gms | German Medical Science

Objective: To describe the unique pattern of recurrent glioblastoma after treatment with an antibody against the vascular endothelial growth factor (bevacizumab), which is a very effective anti-angiogenic treatment.

Methods: The institutional series were reviewed for patients, who failed after the standard treatment for glioblastoma (2 cases) or additional resection of recurrent tumor (4 cases) and were then given bevacizumab plus irinotecan (CPT-11).

Results: Six patients were identified, who were given the above mentioned treatment. In all but one case, there was a dramatic initial radiological response with reduction of edema and almost complete resolution of contrast enhancement over six weeks. In one case the tumor progressed regardless of treatment. In the other cases, after a complete resolution of edema associated symptoms, gradual deterioration set in. The magnetic resonance images of two of these patients showed a highly infiltrative tumor resembling gliomatosis cerebri while the other tumors progressed in a more nodular and barely enhancing growth pattern.

Conclusions: While well tolerated, the combination treatment of bevacizumab and irinotecan shows differential effects on the growth pattern of progressive glioblastoma. As reported by others as well, the growth patttern is diffusely infiltrative and much more so than in the early course of the individual`s disease, indicating a shift to another mechanism of dissemination. Prior animal experimentation with anti-VEGF therapy had already indicated that there may be a shift to a vessel-cooptive growth pattern or a kind of "forced" invasion. Although this effect is worrisome, it is offset by the remarkable intial response of the patients and their excellent quality of life in an otherwise desparate stage of the disease. It also remains an interesting question as to why that pattern does not seem to be uniform and whether larger series with stringent correlative analysis of the molecular genetic characteristics of these tumors will allow a substratification which can predict the effects of anti-VEGF treatment on invasiveness of recurrent glioblastoma. These observations have profound clinical implications as they point towards the potential downsides of anti-angiogenic treatment and the necessity of investigating collateral agents as well which may abrogate these undesired effects.