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1.
Leukemia ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31431735

RESUMO

We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.6 to 42%. Nine translocation breakpoints were detected. Genes involved in JAK/STAT, NFkB and PI3K signaling and antigen presentation were most frequently affected. SOCS1 variants, mainly deletions, were found in most circulating tumor (ct) DNAs, and seven of the nine translocation breakpoints involved SOCS1. Analysis of VH-DH-JH rearrangements revealed an origin of PHL HRS cells from partially selected germinal center B cells. Amounts of pretherapy ctDNA were correlated with metabolic tumor volumes. Furthermore, in all ccfDNA samples of 43 patients with early response assessment quantitative qPET < 3, indicative of a favorable clinical course, ctDNA was not detectable. In contrast, in five of six patients with qPET > 3, indicative of an unfavorable clinical course, ctDNA remained detectable. ccfDNA analysis of PHL is thus a suitable approach to determine pathogenic mechanisms and monitor therapy response.

2.
Eur J Cancer ; 116: 13-20, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31163337

RESUMO

RATIONALE: The impact of biopsying Wilms tumour (WT) at diagnosis on assigning the tumour stage and recommended treatment remains controversial. To address this important question, we analysed the potential association of all types of biopsy with local recurrence in patients treated in the SIOP WT 2001 trial, where needle biopsy was permitted without 'upstaging' the tumour to stage III. Only open biopsy required treatment as stage III. METHODS: Among 2971 patients with unilateral WT (stages I-IV), 420 relapsed (139 local). Risk factors for recurrence were analysed by Cox proportional hazard methods. RESULTS: Biopsy was performed in 969 of 2971 (33%) patients (64% cutting needle, 30% fine needle aspiration [FNA] and 6% open biopsy). Biopsied patients were older, with larger tumours and a greater proportion with high-risk histology. In multivariate analysis that included all factors associated with local recurrence in univariate analysis, only high-risk histology (hazard ratio [HR] = 2.32; 95% confidence interval [CI]: 1.58-3.42, p=<0.0001), age≥2 years (HR = 2.24; 95% CI: 1.22-4.09, p = 0.01) and preoperative tumour volume (HR = 1.07 per 100 ml; 95% CI: 1.02-1.12, p = 0.01) were significant. The HR for the association of local recurrence and event-free and overall survival with biopsy was not significant (HR = 1.4; 95% CI: 0.9-2.17, p = 0.13; HR = 1.1; 95% CI: 0.85-1.42, p = 0.46 and HR = 1.13; 95% CI: 0.79-1.62, p = 0.51, respectively). These results were not materially different whether FNA or open biopsy were included in the biopsy group or not. CONCLUSIONS: This post hoc analysis provides some reassurance that needle biopsy is not an independent adverse factor for either local recurrence or survival after adjustment for all relevant risk factors. Needle biopsy should not be an automatic criterion to 'upstage' WT.

4.
Bioinformatics ; 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31038669

RESUMO

MOTIVATION: Breast cancer is the second leading cause of cancer death among women. Tumors, even of the same histopathological subtype, exhibit a high genotypic diversity that impedes therapy stratification and that hence must be accounted for in the treatment decision-making process. RESULTS: Here, we present ClinOmicsTrailbc, a comprehensive visual analytics tool for breast cancer decision support that provides a holistic assessment of standard-of-care targeted drugs, candidates for drug repositioning, and immunotherapeutic approaches. To this end, our tool analyzes and visualizes clinical markers and (epi-)genomics and transcriptomics datasets to identify and evaluate the tumor's main driver mutations, the tumor mutational burden, activity patterns of core cancer-relevant pathways, drug-specific biomarkers, the status of molecular drug targets, and pharmacogenomic influences. In order to demonstrate ClinOmicsTrailbc's rich functionality, we present three case studies highlighting various ways in which ClinOmicsTrailbc can support breast cancer precision medicine. ClinOmicsTrailbc is a powerful integrated visual analytics tool for breast cancer research in general and for therapy stratification in particular, assisting oncologists to find the best possible treatment options for their breast cancer patients based on actionable, evidence-based results. AVAILABILITY: ClinOmicsTrailbc can be freely accessed at https://clinomicstrail.bioinf.uni-sb.de. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

