Pseudoprogression after glioma therapy: a comprehensive review

Abstract

Over the last decade, pseudoprogression as a clinically significant entity affecting both glioma patient management and the conduct of clinical trials has been recognized as a significant issue. The authors have summarized the literature relative to the incidence, chronological sequence, therapy-relatedness, impact of O-6-methylguanine-DNA methyltransferase methylation status and clinical features of pseudoprogression. Evidence regarding numerous neuroradiologic techniques to differentiate pseudoprogression from tumor recurrence is summarized. The implications of pseudoprogression on prognosis and clinical trial design are substantial, and are reviewed. Relative to this, the overlapping terms pseudoprogression and radiation necrosis are clarified to produce an appropriate basis for future consideration and research regarding this important biological phenomenon.

Single dose bevacizumab as treatment for symptomatic, corticosteroid-refractory pseudoprogression after chemoradiation therapy for newly diagnosed glioblastoma: A case report

“…Pseudoprogression is best diagnosed through serial MRIs because no established method of imaging is yet capable of providing a definitive diagnosis of true tumor progression versus enhancement changes due to other reasons [2][3][4][5][6][7]. Increased contrast enhancement and peritumoral edema that decrease with time are characteristic of pseudoprogression whereas such changes are stable with bona fide tumor progression.…”

“…After completion of concurrent RT and TMZ (most commonly within the first 3 months after completing treatment, but with a range in occurrence from the first few weeks to 6 months post-treatment), patients with high-grade brain tumors can present with an increase in contrast-enhancing lesion size, followed often by subsequent improvement or stabilization without further treatment [2][3][4][5][6][7]. This subacute treatment-related reaction can occur with or without clinical deterioration, but pseudoprogression is clinically asymptomatic in most patients [13].…”

“…Pseudoprogression can also occur following other chemotherapy regimens, including subsequent to placement of chemotherapy-infused wafers in the surgical cavity, and has been described following boron neutron capture therapy (BNCT) for recurrent malignant gliomas as well [2][3][4][5][6]14].…”

“…It may represent at least in part an active inflammatory response against the tumor, and some studies have found an association between the incidence of pseudoprogression and increased survival [2][3][4][5][6][7]9].…”

“…Pseudoprogression is an early-to-subacute post-treatment effect observed on the imaging of high-grade gliomas usually occurring within the initial three months following the start of chemoradiation therapy [2][3][4][5][6]. The increased gadolinium contrast enhancement on magnetic resonance imaging (MRI) can be misinterpreted as tumor recurrence or radiation necrosis (RN).…”