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.

Expression of FoxM1 Is Required for the Proliferation of Medulloblastoma Cells and Indicates Worse Survival of Patients

“…25), and (v) HIT'87 trial (n ¼ 1; systemic interval chemotherapy until craniospinal radiotherapy was applied at 3 years of age or at relapse; ref. 26). The median age was 9.3 years (range, 0.6-45.6 years).…”

Bortezomib stabilizes NOXA and triggers ROS-associated apoptosis in medulloblastoma

“…Medulloblastoma is the most common malignant brain tumor in childhood [1]. Multimodal therapy with surgical resection, chemotherapy and craniospinal radiation leads to greater than 80% five-year overall survival in averagerisk patients older than 3 years [2][3][4].…”

Évolution de la prise en charge des médulloblastomes de l’enfant et de l’adulte

“…Des modalités de traitement basées sur des protocoles de chimiothérapie seule ont été évaluées [53][54][55][56][57][58]. Ainsi, l'étude pilote allemande HIT'87 a confirmé la possibilité de retarder la radiothérapie grâce à une chimiothérapie postopératoire chez les enfants âgés de moins de 3 ans [59]. Ensuite le protocole HIT'92 a tenté de remplacer l'irradiation par du métho-trexate intraventriculaire [56].…”