Dataset Information

Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma.

ABSTRACT:

Background

To analyze the relevance of dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) derived relative cerebral blood volume (rCBV) analysis for predicting response to bevacizumab (BEV) in patients with recurrent glioblastoma (rGB).

Methods

A total of 127 patients diagnosed with rGB receiving either bevacizumab (71 patients, BEV cohort) or alkylating chemotherapy (56 patients, non-BEV cohort) underwent conventional anatomic MRI and DSC-MRI at baseline and at first follow-up after treatment initiation. The mean rCBV of the contrast-enhancing tumor (cT1) as well as cT1 and fluid-attenuated inversion recovery (FLAIR) volumes at both time points were correlated with progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models, logistic regression, and the log-rank test.

Results

Baseline rCBV was associated with both PFS (hazard ratio [HR] = 1.3; P < .01) and OS (HR = 1.3; P < .01) in the BEV cohort and predicted 6-month PFS in 82% and 12-month OS in 79% of patients, whereas it was not associated with PFS (HR = 1.0; P = .70) or OS (HR = 1.0; P = .47) in the non-BEV cohort. Corresponding median OS and PFS rates in the BEV cohort for patients with rCBV-values less than 3.92 (optimal threshold from receiver operating characteristic [ROC] analysis of 12-month OS data) were 14.2 and 6.0 months, as compared to 6.6 and 2.8 months for patients with rCBV-values greater than 3.92 (P < .01, respectively). cT1 and FLAIR volumes at first follow-up were significant predictors of 6-month PFS and 12-month OS in the BEV cohort but not in the non-BEV cohort. Corresponding volumes at baseline were not significant in any cohort.

Conclusions

Pretreatment rCBV is a potential predictive imaging biomarker in BEV-treated rGB but not alkylating chemotherapy-treated rGB, which is superior to volumetric analysis of conventional anatomic MRI and predicts 6-month PFS and 12-month OS in 80% of BEV-treated patients.

SUBMITTER: Kickingereder P

PROVIDER: S-EPMC4490872 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma.

Kickingereder Philipp P Wiestler Benedikt B Burth Sina S Wick Antje A Nowosielski Martha M Heiland Sabine S Schlemmer Heinz-Peter HP Wick Wolfgang W Bendszus Martin M Radbruch Alexander A

Neuro-oncology 20150309 8

<h4>Background</h4>To analyze the relevance of dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) derived relative cerebral blood volume (rCBV) analysis for predicting response to bevacizumab (BEV) in patients with recurrent glioblastoma (rGB).<h4>Methods</h4>A total of 127 patients diagnosed with rGB receiving either bevacizumab (71 patients, BEV cohort) or alkylating chemotherapy (56 patients, non-BEV cohort) underwent conventional anatomic MRI and DSC-MRI at baseline and at first ...[more]

PMID: 25754089

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Project description:BackgroundAnti-angiogenic therapy with bevacizumab is the most widely used treatment option for recurrent glioblastoma, but therapeutic response varies substantially and effective biomarkers for patient selection are not available. To this end, we determine whether novel quantitative radiomic strategies on the basis of MRI have the potential to noninvasively stratify survival and progression in this patient population.MethodsIn an initial cohort of 126 patients, we identified a distinct set of features representative of the radiographic phenotype on baseline (pretreatment) MRI. These selected features were evaluated on a second cohort of 165 patients from the multicenter BRAIN trial with prospectively acquired clinical and imaging data. Features were evaluated in terms of prognostic value for overall survival (OS), progression-free survival (PFS), and progression within 3, 6, and 9 months using baseline imaging and first follow-up imaging at 6 weeks posttreatment initiation.ResultsMultivariable analysis of features derived at baseline imaging resulted in significant stratification of OS (hazard ratio [HR] = 2.5; log-rank P = 0.001) and PFS (HR = 4.5; log-rank P = 2.1 × 10-5) in validation data. These stratifications were stronger compared with clinical or volumetric covariates (permutation test false discovery rate [FDR] <0.05). Univariable analysis of a prognostic textural heterogeneity feature (information correlation) derived from postcontrast T1-weighted imaging revealed significantly higher scores for patients who progressed within 3 months (Wilcoxon test P = 8.8 × 10-8). Generally, features derived from postcontrast T1-weighted imaging yielded higher prognostic power compared with precontrast enhancing T2-weighted imaging.ConclusionRadiomics provides prognostic value for survival and progression in patients with recurrent glioblastoma receiving bevacizumab treatment. These results could lead to the development of quantitative pretreatment biomarkers to predict benefit from bevacizumab using standard of care imaging.

Project description:BackgroundThe microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification.MethodsData from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples.ResultsSignificant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples.ConclusionsThe proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.

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Dataset Information

Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma.

Background

Methods

Results

Conclusions

Publications

Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma.

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