screening programmes, and provides specific examples of performance indicators that are usable and/ or being used in these programmes. Cancer screening programmes in the Czech Republic are equipped with a comprehensive information background which involves monitoring of the cancer burden in the population, monitoring of the screening process based on clinical data, and monitoring of the screening process based on administrative data. In particular, the specific performance indicators describe the success rate of take up of the target population, ability of the screening test to reveal (sensitivity) or to exclude (specificity) the screened condition, correct employment of subsequent diagnostic methods or treatment of detected cancers or precancerous lesions where applicable. In the Czech breast cancer screening programme, these indicators are routinely used in order to monitor the individual centres; in both colorectal and cervical cancer screening programmes, these indicators are used to monitor the entire programme, whereas the system of quality control for individual centres is under continuous development. A project of personalized invitations was launched in 2014, and its results are regularly evaluated in cooperation with the Czech National Reference Centre and the Ministry of Health of the Czech Republic.

[Serious sepsis treatment in intensive care departments in the Czech Republic -  EPOSS Project pilot results]. / Lécba tezké sepse na pracovistích intenzivní péce v Ceské republice -  pilotní výsledky projektu EPOSS.

INTRODUCTION: Severe sepsis is still associated with significant morbidity and mortality, which is however different, as well as its management, depending on the region. What is the situation in the Czech Republic and what is the character of patients with severe sepsis is currently not known. The aim of the project is to describe the processes of care, outcome and characteristics of patients with severe sepsis admitted to the intensive care department of the Czech Republic. METHODS: This is a multicentre and observational project with retrospective enrollment of patients who meet the criteria for severe sepsis before or within 24 hours after admission to selected intensive care units (ICU EPOSS). RESULTS: 394 patients were analyzed. Median age at admission was 66 (56- 76) years, males predominated (58.9%) and the median APACHE II score on admission was 25 (19- 32). Patients were predominantly medical (56.9%) and most were secondary admitted from other ICU (53.6%). Meeting the criteria of severe sepsis was most frequently within the period (± 4 hours) of admission the EPOSS ICU (77.6%). Median total fluid intake during the first 24 hours was 6,680 (4,840- 9,450) ml. Most patients required mechanical ventilation (58.4%). Compliance with the resuscitation bundle of severe sepsis in our group was very good and was associated with lower mortality of patients. Most frequently, the EPOSS ICU length of stay (LOS) was 7 (3- 15) days and median hospital LOS was 13 (8- 28) days. Hospital mortality in our cohort was 35.8%. CONCLUSION: Introducing the project, which in its first stage obtained valuable and internationally comparable data about patients with severe sepsis admitted to the involved ICU in the Czech Republic.

[Metastatic renal cell carcinoma treated with everolimus--data from the RENIS Clinical Registry]. / Výsledky terapie metastatického renálního karcinomu lékem everolimus--analýza udaju z klinického registru RENIS.

Everolimus is an oral mTOR kinase inhibitor approved for the treatment of patients with metastatic renal cell carcinoma (mRCC) progressing during or after treatment with vascular endothelial growth factor (VEGF)-targeted agents. Using the national RENIS clinical registry, we have retrospectively analysed outcomes of patients treated for mRCC with everolimus. A total of 78 patients were evaluable. Median progression-free survival from the start of everolimus therapy was 7 months (95% confidence interval 2-12 months). Partial response or stable disease was achieved in 69% of patients. Treatment toxicity was predictable and serious adverse events occurred in only 6% of patients the most common being respiratory toxicity. Everolimus therapy provides significant clinical benefit for heavily pretreated mRCC patients after failure of VEGF-targeted therapy.

[Czech Ophthalmologic Society's data collecting system for the monitoring and evaluating of the exsudative age-related macular degeneration treatment--the nation-wide project "AMADEUS"]. / Informacní zázemí Ceské oftalmologické spolecnosti CLS JEP pro monitoring a hodnocení lécby vlhké formy vekem podmínené makulárni degenerace-národní projekt AMADEUS.