6.
Anticancer Res ; 39(4): 2043-2051, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952748

RESUMO

BACKGROUND/AIM: The need for more effective treatment modalities that can improve the clinical outcome of patients with glioblastoma multiforme remains imperative. Dendritic cell vaccination is a fast-developing treatment modality, currently under exploration. Functional immune cell subpopulations may play a role in the final outcome. MATERIALS AND METHODS: Data from 101 patients drawn from the HGG-2010 trial, including baseline patient characteristics and fluorescence-activated cell sorting of immune cell subpopulations, were analyzed by statistical and machine-learning methods. RESULTS: The analysis revealed strong correlations between immune profiles and overall survival, when the extent of resection and the vaccination schedule were used as stratification variables. CONCLUSION: A systematic, in silico workflow detecting strong and statistically significant correlations between overall survival and immune profile-derived quantities obtained at the start of dendritic cell vaccination was devised. The derived correlations could serve as a basis for the identification of prognostic markers discriminating between potential long- and short-term survivors of patients with glioblastoma multiforme.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Células Dendríticas/imunologia , Glioblastoma/imunologia , Glioblastoma/terapia , Temozolomida/uso terapêutico , Adulto , Idoso , Terapia Combinada , Feminino , Citometria de Fluxo , Humanos , Imunoterapia , Leucaférese , Masculino , Pessoa de Meia-Idade , Fenótipo , Resultado do Tratamento , Vacinação
7.
Int J Cancer ; 145(4): 941-951, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30694527

RESUMO

Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss-of-function effect of the mutations identified. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial-type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH.

8.
Nat Rev Urol ; 15(11): 693-701, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30310143

RESUMO

On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP-RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP-RTSG pathology panel.

9.
Pediatr Hematol Oncol ; : 1-7, 2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30260265

RESUMO

Although the fate of nephrogenic rests varies, they are known to be precursors of Wilms tumour. Thus, nephrogenic rests require adequate treatment to prevent malignant transformation. We added 13-cis retinoic acid to the standard chemotherapy with vincristine and actinomycin-D in two patients with bilateral nephrogenic rests/nephroblastomatosis. Patient 1 also had a history of Wilms tumour. 46 (patient 1) and 81 (patient 2) months after end of treatment, both patients show stable conditions with no signs of relapse or progressive disease. Our observation supports further investigation of retinoic acid in patients with nephrogenic rests and nephroblastomatosis.

10.
Ecancermedicalscience ; 12: 848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30079110

RESUMO

Clinical decision support systems can play a crucial role in healthcare delivery as they promise to improve health outcomes and patient safety, reduce medical errors and costs and contribute to patient satisfaction. Used in an optimal way, they increase the quality of healthcare by proposing the right information and intervention to the right person at the right time in the healthcare delivery process. This paper reports on a specific approach to integrated clinical decision support and patient guidance in the cancer domain as proposed by the H2020 iManageCancer project. This project aims at facilitating efficient self-management and management of cancer according to the latest available clinical knowledge and the local healthcare delivery model, supporting patients and their healthcare providers in making informed decisions on treatment choices and in managing the side effects of their therapy. The iManageCancer platform is a comprehensive platform of interconnected mobile tools to empower cancer patients and to support them in the management of their disease in collaboration with their doctors. The backbone of the iManageCancer platform comprises a personal health record and the central decision support unit (CDSU). The latter offers dedicated services to the end users in combination with the apps iManageMyHealth and iSupportMyPatients. The CDSU itself is composed of the so-called Care Flow Engine (CFE) and the model repository framework (MRF). The CFE executes personalised and workflow oriented formal disease management diagrams (Care Flows). In decision points of such a Care Flow, rules that operate on actual health information of the patient decide on the treatment path that the system follows. Alternatively, the system can also invoke a predictive model of the MRF to proceed with the best treatment path in the diagram. Care Flow diagrams are designed by clinical experts with a specific graphical tool that also deploys these diagrams as executable workflows in the CFE following the Business Process Model and Notation (BPMN) standard. They are exposed as services that patients or their doctors can use in their apps in order to manage certain aspects of the cancer disease like pain, fatigue or the monitoring of chemotherapies at home. The mHealth platform for cancer patients is currently being assessed in clinical pilots in Italy and Germany and in several end-user workshops.

