Pseudoprogression and pseudoresponse in the treatment of gliomas

Treatment response of brain tumours is typically evaluated with gadolinium-enhanced MRI using the Macdonald criteria. These criteria depend on changes in the area of enhancement. However, gadolinium enhancement of brain tumours primarily reflects impairment of the blood-brain barrier.

Combined chemo-irradiation with temozolomide may induce in 20-30% of cases pseudoprogression, defined as an increase of contrast-enhancement and/or oedema on MRI without true tumour progression. Also, full-blown radiation necrosis may be more frequent after combined chemo-irradiation. After treatment with vascular endothelial growth factor receptor signalling pathway inhibitors pseudoresponse is frequent: a decrease in contrast-enhancement of brain tumours on MRI without a decrease of tumour activity. This to some extent explains the high response rate without a major increase in survival after treatment with these agents for recurrent glioblastoma.

Both pseudo-phenomenona confuse the assessment of outcome of brain tumours in clinical practice and in clinical trials. To overcome these issues, alternative endpoints and response criteria are being developed by an international working party [response assessment in neuro-oncology (RANO)]. It is as yet unclear to what extent alternative imaging tools (positron emission tomography and MRI techniques) provide more reliable indicators of outcome.