MR spectroscopic imaging predicts early response to anti-angiogenic therapy in recurrent glioblastoma (original) (raw)
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Neuro-Oncology, 2013
Background. The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy. Methods. Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan. Patients were scanned prior to treatment and at specific timepoints during the treatment regimen. Postcontrast T1-weighted MRI was used to assess 6-month progression-free survival. Spectra from the enhancing tumor and peritumoral regions were defined on the postcontrast T1-weighted images. Changes in the concentration ratios of N-acetylaspartate/creatine (NAA/Cr), cholinecontaining compounds (Cho)/Cr, and NAA/Cho were quantified in comparison with pretreatment values. Results. NAA/Cho levels increased and Cho/Cr levels decreased within enhancing tumor at 2 weeks relative to pretreatment levels (P ¼ .048 and P ¼ .016, respectively), suggesting a possible antitumor effect of bevacizumab with cytotoxic chemotherapy. Nine of the 13 patients were alive and progression free at 6 months. Analysis of receiver operating characteristic curves for NAA/Cho changes in tumor at 8 weeks revealed higher levels in patients progression free at 6 months (area under the curve ¼ 0.85), suggesting that NAA/Cho is associated with treatment response. Similar results were observed for receiver operating characteristic curve analyses against 1-year survival. In addition, decreased Cho/Cr and increased NAA/Cr and NAA/Cho in tumor periphery at 16 weeks posttreatment were associated with both 6-month progression-free survival and 1-year survival. Conclusion. Changes in NAA and Cho by MR spectroscopy may potentially be useful as imaging biomarkers in assessing response to anti-angiogenic treatment.
Neuro-Oncology, 2013
Background. The objective of this study was to examine the predictive value of parameters of 3D 1 H magnetic resonance spectroscopic imaging (MRSI) prior to treatment with radiation/chemotherapy (baseline) and at a postradiation 2-month follow-up (F2mo) in relationship to 6-month progression-free survival (PFS6) and overall survival (OS). Methods. Sixty-four patients with newly diagnosed glioblastoma multiforme (GBM) being treated with radiation and concurrent chemotherapy were involved in this study. Evaluated were metabolite indices and metabolite ratios. Logistic linear regression and Cox proportional hazards models were utilized to evaluate PFS6 and OS, respectively. These analyses were adjusted by age and MR scanner field strength (1.5 T or 3 T). Stepwise regression was performed to determine a subset of the most relevant variables. Results. Associated with shorter PFS6 were a decrease in the ratio of N-acetyl aspartate to choline-containing compounds (NAA/Cho) in the region with a Cho-to-NAA index (CNI) .3 at baseline and an increase of the CNI within elevated CNI regions (.2) at F2mo. Patients with higher normalized lipid and lactate at either time point had significantly worse OS. Patients who had larger volumes with abnormal CNI at F2mo had worse PFS6 and OS. Conclusions. Our study found more 3D MRSI parameters that predicted PFS6 and OS for patients with GBM than did anatomic, diffusion, or perfusion imaging, which were previously evaluated in the same population of patients.
Journal of neuro-oncology, 2016
Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor response to bevacizumab is complex and there is no validated method of monitoring tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the effectiveness of bevacizumab with or without carboplatin in patients with rGBM. Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate relative cerebral blood volume (rCBV) histogram statistics of the contrast-enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load) was developed to estimate the total volume of perfused tumor blood vessels. Changes in all rCBV measures were examined for correlations with progression-free (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET trial were included. Median PFS and OS were 23 an...
PLoS ONE, 2014
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 (PRM CBV+) 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 (4.860.9 versus 5.161.2, p = 0.38), whereas decreased in responsive patients (4.261.3 versus 3.861.6 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.