11.
Ecancermedicalscience ; 12: 853, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30079115

RESUMO

Developments in information and communication technology have changed the way healthcare processes are experienced by both patients and healthcare professionals: more and more services are now available through computers and mobile devices. Smartphones are becoming useful tools for managing one's health, and today, there are many available apps meant to increase self-management, empowerment and quality of life. However, there are concerns about the implications of using mHealth and apps: data protection issues, concerns about sharing information online, and the patients' capacity for discerning effective and valid apps from useless ones. The new General Data Protection Regulation has been introduced in order to give uniformity to data protection regulations among European countries but shared guidelines for mHealth are yet to develop. A unified perspective across Europe would increase the control over mHealth exploitation, making it possible to think of mHealth as effective and standard tools for future medical practice.

12.
Int J Cancer ; 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30155889

RESUMO

Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.

13.
Orphanet J Rare Dis ; 13(1): 117, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30016967

RESUMO

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a rare multisystem disorder. In 2012 diagnostic criteria for TSC were revised. However, data on the incidence of TSC are limited. METHODS: Prospective, national surveillance study in Germany over a 2-year-period (03/2015-02/2017) using current revised criteria for TSC. Patients up to the age of 18 years with a new diagnosis of definite or possible TSC (clinical and/or genetic) were included. The aims of this study were 1) to generate up-to-date data on the incidence of definite or possible TSC, 2) to assess age at first diagnosis, and 3) to compare these data with previous epidemiologic data. RESULTS: In total, 86 patients met inclusion criteria (definite or possible TSC) with a median age at diagnosis of 6 months (range: 5 months before birth - 197 months of age). Among patients identified with features of TSC, 73.3% met criteria for definite diagnosis (median age: 7 months) and 26.7% met criteria for a possible diagnosis (median age: 3 months). 55.8% of patients were male. When excluding prenatally diagnosed patients, median age at diagnosis was 11 months with a range of 0 to 197 months. The 3 most common clinical features at diagnosis of TSC were central nervous system involvement in 73.3% patients (of these 95.2% experienced seizures), cutaneous involvement in 58.1% patients (with the most common lesion being hypomelanotic macules in 92%) and cardiac rhabdomyoma in half of the patients. Cardiac rhabdomyoma were detected by prenatal ultrasonography in 22.1% of patients. The presence of cardiac rhabdomyoma was associated with cardiac arrhythmias in 25.6% (about 13% of all diagnosed patients) in our cohort. The overall prevalence of seizure disorders was 69.8%. The annual incidence rate of TSC is estimated at a minimum of 1:17.785 live births. However correcting for underreporting, the estimated incidence rate of definite or possible TSC is approximately 1:6.760-1:13.520 live births in Germany. CONCLUSIONS: This is the first study that assessed prospectively the incidence rate of TSC in children and adolescents using the updated diagnostic criteria of 2012. This prospective surveillance study demonstrates a low age at first diagnosis (median: 6 months), likely due to antenatal detection of cardiac rhabdomyoma. Early diagnosis bears the potential for implementing effective therapies at an earlier stage.

