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Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma
R. Kumar, KS. Smith, M. Deng, C. Terhune, GW. Robinson, BA. Orr, APY. Liu, T. Lin, CA. Billups, M. Chintagumpala, DC. Bowers, TE. Hassall, JR. Hansford, DA. Khuong-Quang, JR. Crawford, AE. Bendel, S. Gururangan, K. Schroeder, E. Bouffet, U....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu srovnávací studie, časopisecké články, multicentrická studie, práce podpořená grantem
Grantová podpora
CIHR - Canada
NLK
Free Medical Journals
od 2004 do Před 1 rokem
Open Access Digital Library
od 1999-01-01
PubMed
33502920
DOI
10.1200/jco.20.01359
Knihovny.cz E-zdroje
- MeSH
- časové faktory MeSH
- dítě MeSH
- epigenom MeSH
- epigenomika MeSH
- klinické zkoušky jako téma MeSH
- kojenec MeSH
- lidé MeSH
- lokální recidiva nádoru * MeSH
- meduloblastom genetika mortalita sekundární terapie MeSH
- metylace DNA * MeSH
- nádorové biomarkery genetika MeSH
- nádory mozečku genetika mortalita patologie terapie MeSH
- opakovaná terapie MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- výsledek terapie MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
PURPOSE: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. RESULTS: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. CONCLUSION: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.
Children's National Hospital Washington DC
Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany
Department of Biostatistics St Jude Children's Research Hospital Memphis TN
Department of Developmental Neurobiology St Jude Children's Research Hospital Memphis TN
Department of Haematology and Oncology Royal Children's Hospital Parkville Victoria Australia
Department of Hematology and Oncology University Hospital Hamburg Eppendorf Hamburg Germany
Department of Hematology Oncology Children's Hospital of Minnesota Minneapolis MN
Department of Hematology Oncology Nemours Alfred 1 duPont Hospital for Children Wilmington DE
Department of Hematology Oncology Seattle Children's Hospital Seattle WA
Department of Neuro Oncology Russian Scientific Center of Radiology Moscow Russia
Department of Neurology Hospital de Santa Maria Lisbon Portugal
Department of Neuropathology NN Burdenko Neurosurgical Institute Moscow Russia
Department of Neuroradiology NN Burdenko Neurosurgical Institute Moscow Russia
Department of Oncology St Jude Children's Research Hospital Memphis TN
Department of Pathology Dalhousie University Halifax Nova Scotia Canada
Department of Pathology Duke University Medical Center Durham NC
Department of Pathology St Jude Children's Research Hospital Memphis TN
Department of Pediatric Oncology Children's Hospital at Westmead Westmead New South Wales Australia
Department of Pediatrics Division of Oncology Cincinnati Children's Hospital Cincinnati OH
Department of Pediatrics Pediatric Neurology Oregon Health and Science University Portland OR
Department of Pediatrics University Hospital Essen Essen Germany
Department of Radiation Oncology St Jude Children's Research Hospital Memphis TN
Department of Radiation Oncology University of Texas MD Anderson Cancer Center Houston TX
Departments of Neurology and Pediatrics Stanford University Palo Alto CA
Division of Haematology Oncology Hospital for Sick Children Toronto Ontario Canada
Division of Neurology Centre Hospitalier Universitaire Sainte Justine Montreal Québec Canada
Division of Pediatric Hematology Oncology Children's Hospital of Los Angeles Los Angeles CA
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
Graduate School of Biomedical Sciences St Jude Children's Research Hospital Memphis TN
Hopp Children's Cancer Center Heidelberg Germany
Pediatric Glioma Research Group German Cancer Research Center Heidelberg Germany
Preston Robert Tisch Brain Tumor Center Duke University Durham NC
Princess Maxima Center for Pediatric Oncology Utrecht the Netherlands
Research Center for Genetic Medicine Children's National Health System Washington DC
Texas Children's Cancer Center Baylor College of Medicine Houston TX
Citace poskytuje Crossref.org
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