title: Hyperfractionated accelerated radiotherapy in the Milan strategy for metastatic medulloblastoma.
abstract: OBJECTIVE
  With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after intensive sequential chemotherapy.
  
  
  METHODS
  Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue.
  
  
  RESULTS
  Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far.
  
  
  CONCLUSIONS
  HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
authors.affiliation: Radiotherapy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Gandola
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.forename: Graziella
authors.initials: G
authors.lastname: Cefalo
authors.forename: Carlo
authors.initials: C
authors.lastname: Solero
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.forename: Emilia
authors.initials: E
authors.lastname: Pecori
authors.forename: Daria
authors.initials: D
authors.lastname: Riva
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.forename: Emanuele
authors.initials: E
authors.lastname: Pignoli
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Roberto
authors.initials: R
authors.lastname: Luksch
authors.forename: Serena
authors.initials: S
authors.lastname: Berretta
authors.forename: Geraldina
authors.initials: G
authors.lastname: Poggi
authors.forename: Veronica
authors.initials: V
authors.lastname: Biassoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrari
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
authors.forename: Claudio
authors.initials: C
authors.lastname: Favre
authors.forename: Iacopo
authors.initials: I
authors.lastname: Sardi
authors.forename: Monica
authors.initials: M
authors.lastname: Terenziani
authors.forename: Franca
authors.initials: F
authors.lastname: Fossati-Bellani
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008727:Methotrexate / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D008727:Methotrexate