Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status

Abstract

Background and purpose: Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.

Materials and methods: New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.

Results: Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258).

Conclusions: The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.

Fig 1.

A–C, A 48-year-old woman with glioblastoma with a methylated MGMT promoter gene has a remote tumor mass on the contrast-enhanced T1-weighted image (A) immediately after the concomitant chemoradiotherapy. MR perfusion image (B) reflects a slight increase of CBV, indicating an rCBV of 1.41 compared with contralateral white matter. After 4 months' continuation of TMZ, enhancement of the lesion decreases without further treatment, which is compatible with pseudoprogression (C). D–F, A 65-year-old man with glioblastoma with unmethylated MGMT has a progressive enhancing lesion involving on the splenium (D). MR perfusion image (E) demonstrates a high increase of CBV indicating an rCBV of 4.38. After 2 months, the lesion shows stronger enhancement and more enlargements, demonstrating real tumor progression (F).

Fig 2.

OS by the presence of the MGMT promoter methylation status (A) and by the presence of pseudoprogression or early tumor progression (B).

Fig 3.

Diagram of the study design.

Fig 4.

ROC curve of rCBV predicting pseudoprogression. The rCBV ratio of >1.49 has an 81.5% sensitivity and 77.8% specificity.