-
Something wrong with this record ?
Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study
K. von Hoff, C. Haberler, F. Schmitt-Hoffner, E. Schepke, T. de Rojas, S. Jacobs, M. Zapotocky, D. Sumerauer, M. Perek-Polnik, C. Dufour, D. van Vuurden, I. Slavc, J. Gojo, JC. Pickles, NU. Gerber, M. Massimino, MJ. Gil-da-Costa, M. Garami, E....
Language English Country Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1999 to 1 year ago
PubMed Central
from 1999 to 1 year ago
Europe PubMed Central
from 1999 to 1 year ago
Open Access Digital Library
from 1999-01-01
Medline Complete (EBSCOhost)
from 2004-01-01 to 1 year ago
- MeSH
- Forkhead Transcription Factors MeSH
- Neoplasms, Germ Cell and Embryonal * diagnosis genetics therapy MeSH
- Humans MeSH
- Pathology, Molecular MeSH
- Central Nervous System Neoplasms * diagnosis genetics therapy MeSH
- Brain Neoplasms * diagnosis genetics therapy MeSH
- Neuroectodermal Tumors, Primitive * diagnosis genetics therapy MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307). Additional cases (n = 66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n = 292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58 (19%) cases as ETMR, 57 (19%) as high-grade glioma (HGG), 36 (12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63% ± 7%, OS: 85% ± 5%, n = 63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18% ± 6% and 22% ± 7%, and 5-year OS of 24% ± 6% and 25% ± 7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk CSI-based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments.
2nd Department of Pediatrics Semmelweis University Budapest Hungary
2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic
Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany
Department of Neurooncology Russian Scientific Center of Radiology Moscow Russia
Department of Neuropathology Burdenko Neurosurgical Institute Moscow Russia
Department of Neuropathology Heidelberg University Hospital Heidelberg Germany
Department of Neuroradiology Burdenko Neurosurgical Institute Moscow Russia
Department of Oncology The Children's Memorial Health Institute University of Warsaw Warsaw Poland
Department of Oncology University Children's Hospital Zurich Switzerland
Department of Pathology Amsterdam University Medical Center VUmc Amsterdam the Netherlands
Department of Pathology Johns Hopkins University Baltimore Maryland USA
Department of Pathology NYU Langone Health and School of Medicine New York New York USA
Department of Pathology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Pathology University Medical Centre Utrecht Utrecht the Netherlands
Department of Pathomorphology Children's Memorial Health Institute Warsaw Poland
Department of Pediatric and Adolescent Oncology Gustave Roussy Cancer Center Villejuif France
Department of Pediatrics and Adolescent Medicine Rigshospitalet Copenhagen Denmark
Department of Pediatrics KU Leuven and University Hospitals Leuven Leuven Belgium
Division of Pathology The Hospital for Sick Children Toronto Canada
Division of Pediatric and Adolescent Medicine Oslo University Hospital Oslo Norway
Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany
Faculty of Biosciences Heidelberg University Heidelberg Germany
German Cancer Consortium Heidelberg Germany
Hopp Children's Cancer Center Heidelberg Germany
INSERM Molecular Predictors and New Targets in Oncology Paris Saclay University Villejuif France
Institute of Biostatistics and Clinical Research University of Muenster Muenster Germany
Institute of Neuropathology University Medical Center Hamburg Eppendorf Hamburg Germany
Institute of Neuropathology University Medical Center Zurich Zurich Switzerland
Institute of Translational Research University of Liverpool Liverpool UK
Paediatric Haematology and Oncology Division Hospital Universitari Vall d'Hebron Barcelona Spain
Pediatric Glioma Research German Cancer Research Center Heidelberg Germany
Pediatric OncoGenomics Unit Children's University Hospital Niño Jesús Madrid Spain
Pediatric Oncology Department Hospital Sant Joan de Déu Barcelona Spain
Pediatric Oncology Department University Hospital São João Porto Portugal
Pediatric Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy
Princess Máxima Center for Pediatric Oncology Utrecht the Netherlands
Research Institute Children's Cancer Center Hamburg Hamburg Germany
Service of Hematology Oncology Hospital JP Garrahan Buenos Aires Argentina
The Queen Silvia Children's Hospital Sahlgrenska University Hospital Gothenburg Sweden
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc22003845
- 003
- CZ-PrNML
- 005
- 20220127145811.0
- 007
- ta
- 008
- 220113s2021 xxk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1093/neuonc/noab136 $2 doi
- 035 __
- $a (PubMed)34077956
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxk
- 100 1_
- $a von Hoff, Katja $u Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- 245 10