American Journal of Neuroradiology, 2012
BACKGROUND AND PURPOSE: SIACI of bevacizumab has emerged as a promising novel therapy in the treatment of recurrent GB. This study assessed the potential of 1 H-MRS as an adjunctive technique in detecting metabolic changes reflective of antiproliferative effects of targeted infusion of bevacizumab in the treatment of GB. MATERIALS AND METHODS: Eighteen patients enrolled in a phase I/II study of SIACI of bevacizumab for treatment of recurrent GB were included. Concurrent MR imaging and 1 H-MRS scans were performed before and after treatment. Five distinct morphologic ROIs were evaluated for structural and metabolic changes on MR imaging and 1 H-MRS, which included enhancing, nonenhancing T2 hyperintense signal abnormality, and multiple control regions. Pre-and post-SIACI of bevacizumab peak areas for NAA, tCho, tCr, as well as tCho/tCr and tCho/NAA ratios, were derived for all 5 ROIs and compared using the Wilcoxon signed-rank test. RESULTS: A significant median decrease of 25.99% (range Ϫ55.76 to 123.94; P ϭ .006) in tCho/NAA was found post-SIACI of bevacizumab relative to pretreatment values in regions of enhancing disease. A trend-level significant median decrease of 6.45% (range Ϫ23.71 to 37.67; P ϭ .06) was noted in tCho/NAA posttreatment in regions of nonenhancing T2-hyperintense signal abnormality. CONCLUSIONS: The results of this 1 H-MRS analysis suggest that GB treatment with SIACI of bevacizumab may be associated with a direct antiproliferative effect, as demonstrated by significant reductions of tCho/NAA after the intervention. ABBREVIATIONS: GB ϭ glioblastoma; IA ϭ intra-arterial; IDL ϭ Interactive Data Language; Lac ϭ lactate; PFS ϭ progression-free survival; RANO ϭ response assessment in neuro-oncology; SIACI ϭ superselective intra-arterial cerebral infusion; tCho ϭ total choline; tCr ϭ total creatine
AJNR. American journal of neuroradiology, 2016
The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab. Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, ≥1 year) and nonresponders (overall survival, <1 year) was studied. The lesion volumes at baseline and the changes in lesion volumes 1 month after treatment initiation, calculated from standard and delayed-contrast MRIs, were studied as possible predictors of outcome. In scans acquired at progres...
Neuro-Oncology, 2011
Although the effects of bevacizumab on magnetic resonance images (MRIs) of recurrent glioblastoma multiforme (GBM) are well documented, to our knowledge, no studies have explicitly quantified the volumetric changes resulting from initial treatment, nor have there been studies examining the ability for volumetric changes in conventional MRI to predict progressionfree survival (PFS) and overall survival (OS). In the current study, we retrospectively examined volumetric changes on conventional MRI scans in 84 patients with recurrent GBM. MRIs were obtained before (mean, 11 days) and after (mean, 42 days) treatment with bevacizumab. The volume of abnormal fluid-attenuated inversion recovery (FLAIR) signal intensity, the volume of contrast enhancement, and the ratio of the 2 were quantified for each patient before and after initial treatment. Results demonstrated that initial treatment with bevacizumab resulted in a significant decrease in both the volume of abnormal FLAIR signal and the volume of contrast enhancement. Initial, residual, and change in FLAIR volume were not predictive of PFS or OS. Initial contrast-enhancing volume was predictive of PFS but not OS. The pretreatment relative nonenhancing tumor ratio, defined as the ratio of FLAIR to contrast-enhancing volume, was found to be predictive of both PFS and OS.
Journal of Clinical Oncology, 2011
A 79-year-old man with recurrent glioblastoma was treated with bevacizumab (10 mg/kg) and irinotecan (125 mg/m 2) every 2 weeks for 6 months. He did not receive corticosteroids during this period. The patient underwent a multimodal magnetic resonance imaging (MRI) protocol before treatment (D0) and 15, 30, 90, 120, and 180 days after treatment (D15, D30, D90, D120, and D180, respectively). The MRI study was approved by our institutional committee on ethics, and informed consent was obtained from the patient. Before treatment, fluid-attenuated inversion recovery (FLAIR) abnormalities covered almost all of the right hemisphere