Pseudoprogression in high-grade glioma

Abstract

Pseudoprogression is a treatment-related effect seen on imaging in high-grade glioma. Enhancement of gadolinium contrast on control MRI can be misinterpreted as tumor recurrence and is also difficult to distinguish from radiation necrosis. Pseudoprogression is seen in up to 30% after standard treatment for glioblastoma multiforme (GBM), which is radiotherapy concurrent with chemotherapy with temozolomide (TMZ) and adjuvant cycles of TMZ. In this article, the current literature on pseudoprogression in high-grade glioma is reviewed by searches in PubMed. We also present two clinical cases, one of which had medullary pseudoprogression. No articles on this subentity of pseudoprogression were found in PubMed. Standard MRI with gadolinium contrast cannot differentiate between pseudoprogression, tumor recurrence and radiation necrosis. More advanced imaging techniques are often not available. Pseudoprogression seems to be related to methylated promoter of the O(6)--methyl-guanine methyl transferase (MGMT) gene, which is associated with improved treatment effect. Discontinuation or change of therapy on the basis of misinterpretation of MRI as disease progression is thus unfortunate. MRI should be interpreted with caution the first 6 months after standard treatment of high-grade glioma. In a GBM patient with contrast enhancement on MRI but few or no new symptoms and/or stable steroid doses, treatment should be continued and control imaging performed after 2-3 months.

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).…”