- $a Therapeutic implications of improved molecular diagnostics for rare CNS embryonal tumor entities: results of an international, retrospective study / $c K. von Hoff, C. Haberler, F. Schmitt-Hoffner, E. Schepke, T. de Rojas, S. Jacobs, M. Zapotocky, D. Sumerauer, M. Perek-Polnik, C. Dufour, D. van Vuurden, I. Slavc, J. Gojo, JC. Pickles, NU. Gerber, M. Massimino, MJ. Gil-da-Costa, M. Garami, E. Kumirova, A. Sehested, D. Scheie, O. Cruz, L. Moreno, J. Cho, B. Zeller, N. Bovenschen, M. Grotzer, D. Alderete, M. Snuderl, O. Zheludkova, A. Golanov, K. Okonechnikov, M. Mynarek, BO. Juhnke, S. Rutkowski, U. Schüller, B. Pizer, B. von Zezschwitz, R. Kwiecien, M. Wechsung, F. Konietschke, EI. Hwang, D. Sturm, SM. Pfister, A. von Deimling, EJ. Rushing, M. Ryzhova, P. Hauser, M. Łastowska, P. Wesseling, F. Giangaspero, C. Hawkins, D. Figarella-Branger, C. Eberhart, P. Burger, M. Gessi, A. Korshunov, TS. Jacques, D. Capper, T. Pietsch, M. Kool
- 520 9_
- $a BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumors with multilayered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n = 307). Additional cases (n = 66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n = 292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58 (19%) cases as ETMR, 57 (19%) as high-grade glioma (HGG), 36 (12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63% ± 7%, OS: 85% ± 5%, n = 63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18% ± 6% and 22% ± 7%, and 5-year OS of 24% ± 6% and 25% ± 7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk CSI-based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments.
- 650 12
- $a nádory mozku $x diagnóza $x genetika $x terapie $7 D001932
- 650 12
- $a nádory centrálního nervového systému $x diagnóza $x genetika $x terapie $7 D016543
- 650 _2
- $a forkhead transkripční faktory $7 D051858
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a germinální a embryonální nádory $x diagnóza $x genetika $x terapie $7 D009373
- 650 12
- $a primitivní neuroektodermové nádory $x diagnóza $x genetika $x terapie $7 D018242
- 650 _2
- $a molekulární patologie $7 D057089
- 650 _2
- $a retrospektivní studie $7 D012189
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Haberler, Christine $u Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Schmitt-Hoffner, Felix $u Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany $u Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
- 700 1_
- $a Schepke, Elizabeth $u The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
- 700 1_
- $a de Rojas, Teresa $u Pediatric OncoGenomics Unit, Children's University Hospital Niño Jesús, Madrid, Spain
- 700 1_
- $a Jacobs, Sandra $u Department of Pediatrics, KU Leuven and University Hospitals Leuven, Leuven, Belgium
- 700 1_
- $a Zapotocky, Michal $u Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
- 700 1_
- $a Sumerauer, David $u Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
- 700 1_
- $a Perek-Polnik, Marta $u Department of Oncology, The Children's Memorial Health Institute, University of Warsaw, Warsaw, Poland
- 700 1_
- $a Dufour, Christelle $u Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Center, Villejuif, France $u INSERM, Molecular Predictors and New Targets in Oncology, Paris-Saclay University, Villejuif, France
- 700 1_
- $a van Vuurden, Dannis $u Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- 700 1_
- $a Slavc, Irene $u Department of Pediatrics and Adolescent Medicine and Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Gojo, Johannes $u Department of Pediatrics and Adolescent Medicine and Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
- 700 1_
- $a Pickles, Jessica C $u Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK $u Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- 700 1_
- $a Gerber, Nicolas U $u Department of Oncology, University Children's Hospital, Zurich, Switzerland
- 700 1_
- $a Massimino, Maura $u Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- 700 1_
- $a Gil-da-Costa, Maria Joao $u Pediatric Oncology Department, University Hospital São João, Porto, Portugal
- 700 1_
- $a Garami, Miklos $u 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Kumirova, Ella $u Department of Neuro-Oncology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- 700 1_
- $a Sehested, Astrid $u Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen,Denmark
- 700 1_
- $a Scheie, David $u Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- 700 1_
- $a Cruz, Ofelia $u Pediatric Oncology Department, Hospital Sant Joan de Déu, Barcelona, Spain
- 700 1_
- $a Moreno, Lucas $u Paediatric Haematology and Oncology Division, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- 700 1_
- $a Cho, Jaeho $u Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
- 700 1_
- $a Zeller, Bernward $u Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
- 700 1_
- $a Bovenschen, Niels $u Department of Pathology, University Medical Centre Utrecht, Utrecht, the Netherlands
- 700 1_
- $a Grotzer, Michael $u Department of Oncology, University Children's Hospital, Zurich, Switzerland
- 700 1_