14.
Lancet Oncol ; 19(8): 1072-1081, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29960848

RESUMO

BACKGROUND: Wilms' tumour is the most common renal cancer in childhood and about 15% of patients will relapse. There is scarce evidence about optimal surveillance schedules and methods for detection of tumour relapse after therapy. METHODS: The Renal Tumour Study Group-International Society of Paediatric Oncology (RTSG-SIOP) Wilms' tumour 2001 trial and study is an international, multicentre, prospective registration, biological study with an embedded randomised clinical trial for children with renal tumours aged between 6 months and 18 years. The study covers 243 different centres in 27 countries grouped into five consortia. The current protocol of SIOP surveillance for Wilms' tumour recommends that abdominal ultrasound and chest x-ray should be done every 3 months for the first 2 years after treatment and be repeated every 4-6 months in the third and fourth year and annually in the fifth year. In this retrospective cohort study of the protocol database, we analysed data from participating institutions on timing, anatomical site, and mode of detection of all first relapses of Wilms' tumour. The primary outcomes were how relapse of Wilms' tumour was detected (ie, at or between scheduled surveillance and with or without clinical symptoms, scan modality, and physical examination) and to estimate the number of scans needed to capture one subclinical relapse. The RTSG-SIOP study is registered with Eudra-CT, number 2007-004591-39. FINDINGS: Between June 26, 2001, and May 8, 2015, of 4271 eligible patients in the 2001 RTSG-SIOP Wilms' tumour database, 538 (13%) relapsed. Median follow-up from surgery was 62 months (IQR 32-93). The method used to detect relapse was registered for 410 (76%) of 538 relapses. Planned surveillance imaging captured 289 (70%) of these 410 relapses. The primary imaging modality used to detect relapse was reported for 251 patients, among which relapse was identified by abdominal ultrasound (80 [32%] patients), chest x-ray (78 [31%]), CT scan of the chest (64 [25%]) or abdomen (20 [8%]), and abdominal MRI (nine [4%]). 279 (68%) of 410 relapses were not detectable by physical examination and 261 (64%) patients did not have clinical symptoms at relapse. The estimated number of scans needed to detect one subclinical relapse during the first 2 years after nephrectomy was 112 (95% CI 106-119) and, for 2-5 years after nephrectomy, 500 (416-588). INTERPRETATION: Planned surveillance imaging captured more than two-thirds of predominantly asymptomatic relapses of Wilms' tumours, with most detected by abdominal ultrasound, chest x-ray, or chest CT scan. Beyond 2 years post-nephrectomy, a substantial number of surveillance scans are needed to capture one relapse, which places a burden on families and health-care systems. FUNDING: Great Ormond Street Hospital Children's Charity, the European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment, The Danish Childhood Cancer Foundation, Cancer Research UK, the UK National Cancer Research Network and Children's Cancer and Leukaemia Group, Société Française des Cancers de l'Enfant and Association Leon Berard Enfant Cancéreux and Enfant et Santé, Gesellschaft für Pädiatrische Onkologie und Hämatologie and Deutsche Krebshilfe, Grupo Cooperativo Brasileiro para o Tratamento do Tumor de Wilms and Sociedade Brasileira de Oncologia Pediátrica, the Spanish Society of Pediatric Haematology and Oncology and the Spanish Association Against Cancer, and SIOP-Netherlands.

15.
Hamostaseologie ; 38(3): 129-140, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29996170

RESUMO

INTRODUCTION: Regular visits at haemophilia treatment centres (HTCs) in rural regions are often dependent on the access to a private car due to lack of or limited availability of public means. Therefore, a mobile haemophilia outpatient care (MHOC) concept providing home visits to haemophilia patients has been developed by the Saarland HTC, which is located in a rural German region. METHODS: Haemophilia patients and their parents were home visited at least twice (baseline, follow-up) by trained medical staff. Socio-demographic and clinical data were collected and interviews were performed asking the patients and parents about their needs and expectations towards such a MHOC. RESULTS: Seventy-nine patients were enrolled (56 adults, 23 children), 62.0% severely affected, 48.1% on prophylaxis, with a mean age of 37.4 ± 16.4 years (17-78) and 9.8 ± 4.2 years (3-16), respectively. Median travel distance to the HTC was 43.5 km (3-200). Note that 92.4% considered an intense binding to the HTC and a MHOC concept as 'rather/very important' (88.6%). They expected from a MHOC to provide consulting and educating activities, support in elderhood issues and treatment. For 35.4%, a MHOC could currently provide additional support, mainly due to patient's immobility and need of consultancy. They mainly used services in terms of consultancy in social-legal affairs and support in contacting authorities. CONCLUSION: The results of this study support the hypothesis that a MHOC concept is a needful supplement in haemophilia comprehensive care and will improve the challenging haemophilia treatment, especially for those with limited access to HTCs or with disabilities.

16.
Nat Commun ; 9(1): 2378, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29915264

RESUMO

Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors.

17.
Bioinformatics ; 34(20): 3503-3510, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29741575

RESUMO

Motivation: Transcriptional regulators play a major role in most biological processes. Alterations in their activities are associated with a variety of diseases and in particular with tumor development and progression. Hence, it is important to assess the effects of deregulated regulators on pathological processes. Results: Here, we present REGulator-Gene Association Enrichment (REGGAE), a novel method for the identification of key transcriptional regulators that have a significant effect on the expression of a given set of genes, e.g. genes that are differentially expressed between two sample groups. REGGAE uses a Kolmogorov-Smirnov-like test statistic that implicitly combines associations between regulators and their target genes with an enrichment approach to prioritize the influence of transcriptional regulators. We evaluated our method in two different application scenarios, which demonstrate that REGGAE is well suited for uncovering the influence of transcriptional regulators and is a valuable tool for the elucidation of complex regulatory mechanisms. Availability and implementation: REGGAE is freely available at https://regulatortrail.bioinf.uni-sb.de. Supplementary information: Supplementary data are available at Bioinformatics online.

