Parametric response maps of perfusion MRI may identify recurrent glioblastomas responsive to bevacizumab and irinotecan

Abstract

Background: Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome.

Methods: 42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged.

Results: An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38), whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04), and re-increased progressively when patients approached tumor progression.

Conclusions: Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.

Figure 1. Parametric Response Maps creation process.

1) comparison of the rCBV values of a ROI placed on the normal white matter between the baseline and the time point under examination; 2) Classification of increased, decreased and unchanged differences values in the tumor area on the basis of the previously determined thresholds; 3) Chromatic representation of the difference map obtained by the subtraction of the baseline map from the time point one. Red voxels indicate an increase of rCBV, blue a decrease and black voxels are unchanged.

Figure 2. Correlations between PRM_CBV+ higher than 18% and baseline magnetic resonance disease patterns and PFS/OS.

A: Patients with PRM_CBV+ higher than the first quartile, 18%, had longer survival than the others. B: Patients with local pattern of disease at baseline had longer PFS and OS than those with distant or multifocal disease.

Figure 3. Mean rCBV changes according to treatment response within time.

a) Mean rCBV remained elevated in non responsive patients who progressed after 8 weeks of treatment. b) Mean rCBV resulted in a significant decrease at 8 weeks, and in a new increase at 16 weeks, when progression occurred at 16 weeks. c) Mean rCBV showed a decrease at 8 weeks also in patients who progressed at 24 weeks or later but in the following MR performed before progression a light continuous increase of rCBV was observed.