Abstract
BackgroundPerfusion 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.Methods42 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.ResultsAn 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.ConclusionsOur 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.
Highlights
Glioblastomas (GBM) are highly vascularized tumors, leading to development of therapeutic strategies targeting tumor angiogenesis [1]
Despite the significant number of studies based on GBM treatment with bevacizumab, alone or in combination with other drugs, in vivo modifications induced by treatment are poorly defined [3]
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
Summary
Glioblastomas (GBM) are highly vascularized tumors, leading to development of therapeutic strategies targeting tumor angiogenesis [1]. Bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor (VEGF), has recently entered into the clinical arena and represents the front-runner among currently available antiangiogenic drugs [2]. Sorensen, studying recurrent GBM patients treated with cediranib, an inhibitor of the VEGF receptor tyrosine kinases, calculated a ‘‘vascular normalization index’’ by combining Ktrans (the rate of transfer of the contrast agent (CA)), microvessel volume and circulating collagen IV and found that this index (measured 1 day after treatment initiation) was predictive of overall and progression-free survival (OS and PFS) [5]. 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
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