Brain Tumor Res Treat.  2017 Apr;5(1):1-9. 10.14791/btrt.2017.5.1.1.

Bevacizumab in Recurrent Glioma: Patterns of Treatment Failure and Implications

• Li Y
• Ali S
• Clarke J
• Cha S

• KMID: 2378298
• DOI: http://doi.org/10.14791/btrt.2017.5.1.1

Abstract

Glioblastoma, the most common primary malignant brain tumor in adults, is highly aggressive and associated with a poor prognosis. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, has increasingly been used in the treatment of recurrent glioblastoma. It has achieved excellent rates of radiographic response, but most patients will progress after only a few months. Upon recurrence, tumors may not enhance, secondary to vascular normalization. We describe four patterns of radiographic progression commonly associated with Bevacizumab failure: 1) Distant enhancing tumor, 2) Local tumor progression without enhancement, 3) Diffuse gliomatosis-like infiltration, and 4) Local or multifocal progression, with enhancement. Some have noted an increased incidence of distant or diffuse disease upon recurrence, suggestive of a transition to a more aggressive phenotype, but a review of the literature suggests there is no conclusive evidence that Bevacizumab treatment is associated with an increased rate of distant or diffuse recurrence.

Keyword

Brain neoplasms; Bevacizumab; Vascular endothelial growth factor; Glioma; Glioblastoma; Neuroimaging

MeSH Terms

Adult
Bevacizumab*
Brain Neoplasms
Glioblastoma
Glioma*
Humans
Incidence
Neuroimaging
Phenotype
Prognosis
Receptors, Vascular Endothelial Growth Factor
Recurrence
Treatment Failure*
Vascular Endothelial Growth Factor A
Bevacizumab
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 Pre-treatment and post-treatment axial FLAIR (A and B, respectively) demonstrate decreased vasogenic edema post-treatment (arrows). Pre- and post-treatment axial T1 post-contrast (C and D, respectively) demonstrate decreased contrast enhancement (arrowheads). These findings are consistent with treatment response. FLAIR, fluid-attenuated inversion recovery.

• 

  Fig. 2 Pre-treatment and post-treatment axial (A and B, respectively) FLAIR images demonstrate decreased vasogenic edema post-treatment (arrows). Pre- and post-treatment axial T1 post-contrast images through the site of the index lesion (C and D, respectively) demonstrate decreased enhancement of disease (arrowheads). Pre-and post-treatment axial T1-post contrast images through a location distant from the index lesion (E and F, respectively) demonstrate a new distant enhancing tumor post-treatment (low arrow). Pattern of treatment failure is consistent with distant enhancing tumor. FLAIR, fluid-attenuated inversion recovery.

• 

  Fig. 3 Pre-treatment and post-treatment axial FLAIR images (A and B, respectively) demonstrate decreased vasogenic edema post-treatment (arrows). Pre- and post-treatment axial T1 post-contrast through the level of the index lesion (C and D, respectively) demonstrate decreased enhancement at the site of disease (arrowheads). Pre-and post-treatment axial T1-post contrast images through axial levels cranial to the index lesion (E and F, and G and H, respectively) demonstrate new distant enhancing nodules in a pattern consistent with subependymal spread of disease (long arrows). Pattern of treatment failure is consistent with distant enhancing tumor. FLAIR, fluid-attenuated inversion recovery.

• 

  Fig. 4 Pre-treatment and post-treatment axial FLAIR (A and B, respectively) demonstrates increased mass-like FLAIR hyperintensity post-treatment (arrows). Pre- and post-treatment axial T1 post-contrast through the level of the index lesion (C and D, respectively) demonstrate decreased enhancement of the original disease (arrowheads). Pre- and post-treatment axial DWI (E and F, respectively), and pre- and post-treatment ADC maps (G and H, respectively) demonstrate increased mass-like area of reduced diffusion post-treatment (long arrows). Pattern of treatment failure is consistent with local tumor progression without enhancement. FLAIR, fluid-attenuated inversion recovery; DWI, diffusion weighted image; ADC, apparent diffusion coefficient.

• 

  Fig. 5 Pre- and post-treatment axial T1 post-contrast images (A and B, respectively) demonstrate decreased tumor enhancement post-treatment (arrowheads). Multiple pre-treatment (C, E, G, and I) and post-treatment (D, F, H, and J) axial FLAIR images demonstrate development of a diffuse infiltrative FLAIR hyperintensity in a gliomatosis-like pattern (arrows). Pattern of treatment failure is consistent with diffuse gliomatosis-like tumor infiltration. FLAIR, fluid-attenuated inversion recovery.

• 

  Fig. 6 Pre- and post-treatment axial FLAIR (A and B, respectively) demonstrates increased mass-like FLAIR hyperintensity post-treatment (arrows). Pre- and post-treatment axial DWI (C and D, respectively), and pre- and post-treatment ADC map (E and F, respectively) demonstrate an increased mass-like area of reduced diffusion (long arrows). Pre- and post-treatment axial T1 post-contrast images through the level of the index lesion (G and H, respectively) demonstrate increased enhancement. Pattern of treatment failure is consistent with local or multifocal progression with enhancement (arrowheads). FLAIR, fluid-attenuated inversion recovery; DWI, diffusion weighted image; ADC, apparent diffusion coefficient.

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