The Czech Ophthalmologic Society (member of the Czech Medical Society of Jan Evangelista Purkyne) in collaboration with the Institute of Biostatistics and Analysis of the Masaryk University in Brno established a nation-wide information system for the follow-up of the epidemiology and treatment of the exsudative age-related macular degeneration (ARMD). The project named AMADEUS is a multi-centric, non-invasive, observation prospective study with the aim to improve the patients' treatment and to unify the criteria for the follow-up of the ARMD in the real clinical practice in the Czech Republic. The basic instrument of the whole project is a clinical register collecting parametric data from 9 specialized centers. Especially the project monitors the photodynamic therapy with Verteporfyrine (Visudyne) and treatment by anti-VEGF agents, or Pegaptanib (Macugen) and Ranibizumab (Lucentis). The project's protocol is trying to collect representative data about ARMD diagnosis and treatment; during regularly controls, the efficacy and safety of the treatment are followed-up.The data collecting does not influence the treatment strategy or the availability of chosen treatment for the patient. Since October 2008 until the end of the year 2009, the registry collected complex information about more than 1402 newly treated ARMD patients; out of them, in 582 cases the one-year follow-up period was regularly terminated. The available data shows well-considered indication of drugs indications by the doctors; the treated patients fulfill the indications criteria set by the scientific society. According to the data from the registry, in some treating centers the application schedule is not followed-up in some drugs (especially Pegaptanib); there is the possibility to improve the treatment. All the clinical centers participating in the AMADEUS registry will continue in the data collecting, which after a longer period of time will facilitate further treatment optimization and eliminating of the established imperfections. Further information about the project may be found at the web site: www.amadeus.registry.cz.

A whole population study of gastrointestinal stromal tumors in the Czech Republic and Slovakia.

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.

Internet-based system for anti-tumor chemotherapy evaluation.

The Internet-based system DIOS addresses the issues of anti-tumor chemotherapy and its evaluation. The repository of chemotherapeutic regimens (CHRs) stored in XML structured format constitutes the core of the system. Several applications have been created based on this repository, in order to allow users to browse current CHRs and procedures of planning and evaluation of chemotherapy based on the dose intensity concept. This freely available system uses technology based on the XML standard and XSLT transformations.

Multivariate analysis of risk factors for testicular cancer: a hospital-based case-control study in the Czech Republic.

Growing incidence of testicular cancer around the world stimulates research attempting to explain the trends. This study quantified the contribution of different types of potential risk factors for testicular germ-cell cancer (TGCC) with differentiation between seminoma and non-seminoma. A standardized questionnaire containing demographic data, pre- and perinatal factors, social, lifestyle and occupational parameters was prepared. The data file consists of n = 356 TGCCs (seminoma: n = 195; non-seminoma: n = 161) and n = 317 controls, frequency matched on age to cases. The following factors were significantly associated with the risk of TGCCs in univariate analyses (ORs): atrophic testis (5.3), smoking over 12 pack-yr (4.9), cryptorchidism (2.9), testicular trauma (2.0), birth weight under 3,000 g (1.6), low degree of education (3.0) in correlation with manual occupation (2.3) and finally, overall familial cancer history (1.5) and familial history of breast (1.8) and prostate cancer (3.9). On the other hand, maternal age over 20 yr (OR < 0.4) and moderate recreational sport activity (OR = 0.5) significantly reduced the risk of TGCCs. A significant risk was associated with cryptorchidism (OR = 2.9; 95% CI = 1.5 - 5.9) where orchidopexy was delayed after 5 yr of age (OR = 5.2; 95% CI = 1.5-18.1). Delayed orchidopexy was associated namely with the risk of seminomas (OR = 7.5; 95% CI = 2.1-26.7). Only some of the variables were retained in multivariate model for TGCCs as well as for histological subtypes (multivariate adjusted OR for all TGCCs): atrophic testis (5.9), family history of prostate cancer (4.8), cryptorchidism (3.8) and interaction term 'low degree of education & manual occupation' (3.0). Familial history of breast cancer elevated risk of TGCCs and of seminomas (OR: 2.01 - 2.18). Birth weight under 3,000 g was retained in a multivariate model for TGCCs with a borderline significance (OR = 1.67). We could not rule out any type of risk factors, as each one was significantly represented in the final multivariate models. Familial cancer history remained to be an influential risk factor, altogether with some lifestyle and occupational parameters. This suggests that both environmental exposures and genetic inheritance can play role in the moderation of the risk of TGCC.

