Ein neues Therapieschema für Glioblastoma multiforme : Ergebnis einer Analyse heutiger Behandlungskonzepte sowie der Biologie und Genetik des Tumors

Abstract

For decades, the treatment of glioblastoma multiforme (GBM) has been among the most challenging fields in oncology. Their genetic heterogeneity, infiltrating growth, the high sensitivity and low regeneration capacity of the surrounding brain tissue and the selective permeability of the blood-brain barrier determine the therapeutic difficulties. A model is presented which explains the multitude of observed genetic variations as defects in redundant elements of the common cellular pathway of the two tumor suppresssors p53 and pRB. To find an answer for the lack of progress in the treatment of GBMs during the last thirty years more than 100 different treatment protocols for GBMs were reviewed. They included unusual fractionation schemes, brachytherapy, intraoperative irradiation, application of neutrons or BNCT, a plethora of chemotherapeutics, as well as novel gene and immunotherapy concepts. This has led to a new proposal with carbon-based ion beam therapy as central element. The multimodality regimen comprises surgery and adjuvant therapy, as well. However, in contrast to conventional treatments the algorithm is changed. The concept envisions an initial in vitro chemosensitivity assay and in case of lacking resistance a chemotherapy step with a BBB permeable drug. Tumor-conform ion beam therapy and a cytoreductive surgical step are to follow. By reducing the overall treatment time, the efficiency should further be increased. The suggested treatment scheme is considered safe. It is expected to yield survival rates which match at least the best results obtained up to now with less interventions at a good quality of life