18.
Stud Health Technol Inform ; 247: 21-25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29677915

RESUMO

Predictive models can support physicians to tailor interventions and treatments to their individual patients based on their predicted response and risk of disease and help in this way to put personalized medicine into practice. In allogeneic stem cell transplantation risk assessment is to be enhanced in order to respond to emerging viral infections and transplantation reactions. However, to develop predictive models it is necessary to harmonize and integrate high amounts of heterogeneous medical data that is stored in different health information systems. Driven by the demand for predictive instruments in allogeneic stem cell transplantation we present in this paper an ontology-based platform that supports data owners and model developers to share and harmonize their data for model development respecting data privacy.


Assuntos
Ontologias Biológicas , Medicina de Precisão , Humanos , Software
19.
Pediatr Blood Cancer ; 65(8): e27085, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29693799

RESUMO

OBJECTIVE: To evaluate the value of radiotherapy boost omission in patients with intermediate-risk, stage III Wilms tumours (WT) with positive lymph nodes (LN). METHODS AND MATERIALS: All patients with intermediate-risk, stage III (LN positive) WT consecutively registered in the SIOP-WT-2001 study were included in this analysis. Endpoints were 5-year event-free survival (EFS), loco-regional control (LRC) and overall survival (OS). RESULTS: Between June 2001 and May 2015, 2,569 patients with stage I to III WT after preoperative chemotherapy were registered in the SIOP-WT-2001 study. Five hundred and twenty-three (20%) had stage III disease, of which 113 patients had stage III due to positive LN only. Of those, 101 (89%) received radiotherapy, 36 of which (36%) received, apart from flank irradiation, a boost dose to the LN positive area. Four patients (4%) did not receive any adjuvant radiotherapy. In eight patients information on radiotherapy was not available. With a median follow-up of 71 months, no difference in 5-year EFS (84% vs. 83%, P = 0.77) and LRC (96% vs. 97%, P = 0.91) was observed between patients receiving a radiotherapy boost and those without boost, respectively. Five-year OS, including salvage therapy, was excellent (boost vs. no boost: 97% vs. 95%, P = 0.58). CONCLUSIONS: Outcome data demonstrate that omission of the radiotherapy boost to the loco-regional positive lymph nodes in patients with intermediate-risk, stage III WT who receive preoperative chemotherapy and postoperative flank irradiation (14.4 Gy) can be considered a safe approach for future SIOP protocols.

20.
Klin Padiatr ; 230(4): 215-224, 2018 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-29614515

RESUMO

BACKGROUND: The German Paediatric Surveillance Unit (ESPED) was founded in 1992 to generate incidence data and detailed clinical descriptions of rare, childhood-onset diseases. METHODS: Retrospective analysis of the ESPED epidemiological data collection from 1992-2017, and analysis of all published national and international publications originating from ESPED surveys. Center of Disease Control and Prevention (CDC) criteria for evaluating surveillance systems (simplicity, flexibility, timeliness, usefulness, data quality, representativeness, stability and acceptability) were adopted and applied to available ESPED data. RESULTS: Between 1992 and 2017 ESPED completed 96 prospective studies on rare diseases in children. The 3 most frequent clinical entities were: Infectious/communicable disease (n=30), neurological diseases (n = 14) and hematologic diseases (n=10). Studies resulted in 337 publications in national and international journals. The median impact factor of the 192 journal publications with (impact factor) was 2,587 (range 0,032-28,409). The highest impact factors were seen in the fields of endocrinology/metabolism (n=130; median IF=3,534), infectious diseases (n=83; median IF=3,131) and hematology (n=37; median IF=2,497). Our analysis indicates that ESPED surveys meet CDC quality standards. CONCLUSION: ESPED surveys are an important contributor in the field of clinical epidemiology in children with rare diseases. The high quality of ESPED surveys is reflected by high-impact publications in both national and international journals.

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