gms | German Medical Science

Objective: Over the past decades there are tremendous advances in the diagnostic and therapeutic approaches to pediatric brain tumors. A better understanding of the pathogenesis leads to the development of new risk stratifications and adapted individualized therapies. We show the increased importance of molecular analysis in diagnostic and therapeutic management by means of 5 children.

Methods: We present 5 children aged between 3 month and 13 years (3 males and 2 females). The first patient suffered from a metastasized medulloblastoma (molecular subgroup 3), second and third patient had a from glioblastoma WHO IV°and the fourth one a desmoplastic infantile ganglioglioma (DIG) and fifth patient was diagnosed an embryonal tumor with abundant rosettes (ETANTR). Case 1 had a “complete” tumor resection followed by chemo-/radiotherapy with complete remission. 3 years later a local relapse was suspected with histology of medulloblastoma. In the case 2 total and in case 3 an incomplete tumor resection was performed by chemo- and radiotherapy. In case 4 a partial tumor resection was followed by chemotherapy, histology was DIG.

Results: All tumors had a molecular analysis which give new diagnosis aspects, a change in further treatments or individualized drug therapy. The molecular analysis in case 1 diagnosed a GBM, which means a second tumor manifestation and not a relapse of medulloblastoma. The followed therapy was according to this adapted. Case 2 showed a pilocytic astrocytoma and was interpreted as GBM with low profile. Follow up over 4 years showed no relapse. Molecular analysis of case 3 showed a low grade glioma whereas histopathologically a GBM was suspected. There was no tumor relapse after follow up of 5 years. The tumor of case 4 could not be completely resected. Molecular analysis showed a BRAF V600E mutation. 1y after chemotherapy further tumor progress developed. An individualized therapy with BRAF-inhibitor (Vemurafemib) resulted in an extensive tumor shrinking. The molecular analysis of case 5 showed an embryonal tumor with multilayered rosettes (ETMR). 1 year later tumor relapse, combined chemo- and radiotherapy was given. Some month later there was again tumor growth with additional tumor resection.

Conclusion: Significant progress has been made in the treatment of pediatric brain tumors over the past decades but the treatment related morbidity remains high and long-term squeal are common. A better understanding of the tumor biology including their molecular features will identify promising therapeutic targets and offers new and risk adapted therapeutic approaches to improve overall survival, decrease in long-term morbidity and side effects of the therapy of pediatric brain tumors.