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Pseudoresponse

KEY FACTS

TERMINOLOGY

• Antiangiogenic agents may substantially reduce contrast

enhancement in glioblastoma multiforme related to

reduced vascular permeability rather than actual tumor

response

○ Bevacizumab (Avastin): Anti-VEGF is main antiangiogenic

agent currently used for treatment of recurrent

malignant gliomas

○ Cediranib: VEGF receptor tyrosine kinase inhibitor has

been tested in recent high-grade glioma treatment trials

IMAGING

• Decreased enhancement in patient with malignant glioma

treated with anti-VEGF agent

○ May see persistent FLAIR and diffusion restriction,

despite decreased enhancement

• DWI and ADC have been proposed as imaging markers for

tumor response in presence of antiangiogenic agents to

address pseudoresponse

• Beware, decreased enhancement in tumor follow-up study

may be true treatment response or pseudoresponse in

setting of newer therapies

• DSC: Early changes in relative cerebral blood volume after

initiation of antiangiogenic therapy may distinguish

pseudoresponse from true treatment response

TOP DIFFERENTIAL DIAGNOSES

• Treatment response

• Steroid effect

CLINICAL ISSUES

• Antiangiogenic agents normalize hyperpermeable tumor

vasculature and restore blood-brain barrier

• Local response to tumor growth is controlled, but diffuse

infiltration and distant metastases are common

• Antiangiogenic agents significantly improve 6-month

progression-free survival but may not affect overall survival

(Left) Axial T1 C+ MR in a GBM

patient who progressed on

standard therapy with

radiation and Temodar shows

there is a heterogeneously

enhancing mass involving the

genu of the corpus callosum

﬇. Avastin therapy was

started immediately after this

MR examination. (Right) Axial

T1 C+ MR in the same patient

4 weeks after the start of

Avastin shows a marked

decrease in the enhancing

mass involving the genu of the

corpus callosum ﬇. The FLAIR

and DWI showed stable

hyperintensity and mass

effect.

(Left) Axial T1 C+ MR in the

same patient 8 weeks later

shows an increase in the size

of the corpus callosum

enhancing mass ﬇. (Right)

Axial FLAIR MR in the same

patient shows a marked

increase in the size ﬇ and

associated mass effect of the

corpus callosum mass related

to progressive tumor.

Decreased enhancement on

the prior MR is a result of

pseudoresponse from the

antiangiogenic therapy, rather

than true tumor response.

Diffuse tumor infiltration is

common after antiangiogenic

therapy.

Brain: Pathology-Based Diagnoses: Neoplasms,

Cysts, and Disorders