Modification of MRI pattern of high-grade glioma pseudoprogression in regorafenib therapy

Pseudoprogression (PP) is a diagnostic dilemma in the follow-up of brain high grade gliomas (HGG), and the introduction of new therapies has further complicated its identification in Magnetic Resonance Imaging (MRI). We report a case of pseudoprogression after intraoperative radiotherapy (ioRT) and Regorafenib therapy in a patient with anaplastic astrocytoma recurrence. A 65-year-old man, treated in August 2017 for a right frontal anaplastic astrocytoma, with surgical resection and following radiotherapy and Temozolomide, in October 2019 was again treated for peri-surgical bed recurrence with resection and ioRT followed by Regorafenib therapy, interrupted in February 2020, after the onset of adverse reactions. MRI examination showed a large irregular alteration posterior to the surgical bed, T2 weighted hypointense featuring strong diffusion restriction (low ADC values), with an irregular contrast-enhancement (CE) pattern, and surrounded by a vast vasogenic oedema; Dynamic Susceptibility Contrast (DSC) perfusion imaging (PWI) showed no increase of relative cerebral blood volume (rCBV). Particularly, lesion appeared markedly hypointense and dusty-like on susceptibility weighted images (SWI) probably due to a constant hemorrhagic diapedesis promoted by Regorafenib. Therefore, pseudoprogression was suspected. Follow-up MRI exams showed gradual reduction of SWI and CE abnormalities, but a persistent DWI restriction. Unfortunately, the last MRI control showed a secondary cerebellar localisation of the disease. New therapies are changing MRI pattern in HGG imaging and this case underlines how a multimodality approach is increasingly necessary. In particular, when using anti-VEGF drugs, SWI can have a crucial role in identifying therapy-related haemorrhagic changes.