Facing pseudoprogression after radiotherapy in low grade gliomas

Pseudoprogression has been defined as a transient increase in the contrast enhancement within the treated tumour after radiotherapy, which eventually subsides without any change in the anti-cancer therapy (1,2). This constitutes most likely a subacute post-treatment effect of radiotherapy characterised by a local inflammatory reaction on tumour cells and/or vascular injury resulting in increased permeability (1,2). The concept of pseudoprogression was initially developed in adults with high-grade gliomas treated with radiotherapy +/− alkylating agents (3); and it has subsequently been extended to other brain tumours, including low-grade gliomas (LGG). Pseudoprogression has been reported to occur more frequently when temozolomide is combined with radiotherapy (4,5), although the magnitude of this effect yet remains to be established (3). Pseudoprogression can produce a clinical impact both at an individual and at a population level. Firstly, increased contrast enhancement in adults with LGG is highly suggestive of malignant transformation (6), so undiagnosed pseudoprogression may cause major distress for the patients and their families, and can even result in initiation of a new anti-cancer therapy inappropriately. Secondly, because failure to exclude patients with pseudoprogression at the time of enrolment in clinical trials may lead to falsely elevated response rates (1). And finally, because failure to identify pseudoprogression whilst on trial, limits the validity of progression-free survival as a primary endpoint (1). Hence, a better understanding and diagnosis of pseudoprogression is crucial to ensure adequate clinical management and to minimise hindrance to clinical trials.