Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.