[Acute situation in the National Program of Breast Cancer Screening in the Czech Republic]. / Akutní stav národního programu skríninku rakoviny prsu v Ceské republice.

Czech National Breast Cancer Screening Program started in September 2002. Currently, a total of 59 accredited screening centres are involved in the program. Central data management and statistical processing of the data is performed. During the period of July 2003-December 2005 a total of 646,056 women were screened and 2,926 breast cancer cases were detected. A total of 2666 (91.1 %) cancer cases were invasive. Of these, 855 (32.1 %) were < or = 10 mm in size and 1624 (60.9 %) were node negative. A high rate of detection of early stages of the disease is the main objective of the screening process and a good indicator of long-term decrease in mortality rates. The central system of data management is based on annual data analysis. This system is in line with international standards for such systems.

Web portal for management of bioindication methods and ecotoxicological tests in ecological risk assessment.

The objective of this article is to inform about efforts to design and implement a data model that can parametrically describe and store information about a wide range of ecotoxicological tests and bioindication methods used in Ecological Risk Assessment (EcoRA). At the same time it describes comprehensive web-based portal built on this model that can be used to quickly find relevant biological assays (ecotoxicological biotests) for given situation and therefore support the decision-making process in EcoRA. The model structure, features of the corresponding website and its current content is described in detail and proposed development and possible collaboration is outlined. The portal (DATEST) is located at http://projects.cba.muni.cz/datest. The aim of this work is to complement existing EcoRA decision-support tools with a web-based engine for storing and searching biological tests and methods used in EcoRA as there is currently no similar informational source available on the Internet.

Breast cancer and neoadjuvant therapy: any predictive marker?

The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. However, the effect of cytotoxic treatment cannot be predicted on individually specific basis, then identification of tumor characteristics associated with tumor therapeutic response and outcome is then of great clinical interest. We studied 141 patients at Masaryk Memorial Cancer Institute, who received neoadjuvant chemotherapy and/or chemotherapy + radiotherapy (CHT/CHT+RT) between 1994-2002. Tumor samples were taken prior to and after neoadjuvant therapy. We quantified the response to therapy pathologically and determined histological and molecular tumor characteristics (steroid receptors, CEA, Ca 15-3). In addition to therapeutic response as immediate outcome, event free survival (EFS) was examined as more complex primary end-point of the study. Complete remission (CR) has been achieved in 6.5%, partial remission (PR) in 49.6%, stable disease (SD) in 26.2% and progression disease (PD) in 17.7% patients. Patients were divided into two groups according to the result of neoadjuvant therapy--responders (CR+PR+SD, who successfully underwent surgery), and risk group (patients with SD or PD, who could not undergo surgery). Responders to neoadjuvant CHT/CHT+RT regimens reached statistically significant better EFS than non-responders, low tumor size (T2) and stage (II) categories were confirmed as additional predictive factors not only for EFS but for therapeutic response as well. The study primarily examined predictive power of tumor markers as CEA, Ca 15-3, and steroid receptors (ER/PR) and searched for their role in the prospective evaluation of neoadjuvant therapy. We evaluated these factors as potential predictors of EFS, independent in predictive power on therapeutic response to neoadjuvant therapy. Diagnostically valuable cut off points were proposed in ROC analysis for all these markers. Responders to the neoadjuvant therapy with Ca 15-3 <23.0 kU/l, CEA <5.0 mg/l, estrogen receptors (ER) >5.0 fmol/mg or both estrogen /progesterone receptors (ER/PR) positive had statistically significantly better EFS in comparison to patients with Ca 15-3 >23.0 kU/l, CEA >5.0 mg/l, ER <5.0 fmol/mg, or other cases than patients double positive in ER/PR. Marker Ca 15-3 revealed significant predictive power even within the group of non- responders, these patients with Ca 15-3 <23.0 kU/l had better EFS as compared to patients with Ca 15-3 >23.0 kU/l. Tumor size and low stage proved predictive value for immediate response to neoadjuvant therapy. Risk parameters for neoadjuvant therapy were T4, stage III, namely if RT was necessary. Therapeutic response to neoadjuvant therapy was independent on investigated molecular parameters, but there was strong predictive association of Ca 15-3, CEA and ER/PR receptors with event free survival development. Diagnostically valuable cut-off points were proposed and validated for sensitivity and specificity in ROC analysis.