Cerebral blood flow changes after radiation therapy identifies pseudo-progression in diffuse intrinsic pontine gliomas

Abstract

Background

The interval between progression and death in diffuse intrinsic pontine glioma (DIPG) is usually < 6 months. However, reports of longer patient survival following radiotherapy, in the presence of radiological signs of progression, suggest that these cases may be comparable to pseudo-progression observed in adult glioblastoma. Our aim was to identify such cases and compare their multimodal MRI features with those of patients that did not present the same evolution.

Methods

Multimodal MRI of 43 children treated for DIPG were retrospectively selected at four time points: baseline, after-radiotherapy, during true-progression, and at the last-visit. The patients were divided into two groups depending on whether they presented conventional MRI changes that mimicked progression. The apparent diffusion coefficient, arterial spin labelling blood flow (ASL-CBF) and dynamic susceptibility perfusion relative blood volume (DSCrCBV) and flow (DSCrCBF) values were recorded for each tumor voxel, avoiding necrotic areas.

Results

After radiotherapy, 19 patients (44%) showed radiological signs that mimicked progression: 16 survived > 6 months following so-called pseudo-progression, with a median of 8.9 months and a maximum of 35.6 months. All 43 patients exhibited increased blood volume and flow after-radiotherapy, but the 90 ^th percentile of those with signs of pseudo-progression had a greater increase of ASL-CBF (p < 0.001). Survival between the two groups did not differ significantly. During true progression, DSCrCBF and DSCrCBV values increased only in patients that had not experienced pseudo-progression.

Conclusions

Pseudo-progression is a frequent phenomenon in DIPG patients. This condition needs to be recognized before considering treatment discontinuation. In this study, the larger increase of the ASL-CBF ratio after radiotherapy accurately distinguished pseudo-progression from true-progression.