- $a Alderete, Daniel $u Service of Hematology/Oncology, Hospital JP Garrahan, Buenos Aires, Argentina
- 700 1_
- $a Snuderl, Matija $u Department of Pathology, NYU Langone Health and School of Medicine, New York, New York, USA
- 700 1_
- $a Zheludkova, Olga $u Department of Neurooncology, Russian Scientific Center of Radiology, Moscow, Russia
- 700 1_
- $a Golanov, Andrey $u Department of Neuroradiology, Burdenko Neurosurgical Institute, Moscow, Russia
- 700 1_
- $a Okonechnikov, Konstantin $u Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
- 700 1_
- $a Mynarek, Martin $u Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 700 1_
- $a Juhnke, Björn Ole $u Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 700 1_
- $a Rutkowski, Stefan $u Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 700 1_
- $a Schüller, Ulrich $u Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany $u Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany $u Research Institute Children's Cancer Center Hamburg, Hamburg, Germany
- 700 1_
- $a Pizer, Barry $u Institute of Translational Research, University of Liverpool, Liverpool, UK
- 700 1_
- $a von Zezschwitz, Barbara $u Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- 700 1_
- $a Kwiecien, Robert $u Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany
- 700 1_
- $a Wechsung, Maximilian $u Institute of Biometry and Clinical Epidemiology, Charité University Medicine and Berlin Institute of Health, Berlin, Germany
- 700 1_
- $a Konietschke, Frank $u Institute of Biometry and Clinical Epidemiology, Charité University Medicine and Berlin Institute of Health, Berlin, Germany
- 700 1_
- $a Hwang, Eugene I $u Department of Pediatric Hematology-Oncology, Center for Cancer and Immunology Research and Neuroscience Research, Children's National Medical Center, Washington DC, USA
- 700 1_
- $a Sturm, Dominik $u Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany $u Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany
- 700 1_
- $a Pfister, Stefan M $u Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany $u Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany
- 700 1_
- $a von Deimling, Andreas $u Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany $u Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 700 1_
- $a Rushing, Elisabeth J $u Institute of Neuropathology, University Medical Center Zurich, Zurich, Switzerland
- 700 1_
- $a Ryzhova, Marina $u Department of Neuropathology, Burdenko Neurosurgical Institute, Moscow, Russia
- 700 1_
- $a Hauser, Peter $u 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary
- 700 1_
- $a Łastowska, Maria $u Department of Pathomorphology, Children's Memorial Health Institute, Warsaw, Poland
- 700 1_
- $a Wesseling, Pieter $u Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands $u Department of Pathology, Amsterdam University Medical Center/VUmc, Amsterdam, the Netherlands
- 700 1_
- $a Giangaspero, Felice $u Department of Radiological, Oncological and Anatomopathological Sciences, Sapienza University of Rome, Rome, Italy $u IRCCS Neuromed, Pozzilli (IS), Italy
- 700 1_
- $a Hawkins, Cynthia $u Division of Pathology, The Hospital for Sick Children, Toronto, Canada
- 700 1_
- $a Figarella-Branger, Dominique $u Inst Neurophysiopathol, CHU Timone, Service d'Anatomie Pathologique et de Neuropathologie, Aix-Marseille Univ, APHM, CNRS, INP, Marseille, France
- 700 1_
- $a Eberhart, Charles $u Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
- 700 1_
- $a Burger, Peter $u Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
- 700 1_
- $a Gessi, Marco $u Neuropathology Unit, Division of Pathology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
- 700 1_
- $a Korshunov, Andrey $u Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany $u Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 700 1_
- $a Jacques, Tom S $u Department of Histopathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
- 700 1_
- $a Capper, David $u Department of Neuropathology, Charité University Medicine and Berlin Institute of Health, Berlin, Germany $u German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 700 1_
- $a Pietsch, Torsten $u Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, DZNE German Center for Neurodegenerative Diseases, Bonn, Germany
- 700 1_
- $a Kool, Marcel $u Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany $u Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany $u Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- 773 0_
- $w MED00193498 $t Neuro-oncology $x 1523-5866 $g Roč. 23, č. 9 (2021), s. 1597-1611
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/34077956 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y p $z 0
- 990 __
- $a 20220113 $b ABA008
- 991 __
- $a 20220127145807 $b ABA008
- 999 __
- $a ok $b bmc $g 1751342 $s 1154994
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2021 $b 23 $c 9 $d 1597-1611 $e 20210901 $i 1523-5866 $m Neuro-oncology $n Neuro Oncol $x MED00193498
- LZP __
- $a Pubmed-20220113
