Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters.

Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed.

Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy.

Background: To assess feasibility, acute toxicity, and efficacy of intraventricular methotrexate administered as part of the primary therapy in medulloblastoma.

Methods: From 2001 to 2007, 240 patients < 22 years from 61 treatment centres were registered. Patients received 2-3 cycles of intraventricular methotrexate with systemic chemotherapy in three different treatment arms of the prospective multicentre trial HIT2000 (150 children > 4 years with metastatic, 59 < 4 years with non-metastatic, 31 < 4 years with metastatic medulloblastoma).

Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol.

Background: Due to the rarity of metastatic medulloblastoma in adults, knowledge about the efficacy and toxicity of intensified chemotherapy and radiotherapy is limited.

Patients And 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.

Neuropsychological short assessment of disease- and treatment-related intelligence deficits in children with brain tumours.

Objective: The Wuerzburger Psychologische Kurz-Diagnostik (WUEP-KD) is a short screening battery for cognitive deficits in children with brain tumour. We report on its psychometric quality and testing efficiency.

Material And Methods: WUEP-KD was founded on Cattell-Horn-Carroll (CHC) framework of cognitive abilities.

Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.

Purpose: The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.

Methods And Materials: After surgery, children received hyperfractionated radiation therapy (36 Gy to the craniospinal axis, 68 Gy to the tumor region, and 72 Gy to any residual tumor, fractionated at 2 × 1 Gy per day 5 days per week) accompanied by weekly intravenous administration of vincristine and followed by 8 cycles of maintenance chemotherapy (lomustine, cisplatin, and vincristine).

Adults with CNS primitive neuroectodermal tumors/pineoblastomas: results of multimodal treatment according to the pediatric HIT 2000 protocol.

Central nervous system primitive neuroectodermal tumors (CNS-PNET) and pineoblastomas (PBL) are rare in adulthood. Knowledge on clinical outcome and the efficacy and toxicities of chemotherapy in addition to radiotherapy is limited. Patients older than 21 years at diagnosis were followed in the observational arm of the prospective pediatric multicenter trial HIT 2000.

Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy.

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.

Treatment of adult nonmetastatic medulloblastoma patients according to the paediatric HIT 2000 protocol: a prospective observational multicentre study.

Background: Medulloblastoma in adulthood is rare. Knowledge is limited, and the efficacy and toxicity of chemotherapy--especially in nonmetastatic disease--is still elusive.

Methods: Seventy adults aged ≥21 years (median age: 28.

A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma.

Background: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population.

Frequency, risk-factors and survival of children with atypical teratoid rhabdoid tumors (AT/RT) of the CNS diagnosed between 1988 and 2004, and registered to the German HIT database.

Purpose: To analyze the frequency, prognostic factors, and outcome of children with atypical teratoid/rhabdoid tumors (AT/RT), a rare and highly malignant embryonal brain tumor.

Materials And Methods: Clinical data of patients diagnosed between 1988 and 2004 with AT/RT who were registered to the German HIT trial center, were correlated with outcome. Patient numbers for AT/RT were compared to numbers for primitive neuroectodermal tumors and medulloblastomas (PNET/MB) registered to the population-based HIT trials.

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

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.

Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91.

Purpose: To analyse long-term outcome and clinical prognostic factors in medulloblastoma.

Methods: We analysed 280 patients with medulloblastoma (3-18 years) included from 1991 to 1997 in the randomised multicentre trial HIT'91 comparing pre-('sandwich') and postradiation ('maintenance') chemotherapy (median follow-up of survivors for 10 years).

Results: In 187 patients with complete staging, overall survival (OS) was higher after maintenance compared to sandwich treatment for M0 (10-year OS 91% and 62%, p=0.

Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy.

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.

Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT'91.

Purpose: To identify better risk stratification systems in childhood medulloblastoma based on clinical factors and analysis of routinely processed formalin-fixed tumor material.

Experimental Design: Formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 were analyzed for DNA amplification of c-myc and N-myc (n=133) and mRNA expression of c-myc and trkC (n=104; compared with human cerebellum) using validated methods of quantitative PCR and reverse transcription-PCR. Results were related to clinical data and outcome.

Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91.

Objective: To analyze the outcome of children with pineoblastoma (PB), treated within the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 of German-speaking countries.

Patients: We report on 11 children suffering from PB. Five children younger than 3 years of age received chemotherapy after surgery until eligible for radiotherapy (HIT-SKK87 and HIT-SKK92).

Treatment of early childhood medulloblastoma by postoperative chemotherapy alone.

Background: The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone.

Methods: After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate.

Simultaneous radiochemotherapy in pediatric patients with high-grade glioma: a phase I study.

Background: Sandwich chemotherapy as first postoperative treatment might cause resistance to ensuing irradiation. Simultaneous radiochemotherapy might prevent this.

Patients And Methods: Twenty-nine children with high-grade glioma were treated from 1997-1999.