New Brain Tumor Therapies, New Recurrence Patterns

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Summary and Comment

New Brain Tumor Therapies, New Recurrence Patterns

This informative retrospective study confirms that bevacizumab is active against recurrent malignant gliomas but may alter recurrence patterns.

Although treatment of malignant gliomas with combination temozolomide chemotherapy, irradiation, and surgery has improved survival, prognosis remains poor and recurrence inevitable. Therefore, the search for novel therapeutic targets continues. Bevacizumab, a human monoclonal antibody, targets vascular endothelial growth factor (VEGF), which mediates angiogenesis in gliomas and other cancers. In this study, researchers retrospectively assessed recurrence patterns in 55 patients with recurrent malignant gliomas who received bevacizumab (along with various chemotherapy regimens) and in 19 patients treated with chemotherapy regimens that did not contain bevacizumab.

Among the 44 patients with radiographic data, the radiographic response rate (i.e., complete or partial tumor regression) with bevacizumab was 34.1%. One third of all bevacizumab recipients had reductions in their steroid doses. Judged by blinded imaging review and by quantitative volumetric analysis of recurrence patterns, there was a trend toward a higher ratio of infiltrative tumor to gadolinium-enhancing tumor in bevacizumab responders compared with nonresponders. The authors conclude that bevacizumab may help suppress enhancing tumor recurrence but not infiltrative tumor growth.

Comment: Bevacizumab combined with chemotherapy for recurrent malignant gliomas has produced striking radiographic response rates in previous studies (Clin Cancer Res 2007; 13:1253). However, the dramatic radiographic changes may not reflect true antitumor activity. Research suggests that bevacizumab may significantly reduce tumor capillary permeability and act as a steroid-sparing agent to decrease peritumoral edema. The authors refer to preclinical studies suggesting that glioma cells co-opt existing cerebral vasculature as an alternative to angiogenesis when VEGF-mediated tumor angiogenesis is blocked. Thus, the volume of contrast enhancement may remain stable, but abnormal FLAIR intensity may increase, reflecting an increase in infiltrating tumor.

The valuable observations in this study are limited by the small number of patients, differing steroid doses and chemotherapy regimens, and lack of definitive differentiation between infiltrating tumor, radiation-related gliosis, and treatment-related leukoencephalopathy in the bevacizumab-treated patients. Nevertheless, they confirm the safety and potential of bevacizumab in glioma therapy, and they highlight potential changes in radiographic tumor-recurrence patterns of which neurologists must be aware.

— Amy A. Pruitt, MD

Published in Journal Watch Neurology May 6, 2008