title: Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy.
abstract: BACKGROUND
  Especially in young children, primitive neuroectodermal tumors of the central nervous system (CNS-PNET) and pineoblastomas are associated with an unfavorable outcome, and only a few prospective trials have been conducted thus far.
  
  
  METHODS
  From January 2001 through January 2005, 17 eligible children aged <4 years with CNS-PNET not otherwise specified (n = 8), ependymoblastoma (n = 1), or pineoblastoma (n = 8) confirmed by central review were prospectively treated in the trial HIT 2000. In nonmetastatic disease (n = 11), up to 5 postoperative cycles of HIT-SKK systemic multiagent chemotherapy (8 months duration), followed by craniospinal radiotherapy (CSI), were given. In metastatic disease (M1-M3, n = 6), treatment consisted of a shorter induction chemotherapy (2-3 months) with carboplatin and etoposide, followed by tandem high-dose chemotherapy (HDCT) in case of good response to induction. During induction and HDCT, patients received intraventricular methotrexate. CSI was applied to all patients with poor response to induction or residual disease after HDCT and was optional for patients with residual disease before HDCT.
  
  
  RESULTS
  Five-year event-free survival and overall survival rates ± standard error for all eligible patients were 24% ± 10% and 40% ± 12%, respectively (median follow-up of survivors: 8.3 years). Only one patient with nonmetastatic disease remained free of relapse/progressive disease during induction. Three of 6 patients with metastatic disease responded to induction and received tandem-HDCT, followed by preventive CSI, and remain in continuous complete remission.
  
  
  CONCLUSIONS
  Short intensive induction chemotherapy followed by tandem-HDCT in young children with CNS-PNET/pineoblastomas seems to be superior to the prolonged and less intensive induction regimen.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Friedrich
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.forename: Nicolas U
authors.initials: NU
authors.lastname: Gerber
authors.forename: Holger
authors.initials: H
authors.lastname: Ottensmeier
authors.forename: Frank
authors.initials: F
authors.lastname: Deinlein
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Robert
authors.initials: R
authors.lastname: Kwiecien
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Andreas
authors.initials: A
authors.lastname: Faldum
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*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002675:Child, Preschool; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D060787:Neoplasm Grading; D018365:Neoplasm, Residual / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018242:Neuroectodermal Tumors, Primitive / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009483:Neuropsychological Tests; D010870:Pineal Gland / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D010871:Pinealoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D008727:Methotrexate