Early Biomarkers from Conventional and Delayed-Contrast MRI to Predict the Response to Bevacizumab in Recurrent High-Grade Gliomas

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Twenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment with standard and delayed-contrast MRI. The mean change in lesion volumes of responders (overall survival, >1 year) and nonresponders (overall survival, <1 year) was evaluated. Treatment-response-assessment maps (TRAMs) were calculated by subtracting conventional T1WI (acquired a few minutes postcontrast) from delayed T1WI (acquired with a delay of >1 hour postcontrast). These maps depict the spatial distribution of contrast accumulation and clearance. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI. The authors conclude that the benefit of standard and delayed-contrast MRI for assessing and predicting the response to bevacizumab was demonstrated and that the increased sensitivity of delayed-contrast MRI reflects its potential contribution to the management of bevacizumab-treated patients with recurrent HGG.

Abstract

Figure 1 from paper
Examples demonstrating that the response to bevacizumab is independent of pretreatment tumor volumes: Shown are axial contrast-enhanced T1-weighted MRIs and TRAMs calculated 5 days before bevacizumab treatment and 79 days post-initiation of treatment of a nonresponding patient (left) with a relatively small pretreatment tumor. Also shown are contrast-enhanced T1-weighted MRIs and TRAMs calculated 7 days before bevacizumab treatment and 387 days post-initiation of treatment of a responding patient (right) with a relatively large pretreatment tumor. One month after the initiation of treatment, the nonresponding patient’s tumor volumes increased (blue up to 131% of initial volume, and T1, up to 103%). Despite the large initial tumor volume, the responding patient showed significant reduction in tumor volume (blue down to 21% of initial volume, and T1, down to 25%), which remained low for >15 months posttherapy. Both patients showed decreased FLAIR volumes.

BACKGROUND AND PURPOSE

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.

MATERIALS AND METHODS

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 progression, the average change in lesion volume from previous follow-up in standard and delayed-contrast MRIs was compared.

RESULTS

Response and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast-enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response-assessment maps.

CONCLUSIONS

The benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma.

 

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Early Biomarkers from Conventional and Delayed-Contrast MRI to Predict the Response to Bevacizumab in Recurrent High-Grade Gliomas
Jeffrey Ross
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