Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology.

TY - JOUR

T1 - Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology.

AU - von Bueren, André

AU - von Hoff, Katja

AU - von Hoff, Katja

AU - Pietsch, Torsten

AU - Gerber, Nicolas U

AU - Warmuth-Metz, Monika

AU - Deinlein, Frank

AU - Zwiener, Isabella

AU - Faldum, Andreas

AU - Fleischhack, Gudrun

AU - Benesch, Martin

AU - Krauss, Juergen

AU - Kuehl, Joachim

AU - Rutkowski, Stefan

AU - Rutkowski, Stefan

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Humans

KW - Male

KW - Female

KW - Prospective Studies

KW - Prognosis

KW - Survival Rate

KW - Follow-Up Studies

KW - Combined Modality Therapy

KW - Child, Preschool

KW - Infant

KW - Magnetic Resonance Imaging

KW - Remission Induction

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Carboplatin/administration & dosage

KW - Cerebellar Neoplasms/pathology/therapy

KW - Cyclophosphamide/administration & dosage

KW - Etoposide/administration & dosage

KW - Leucovorin/administration & dosage

KW - Medulloblastoma/pathology/therapy

KW - Methotrexate/administration & dosage

KW - Neoplasm Recurrence, Local/pathology/therapy

KW - Radiotherapy

KW - Vincristine/administration & dosage

KW - Humans

KW - Male

KW - Female

KW - Prospective Studies

KW - Prognosis

KW - Survival Rate

KW - Follow-Up Studies

KW - Combined Modality Therapy

KW - Child, Preschool

KW - Infant

KW - Magnetic Resonance Imaging

KW - Remission Induction

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Carboplatin/administration & dosage

KW - Cerebellar Neoplasms/pathology/therapy

KW - Cyclophosphamide/administration & dosage

KW - Etoposide/administration & dosage

KW - Leucovorin/administration & dosage

KW - Medulloblastoma/pathology/therapy

KW - Methotrexate/administration & dosage

KW - Neoplasm Recurrence, Local/pathology/therapy

KW - Radiotherapy

KW - Vincristine/administration & dosage

M3 - SCORING: Journal article

VL - 13

SP - 669

EP - 679

JO - NEURO-ONCOLOGY

JF - NEURO-ONCOLOGY

SN - 1522-8517

IS - 6

M1 - 6

ER -