Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

Autor: Kolodziejczak AS; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany., Guerrini-Rousseau L; Department of Children and Adolescents Oncology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.; Molecular Predictors and New Targets in Oncology, Inserm U981 Team 'Genomics and Oncogenesis of pediatric Brain Tumors,' Gustave Roussy, Université Paris-Saclay, Villejuif, France., Planchon JM; Department of Diagnostic and Theranostic Medicine, Somatic Genetics Unit, Institut Curie, Paris-Science Lettres University, Paris, France., Ecker J; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany., Selt F; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany., Mynarek M; Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Obrecht D; Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Sill M; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Autry RJ; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Stutheit-Zhao E; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Hirsch S; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Amouyal E; SIREDO Pediatric Oncology Center, Institut Curie, Paris-Science Lettres University, Paris, France., Dufour C; Department of Children and Adolescents Oncology, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France.; Molecular Predictors and New Targets in Oncology, Inserm U981 Team 'Genomics and Oncogenesis of pediatric Brain Tumors,' Gustave Roussy, Université Paris-Saclay, Villejuif, France., Ayrault O; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France., Torrejon J; Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France Université Paris Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France., Waszak SM; Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.; Department of Neurology, University of California, San Francisco, CA, USA., Ramaswamy V; Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.; Division of Hematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada., Pentikainen V; Division of Hematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Hospital, Helsinki, Finland., Demir HA; Department of Pediatric Hematology-Oncology, Private Memorial Ankara Hospital, Ankara, Turkey., Clifford SC; Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Newcastle upon Tyne, United Kingdom., Schwalbe EC; Wolfson Childhood Cancer Research Centre, Newcastle University Centre for Cancer, Newcastle upon Tyne, United Kingdom.; Applied Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom., Massimi L; Pediatric Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University Medical School, Rome, Italy., Snuderl M; Department of Pathology, New York University Langone Health, New York City, NY, USA., Galbraith K; Department of Pathology, New York University Langone Health, New York City, NY, USA., Karajannis MA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Hill K; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Li BK; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Walsh M; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., White CL; Victorian Clinical Genetics Services, Parkville, Australia.; Hudson Institute of Medical Research, Clayton, Australia.; Department of Molecular and Translational Science, Monash University, Clayton, Australia., Redmond S; Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland., Loizos L; Pediatric Oncology/Hematology/Immunology at the Medical School of the University of Nicosia, Nicosia, Cyprus., Jakob M; Department of Paediatric Haematology, Oncology and Stem-Cell Transplantation, University Hospital Regensburg, Regensburg, Germany., Kordes UR; Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schmid I; Paediatric Haematology and Oncology, Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany., Hauer J; Pediatric Haematology and Oncology, University Hospital Carl Gustav Carus, Dresden, Germany., Blattmann C; Paediatric Haematology, Oncology and Immunology, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany., Filippidou M; Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, Athens, Greece., Piccolo G; Neuro-Oncology Unit, IRCCS Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy., Scheurlen W; Paediatric Haematology and Oncology, Cnopfsche Paediatric Clinic, Nurnberg, Germany., Farrag A; Department of Paediatric Haematology, Oncology and Stem-Cell Transplantation, Paediatric Clinic, University Hospital Aachen, Aachen, Germany.; Department of Pediatric Oncology, South Egypt Cancer Institute, Assiut University, Egypt., Grund K; Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany., Sutter C; Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany., Pietsch T; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Frank S; Division of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland., Schewe DM; Department of Pediatrics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany., Malkin D; Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Ben-Arush M; Pediatric Hematology Oncology, Rambam Medical Center, Haifa, Israel., Sehested A; Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Copenhagen University Hospital, Copenhagen, Denmark., Wong TT; Division of Pediatric Neurosurgery, Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan., Wu KS; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Liu YL; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Carceller F; Paediatric and Adolescent Oncology Drug Development Team, Children and Young People's Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom., Mueller S; Department of Neurology, Neurosurgery and Pediatrics, University of California, San Francisco, USA., Stoller S; Department of Neurology, University of California, San Francisco, USA., Taylor MD; Division of Neurosurgery, Program in Developmental and Stem Cell Biology, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada., Tabori U; Division of Hematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada., Bouffet E; Division of Hematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Division of Haematology/ Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada., Kool M; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Sahm F; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, and CCU Neuropathology, German Cancer Institute (DKF), Heidelberg, Germany., von Deimling A; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, and CCU Neuropathology, German Cancer Institute (DKF), Heidelberg, Germany., Korshunov A; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, and CCU Neuropathology, German Cancer Institute (DKF), Heidelberg, Germany., von Hoff K; Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark., Kratz CP; Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany., Sturm D; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.; Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Jones DTW; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Rutkowski S; Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., van Tilburg CM; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany., Witt O; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany., Bougeard G; Univ Rouen Normandie, Inserm U1245 and CHU Rouen, Department of Genetics, F-76000 Rouen, France., Pajtler KW; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Pfister SM; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.; Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Bourdeaut F; SIREDO Pediatric Oncology Center, Institut Curie, Paris-Science Lettres University, Paris, France., Milde T; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; CCU Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; National Center for Tumor Diseases (NCT), Heidelberg, Germany.; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Neuro-oncology [Neuro Oncol] 2023 Dec 08; Vol. 25 (12), pp. 2273-2286.
DOI: 10.1093/neuonc/noad114
Abstrakt: Background: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients.
Methods: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated.
Results: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively).
Conclusions: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze: MEDLINE