title: Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy.
abstract: To investigate the utility of postoperative chemotherapy in delaying radiotherapy and to identify prognostic factors in early childhood medulloblastoma, we studied children younger than 3 years of age registered to the HIT-SKK'87 (Therapieprotokoll für Säuglinge und Kleinkinder mit Hirntumoren [Brain Tumor Radiotherapy for Infants and Toddlers with Medulloblastoma] 1987) trial who received systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse, from 1987 to 1993. Children with postoperative residual tumor or metastatic disease received systemic induction chemotherapy prior to interval chemotherapy. Twenty-nine children were eligible for analyses (median age, 1.7 years; median follow-up, 12.6 years). In children without macroscopic metastases, rates (+/-SEM) for 10-year progression-free survival (PFS) and overall survival (OS) were 52.9% +/- 12.1% and 58.8% +/- 11.9% (complete resection), and 55.6% +/- 16.6% and 66.7% +/- 15.7% (incomplete resection), compared with 0% and 0% in children with macroscopic metastases. Survival was superior in nine children with desmoplastic or extensive nodular histology compared with 20 children with classic medulloblastoma (10-year PFS, 88.9% +/- 10.5% and 30.0% +/- 10.3%, p = 0.003; OS, 88.9% +/- 10.5% and 40.0% +/- 11.0%, p = 0.006). Eleven of 12 children with tumor progression during chemotherapy had classic medulloblastoma. After treatment, IQ scores were inferior compared with nonirradiated children from the subsequent study, HIT-SKK'92. Classic histology, metastatic disease, and male gender were independent adverse risk factors for PFS and OS in 72 children from HIT-SKK'87 and HIT-SKK'92 combined. In terms of survival, craniospinal radiotherapy was successfully delayed especially in young children with medulloblastoma of desmoplastic/extensive nodular histology, which was a strong independent favorable prognostic factor. Because of the neurocognitive deficits of survivors, the emerging concepts to avoid craniospinal radiotherapy should rely on the histological medulloblastoma subtype.
authors.affiliation: Children's University Hospital, University of Wuerzburg, Wuerzburg, Germany. rutkowski@mail.uni-wuerzburg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Nicolas Ulrich
authors.initials: NU
authors.lastname: Gerber
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.forename: Astrid
authors.initials: A
authors.lastname: Gnekow
authors.forename: Udo
authors.initials: U
authors.lastname: Bode
authors.forename: Norbert
authors.initials: N
authors.lastname: Graf
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Johannes E A
authors.initials: JE
authors.lastname: Wolff
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Niels
authors.initials: N
authors.lastname: Soerensen
authors.forename: Angela
authors.initials: A
authors.lastname: Emser
authors.forename: Holger
authors.initials: H
authors.lastname: Ottensmeier
authors.forename: Frank
authors.initials: F
authors.lastname: Deinlein
authors.forename: Paul-Gerhardt
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Joachim
authors.initials: J
authors.lastname: Kuehl
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000628:therapy*; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents