Back
Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort
Journal article

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

  • Mynarek, Martin Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • von Hoff, Katja Department of Pediatric Oncology, Hematology and Stem Cell Transplantation, Charite – University Medical Center Berlin, Berlin, Germany
  • Pietsch, Torsten Institute of Neuropathology, Brain Tumor Reference Center of the German Society for Neuropathology and Neuroanatomy, University of Bonn, German Center for Neurodegenerative Diseases, Bonn, Germany
  • Ottensmeier, Holger Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Wuerzburg, Germany
  • Warmuth-Metz, Monika Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany
  • Bison, Brigitte Institute of Diagnostic and Interventional Neuroradiology, University Hospital Wuerzburg, Wuerzburg, Germany
  • Pfister, Stefan Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany
  • Korshunov, Andrey Clinical Cooperation Unit Neuropathology, German Cancer Research Center; and Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
  • Sharma, Tanvi Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
  • Jaeger, Natalie Division of Pediatric Neurooncology (B062), German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany
  • Ryzhova, Marina Department of Neuropathology, N. N. Burdenko Neurosurgical Institute, Moscow, Russia
  • Zheludkova, Olga Department of Pediatric Oncology, Russian Scientific Center of Roentgenoradiology, Moscow, Russia
  • Golanov, Andrey Department of Stereotactic Radiotherapy and Radiosurgery, N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russia
  • Rushing, Elisabeth Jane Institute of Neuropathology, University Medical Center Zurich, Zurich, Switzerland
  • Hasselblatt, Martin Institute of Neuropathology, University Hospital Muenster, Muenster, Germany
  • Koch, Arend Department of Neuropathology, Charite – University Medical Center Berlin, Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany
  • Schüller, Ulrich Department of Neuropathology, University Medical Center Hamburg-Eppendorf; and Research Institute Children's Cancer Center Hamburg, Hamburg, Germany
  • von Deimling, Andreas Clinical Cooperation Unit Neuropathology, German Cancer Research Center; and Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
  • Sahm, Felix Clinical Cooperation Unit Neuropathology, German Cancer Research Center; and Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany
  • Sill, Martin Division of Pediatric Neurooncology (B062), German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany
  • Riemenschneider, Markus J. Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany
  • Dohmen, Hildegard Institute for Neuropathology, University Hospital Gießen and Marburg, Gießen, Germany
  • Monoranu, Camelia Maria Institute of Pathology, Department of Neuropathology, University of Wuerzburg; and Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany
  • Sommer, Clemens Institute for Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
  • Staszewski, Ori Institute of Neuropathology and Berta-Ottenstein-Programme for Advanced Clinician Scientists, University of Freiburg, Freiburg, Germany
  • Mawrin, Christian Institute for Neuropathology, University of Magdeburg, Magdeburg, Germany
  • Schittenhelm, Jens Department of Neuropathology, Institute for Pathology and Neuropathology, University Medical Center Tuebingen, Tuebingen, Germany
  • Brück, Wolfgang Institute for Neuropathology, University Medical Center Goettingen, Goettingen, Germany
  • Filipski, Katharina Institute of Neurology (Edinger Institute), University Hospital, Frankfurt Am Main; German Cancer Consortium, Partner Site Frankfurt/Mainz; and German Cancer Research Center, Heidelberg, Germany
  • Hartmann, Christian Department of Neuropathology, Institute for Pathology, Hannover Medical School, Hannover, Germany
  • Meinhardt, Matthias Institute for Pathology, University Medical Center Carl Gustav Carus, Technical University Dresden, Dresden, Germany
  • Pietschmann, Klaus Department for Radiotherapy, Poliklinik Chemnitz, Chemnitz, Germany
  • Haberler, Christine Institute of Neurology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  • Slavc, Irene Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
  • Gerber, Nicolas U. Department of Oncology and Children's Research Centre, University Children's Hospital, Zurich, Switzerland
  • Grotzer, Michael Department of Oncology and Children's Research Centre, University Children's Hospital, Zurich, Switzerland
  • Benesch, Martin Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
  • Schlegel, Paul Gerhardt Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Wuerzburg, Germany
  • Deinlein, Frank Department of Pediatric Hematology and Oncology, University Children's Hospital Wuerzburg, Wuerzburg, Germany
  • von Bueren, André O. Department of Pediatrics, Obstetrics and Gynecology, Division of Pediatric Hematology and Oncology, University Hospital of Geneva; and Department of Pediatrics, CANSEARCH Research Laboratory, University of Geneva, Geneva, Switzerland
  • Friedrich, Carsten Division of Pediatric Oncology and Hematology, University Children's Hospital Rostock, Rostock, Germany
  • Juhnke, Björn-Ole Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Obrecht, Denise Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Fleischhack, Gudrun Pediatric Hematology and Oncology, Pediatrics III, University Hospital of Essen, Essen, Germany
  • Kwiecien, Robert Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany
  • Faldum, Andreas Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany
  • Kortmann, Rolf Dieter Department of Radiation Oncology, University of Leipzig, Leipzig, Germany
  • Kool, Marcel Division of Pediatric Neurooncology (B062), German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany
  • Rutkowski, Stefan Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Show more…
Published in:
  • Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2020, vol. 38, no. 18, p. 2028-2040
Cancer Research
Oncology
English PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided into iSHH-I and iSHH-II subtypes in the HIT-2000-BIS4 cohort and a validation cohort (n = 71) from the HIT group and Russia. RESULTS Five years after diagnosis, patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN; n = 42) had 93% progression-free survival (5y-PFS), 100% overall survival (5y-OS), and 93% CSI-free (5y-CSI-free) survival. Patients with CMB/LCA (n = 45) had 37% 5y-PFS, 62% 5y-OS, and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in patients with CMB/LCA. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH-INF subgroup. Group 3 patients (5y-PFS, 36%; n = 14) relapsed more frequently than the SHH-INF group (5y-PFS, 93%; n = 28) or group 4 patients (5y-PFS, 83%; n = 6; P < .001). SHH-INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I, 73%, v iSHH-II, 83%; P = .25; n = 99). Intelligence quotient (IQ) was significantly lower in patients after CSI (mean IQ, 90 [no radiotherapy], v 74 [CSI]; P = .012). CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in patients with non-wingless (WNT)/non-SHH disease with CMB/LCA was not improved by local radiotherapy. Patients with group 4 disease had more favorable survival rates than those with group 3 medulloblastoma.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/235664
Statistics
Document views: 25 File downloads: