title: Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol.
abstract: BACKGROUND
  Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited.
  
  
  METHODS
  Adults with disseminated medulloblastoma registered in the HIT2000 trial as observational patients and treated according to one of two different treatment regimens were analysed. The sandwich strategy MET-HIT2000AB4 consists of postoperative chemotherapy, hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy; while the HIT'91 maintenance strategy consists of postoperative craniospinal radiotherapy, and maintenance chemotherapy.
  
  
  RESULTS
  Twenty-three patients (median age: 30.7years), diagnosed from November 2001 to July 2009, and treated in 18 institutions in Germany and Austria, were eligible. The median follow-up of surviving patients was 3.99years. The 4-year event-free survival (EFS) and overall survival (OS)±standard error (SE) were 52%±12% and 91%±6%, respectively. The survival was similar in both treatment groups (HIT'91 maintenance strategy, n=9; MET-HIT2000AB4 sandwich strategy, n=14). Patients with large cell/anaplastic medulloblastoma relapsed and died (n=2; 4-year EFS/OS: 0%) and OS differed compared to patients with classic (n=11; 4-year EFS/OS: 71%/91%) and desmoplastic medulloblastoma (n=10; 4-year EFS/OS: 48%/100%), respectively (p=0.161 for EFS and p=0.033 for OS). Treatment-induced toxicities consisted mainly of neurotoxicity (50% of patients, ⩾ °II), followed by haematotoxicity and nephrotoxicity/ototoxicity. The professional outcome appeared to be negatively affected in the majority of evaluable patients (9/10).
  
  
  CONCLUSIONS
  Treatment of adults with metastatic medulloblastoma according to the intensified paediatric HIT2000 protocol was feasible with acceptable toxicities. EFS rates achieved by both chemotherapeutic protocols were favourable and appear to be inferior to those obtained in older children/adolescents with metastatic disease.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Germany. Electronic address: andre.vonbueren@med.uni-goettingen.de.
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany; Division of Pediatric Oncology, Hematology and Hemostaseology, Department of Woman's and Children's Health, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Friedrich
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Kwiecien
authors.affiliation: Department of Radiation Oncology, University Medical Center of Leipzig, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Müller
authors.affiliation: Department of Neuropathology, University of Bonn, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.affiliation: Department of Neuroradiology, University of Wuerzburg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.affiliation: Department of Neurology, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.affiliation: Department of Pediatrics, University of Wuerzburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Kuehl
authors.affiliation: Department of Radiation Oncology, University Medical Center of Leipzig, Germany.
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Kortmann
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D000367:Age Factors; D001317:Austria; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D016371:Cranial Irradiation / Q000009:adverse effects / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D060046:Maintenance Chemotherapy / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D019635:Neurosurgical Procedures / Q000009:adverse effects / Q000401:mortality; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
keywords: Adults; Brain tumour; Chemotherapy; Medulloblastoma; Prognosis; Radiotherapy; Toxicity; Treatment