title: Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology.
abstract: This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy. Otherwise, secondary surgery, radiotherapy, and consolidation chemotherapy were recommended. At a median follow-up of 4.5 years, the 5-year event-free survival (EFS) and overall survival (OS) rates (± standard error) for 45 patients (median age, 2.5 years) were 57% ± 8% and 80% ± 6%, respectively. Nineteen patients with desmoplastic/nodular MB variants had better 5-year EFS and OS rates (90% ± 7% and 100% ± 0%, respectively) than did 23 patients with classic MB (30% ± 11% and 68% ± 10%, respectively; P < .001 for EFS; P = .008 for OS). Five-year EFS and OS rates for 3 children with anaplastic MB were 33% ± 27%. Desmoplastic/nodular histology was an independent prognostic factor for EFS. Twenty-nine of 30 patients without postoperative residual tumor remained in continuous complete remission. Our results confirm that histology of MB variants is a strong prognostic factor in this age group. Sustained tumor control can be achieved by this chemotherapy regimen in young children with desmoplastic/nodular MB variants. For children with non-desmoplastic/nonnodular MB variants, for which predominantly local relapses lead to less favorable survival rates, local radiotherapy has been introduced after chemotherapy since 2006.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany, Martinistr. 52, D-20246 Hamburg, Germany. a.von-bueren@uke.de
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Nicolas U
authors.initials: NU
authors.lastname: Gerber
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Frank
authors.initials: F
authors.lastname: Deinlein
authors.forename: Isabella
authors.initials: I
authors.lastname: Zwiener
authors.forename: Andreas
authors.initials: A
authors.lastname: Faldum
authors.forename: Gudrun
authors.initials: G
authors.lastname: Fleischhack
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Juergen
authors.initials: J
authors.lastname: Krauss
authors.forename: Joachim
authors.initials: J
authors.lastname: Kuehl
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Kortmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000473:pathology* / Q000628:therapy*; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D002955:Leucovorin / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008527:Medulloblastoma / Q000473:pathology* / Q000628:therapy*; D008727:Methotrexate / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011446:Prospective Studies; D011878:Radiotherapy; D012074:Remission Induction; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D002955:Leucovorin; D008727:Methotrexate