Bevacizumab and radiotherapy for the treatment of glioblastoma: brothers in arms or unholy alliance?

// Maximilian Niyazi 1,2 , Patrick N. Harter 2,3 , Elke Hattingen 4 , Maya Rottler 1,2 , Louisa von Baumgarten 5 , Martin Proescholdt 6 , Claus Belka 1,2 , Kirsten Lauber 1,2 and Michel Mittelbronn 2,3 1 Department of Radiation Oncology, University of Munich, Germany 2 German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany 3 Institute of Neurology (Edinger Institute), Goethe University, Frankfurt, Germany 4 Department of Neuroradiology, University Hospital Bonn, Bonn, Germany 5 Department of Neurology, University of Munich, Munich, Germany 6 Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany Correspondence to: Kirsten Lauber, email: // Keywords : glioma, radiotherapy, bevacizumab, angiogenesis, VEGF Received : August 19, 2015 Accepted : October 13, 2015 Published : November 13, 2015 Abstract Glioblastoma (GBM) represents the most frequent primary brain tumor in adults and carries a dismal prognosis despite aggressive, multimodal treatment regimens involving maximal resection, radiochemotherapy, and maintenance chemotherapy. Histologically, GBMs are characterized by a high degree of VEGF-mediated vascular proliferation. In consequence, new targeted anti-angiogenic therapies, such as the monoclonal anti-VEGF-A antibody bevacizumab, have proven effective in attenuating tumor (neo)angiogenesis and were shown to possess therapeutic activity in several phase II trials. However, the role of bevacizumab in the context of multimodal therapy approaches appears to be rather complex. This review will give insights into current concepts, limitations, and controversies regarding the molecular mechanisms and the clinical benefits of bevacizumab treatment in combination with radio(chemo)therapy - particularly in face of the results of recent phase III trials, which failed to demonstrate convincing improvements in overall survival (OS).