showing 13 related works from this author
Comparison of RNA-seq and microarray-based models for clinical endpoint prediction
2015
Background Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model. Results We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being …
Lead-time and overdiagnosis estimation in neuroblastoma screening.
2003
In Germany, neuroblastoma is the most frequent extracranial solid childhood tumour. Its properties made it seem an ideal candidate for screening. A German trial assessed the effect of screening at one year of age from 1995-2001 in a nationwide project. We present here the methods developed for the estimation of lead-time and overdiagnosis in this project. Follow up on 1.5 million screened children and 2.1 million control children is currently available until June 2002. Ascertainment of control cohort cases and false negative cases is complete up to this date. A method for determining an empirical lead-time distribution and overdiagnosis estimate from comparing the age specific incidences in…
Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients
2018
In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in b…
Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients
2018
AbstractIn this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of non-invasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in two independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis and overall survival, revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential expression analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 …
Effective childhood cancer treatment: The impact of large scale clinical trials in Germany and Austria
2013
In Germany and Austria, more than 90% of pediatric cancer patients are enrolled into nationwide disease-specific first-line clinical trials or interim registries. Essential components are a pediatric cancer registry and centralized reference laboratories, imaging review, and tumor board assistance. The five-year overall survival rate in countries where such infrastructures are established has improved from 80% since 1995. Today, treatment intensity is tailored to the individual patient's risk to provide the highest chances of survival while minimizing deleterious late effects. Multicenter clinical trials are internationalized and serve as platforms for further improvements by novel drugs an…
Preradiation chemotherapy of children and young adults with malignant brain tumors: Results of the german pilot trial HIT'88/'89
1998
Background Preradiation chemotherapy could be beneficial in malignant brain tumors, because the blood-brain tumor-barrier is disrupted after surgery, bone marrow recovery--essential for intense chemotherapy--is still intact, and CNS toxicity and ototoxicity of active drugs are lower before irradiation of a child's brain. Patients and methods A neoadjuvant phase 2 and a single arm pilot trial were initiated to investigate the efficacy and toxicity of an intense multidrug regimen before radiotherapy in 147 patients aged between 3 and 29; 9 years with medulloblastoma (94), malignant glioma (22), ependymoma (21), and stPNET (10). They were treated with one or two cycles consisting of procarbazi…
Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the Intern…
2011
Abstract Purpose Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970’s, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database. Patients and methods Data from 11,037 children with NB (1974–2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adj…
Incidence, Trends, and Survival of Children With Embryonal Tumors.
2015
BACKGROUND: Central nervous system (CNS) and non-CNS embryonal tumors occur principally in children and are rarely seen in adults. The incidence rates for rare entities such as atypical teratoid/rhabdoid tumors (AT/RT) or primitive neuroectodermal tumors in the CNS are rarely published. Incidence rates for certain subgroups, such as hepatoblastomas, have been increasing in some countries. METHODS: Data of 8337 embryonal tumors, registered in children (0–14 years) between 1991 and 2012 (for AT/RT 2000–2012) in the population-based German Childhood Cancer Registry with complete national coverage were analyzed for incidence rates, time trends, and survival. RESULTS: For most entities, the inc…
Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular progn…
2014
Abstract Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression–based classification and established prognostic markers. Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n = 634) by Kaplan–Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity, 0.93; specificity, 0.97) in the validation coh…
Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q
2006
In localized neuroblastoma, the identification of patients requiring intensive treatment is still difficult. We retrospectively analyzed data of 280 single copy MYCN stage 2 and 3 neuroblastoma patients with gross residual tumor after initial surgery. The 3-year-event free survival of the total group was 83+/-2%, and 3-year-overall survival was 92+/-2%. Patients < or=1.5 years had a better outcome than older children. Deletions/imbalances of chromosome 1p were found in 9/90 patients and were associated with a higher event rate but not with a higher death rate. Aberrations of chromosome 11q in 14/91 patients were correlated with a higher event and death rate. Multivariate analysis identified…
Case Control Study of Neuroblastoma in West-Germany after the Chernobyl Accident
1996
Background To explore possible causes of a 1988 incidence peak of infant neuroblastoma in west German regions which were contaminated with more than 6000 Bq/m2 Cs137 from the Chernobyl accident. The primary working hypothesis was that parents of the diseased children had been contaminated by an excessive intake of locally produced food, especially mushrooms or deer. Design Case control study with 1:2 (cases:controls) matching. Data were collected from the children's parents by questionnaires and telephone interviews. Setting Nation-wide study (former FRG) based on the German Childhood Cancer Registry. Subjects Cases born in 1988 and reported with a neuroblastoma to the registry until March …
Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy
2008
To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for an…
Children may not benefit from neuroblastoma screening at 1 year of age. Updated results of the population based controlled trial in Germany
2003
Neuroblastoma is the second most frequent malignancy in childhood. We investigated whether screening for neuroblastoma at 1 year of age reduces the incidence of metastatic disease or mortality. Screening was offered in 6 of the 16 German states from 1995 to 2000 with the remaining states serving as controls. We studied 2,581,188 children in the screening area born between 1994 and 1999 and 2,117,600 in the control area. We compared mortality from neuroblastoma and the incidence of disseminated disease in the two groups. The screened group and the control group had similar rates of stage 4 neuroblastoma and mortality due to neuroblastoma. Comparison of the screened group and the control area…