Changes in Relative Cerebral Blood Volume 1 Month after Radiation-Temozolomide Therapy Can Help Predict Overall Survival in Patients with Glioblastoma1

Department of Imaging Sciences, University of Rochester Medical Center, 601 Elmwood Ave, PO Box 648, Rochester, NY 14642-8648, USA.
Radiology (Impact Factor: 6.87). 08/2010; 256(2):575-84. DOI: 10.1148/radiol.10091440
Source: PubMed


To evaluate perfusion parameter changes in patients with glioblastoma multiforme by comparing the perfusion magnetic resonance (MR) imaging measurements obtained before combined radiation and temozolomide therapy (RT-TMZ) with the follow-up MR imaging measurements obtained 1 month after completion of this treatment.
Institutional review board approval was obtained, and HIPAA guidelines were followed. The data of 36 patients (24 male [median age, 63 years]; 12 female [median age, 59 years]) with glioblastoma multiforme who were treated with RT-TMZ were retrospectively reviewed. The hypothesis was that a change in relative cerebral blood volume (rCBV) 1 month after RT-TMZ is predictive of overall survival. Linear regression analysis was performed to correlate changes in tumor size and perfusion parameters with overall survival. Receiver operating characteristic (ROC) curves were evaluated for 1-year survival. Overall survival was assessed with Kaplan-Meir survival curves and log-rank testing.
Percentage change in rCBV at 1 month after RT-TMZ correlated with overall survival. Increased rCBV after treatment was a strong predictor of poor survival (median survival, 235 days versus 529 days with decreased rCBV) (P < .008, log-rank test). The ROC curves for 1-year survival showed a greater area under the curve (0.806; 95% confidence interval [CI]: 0.698, 0.970) (P = .005) with rCBV than with tumor size (0.556; 95% CI: 0.342, 0.729) (P = .382). The overall survival for patients with increased tumor size, based on Macdonald criteria, was shorter than that for patients who showed no progression (stable or partial response), but the difference was not significant (median survival, 442 days versus 598 days) (P = .761, log-rank test).
Change in rCBV after RT-TMZ appears to correlate with overall survival.

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    • "In addition to the method of interpretation for early radiologic deterioration, when to determine this is also a critical issue because it affects the clinician's decision making regarding whether to switch to salvage therapy for recurrent disease or to continue planned adjuvant therapy. The timing of defining early progression varies from 4 weeks to 6 months1,4,16,21,24). As PsPD was termed "early necrosis" in early reports, many series determined PsPD at 4 weeks after treatment. "
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    ABSTRACT: We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.
    Full-text · Article · Jan 2014 · Journal of Korean Neurosurgical Society
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    • "The conventional approach for analyzing MRI parameters is to determine the percentage change in a summary statistic over the tumor VOI, which may be delineated using qualitative imaging such as T1-Gd and FLAIR images. These summary statistics may include the histogram mean, median, or even percentile of the parameter [14] [15]. We have proposed a physiologically based approach where relative tumor volumes are determined from the segmentation of the tumor histogram based on known physiological values. "
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    ABSTRACT: Studies investigating dynamic susceptibility contrast magnetic resonance imaging-determined relative cerebral blood volume (rCBV) maps as a metric of treatment response assessment have generated conflicting results. We evaluated the potential of various analytical techniques to predict survival of patients with glioma treated with chemoradiation. rCBV maps were acquired in patients with high-grade gliomas at 0, 1, and 3 weeks into chemoradiation therapy. Various analytical techniques were applied to the same cohort of serial rCBV data for early assessment of survival. Three different methodologies were investigated: 1) percentage change of whole tumor statistics (i.e., mean, median, and percentiles), 2) physiological segmentation (low rCBV, medium rCBV, or high rCBV), and 3) a voxel-based approach, parametric response mapping (PRM). All analyses were performed using the same tumor contours, which were determined using contrast-enhanced T1-weighted and fluid attenuated inversion recovery images. The predictive potential of each response metric was assessed at 1-year and overall survival. PRM was the only analytical approach found to generate a response metric significantly predictive of patient 1-year survival. Time of acquisition and contour volume were not found to alter the sensitivity of the PRM approach for predicting overall survival. We have demonstrated the importance of the analytical approach in early response assessment using serial rCBV maps. The PRM analysis shows promise as a unified early and robust imaging biomarker of treatment response in patients diagnosed with high-grade gliomas.
    Full-text · Article · Dec 2013 · Translational oncology
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    • "Most often seen in patients with the concomitant radiochemotherapy, pseudoprogression can also occur in patients treated with radiotherapy or chemotherapy alone. In contrast to tumor progression, pseudoprogression is associated with a favorable prognosis [66–68]. Although follow-up conventional MR imaging studies can validate the initial worsening imaging findings, DSC MR imaging has been shown to be helpful in evaluating treatment effects in the first place. "
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    ABSTRACT: Recent advances in the treatment of cerebral gliomas have increased the demands on noninvasive neuroimaging for the diagnosis, therapeutic planning, tumor monitoring, and patient outcome prediction. In the meantime, improved magnetic resonance (MR) imaging techniques have shown much potentials in evaluating the key pathological features of the gliomas, including cellularity, invasiveness, mitotic activity, angiogenesis, and necrosis, hence, further shedding light on glioma grading before treatment. In this paper, an update of advanced MR imaging techniques is reviewed, and their potential roles as biomarkers of tumor grading are discussed.
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