Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival
Background. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods. A total of 12 patie...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/5312426 |
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| author | Prativa Sahoo Paul Frankel Julie Ressler Margarita Gutova Alexander J. Annala Behnam Badie Jana Portnow Karen S. Aboody Massimo D’Apuzzo Russell C. Rockne |
| author_facet | Prativa Sahoo Paul Frankel Julie Ressler Margarita Gutova Alexander J. Annala Behnam Badie Jana Portnow Karen S. Aboody Massimo D’Apuzzo Russell C. Rockne |
| author_sort | Prativa Sahoo |
| collection | DOAJ |
| description | Background. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods. A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964) of NSC-mediated therapy for recurrent high-grade glioma. DCE-MRI data from all patients were collected and analyzed at three time points: MRI#1—day 1 postsurgery/treatment, MRI#2— day 7 ± 3 posttreatment, and MRI#3—one-month follow-up. Plasma volume (Vp), permeability (Ktr), and leakage (λtr) perfusion parameters were calculated by fitting a pharmacokinetic model to the DCE-MRI data. The contrast-enhancing (CE) volume was measured from the last dynamic phase acquired in the DCE sequence. Perfusion parameters and CE at each MRI time point were recorded along with their relative change between MRI#2 and MRI#3 (Δ32). Cox regression was used to analyze patient survival. Results. At MRI#1 and at MRI#3, none of the parameters showed a significant correlation with overall survival (OS). However, at MRI#2, CE and λtr were significantly associated with OS (p<0.05). The relative λtr and Vp from timepoint 2 to timepoint 3 (Δ32λtr and Δ32Vp) were each associated with a higher hazard ratio (p<0.05). All parameters were highly correlated, resulting in a multivariate model for OS including only CE at MRI#2 and Δ32Vp, with an R2 of 0.89. Conclusion. The change in perfusion parameter values from 1 week to 1 month following NSC-mediated therapy combined with contrast-enhancing volume may be a useful biomarker to predict overall survival in patients with recurrent high-grade glioma. |
| format | Article |
| id | doaj-art-1849a097c127456ab3fc67f981591561 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-1849a097c127456ab3fc67f9815915612025-02-03T05:43:32ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/53124265312426Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall SurvivalPrativa Sahoo0Paul Frankel1Julie Ressler2Margarita Gutova3Alexander J. Annala4Behnam Badie5Jana Portnow6Karen S. Aboody7Massimo D’Apuzzo8Russell C. Rockne9Division of Mathematical Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USADivision of Biostatistics, Beckman Research Institute, City of Hope, Duarte, CA, USADiagnostic Radiology, City of Hope, Duarte, CA, USADepartment of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USADepartment of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USADivision of Neurosurgery, City of Hope, Duarte, CA, USADepartment of Medical Oncology & Therapeutics, City of Hope, Duarte, CA, USADepartment of Developmental & Stem Cell Biology, Beckman Research Institute, City of Hope, Duarte, CA, USADepartment of Pathology, City of Hope, Duarte, CA, USADivision of Mathematical Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USABackground. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI-) derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC-) mediated enzyme/prodrug gene therapy. Methods. A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964) of NSC-mediated therapy for recurrent high-grade glioma. DCE-MRI data from all patients were collected and analyzed at three time points: MRI#1—day 1 postsurgery/treatment, MRI#2— day 7 ± 3 posttreatment, and MRI#3—one-month follow-up. Plasma volume (Vp), permeability (Ktr), and leakage (λtr) perfusion parameters were calculated by fitting a pharmacokinetic model to the DCE-MRI data. The contrast-enhancing (CE) volume was measured from the last dynamic phase acquired in the DCE sequence. Perfusion parameters and CE at each MRI time point were recorded along with their relative change between MRI#2 and MRI#3 (Δ32). Cox regression was used to analyze patient survival. Results. At MRI#1 and at MRI#3, none of the parameters showed a significant correlation with overall survival (OS). However, at MRI#2, CE and λtr were significantly associated with OS (p<0.05). The relative λtr and Vp from timepoint 2 to timepoint 3 (Δ32λtr and Δ32Vp) were each associated with a higher hazard ratio (p<0.05). All parameters were highly correlated, resulting in a multivariate model for OS including only CE at MRI#2 and Δ32Vp, with an R2 of 0.89. Conclusion. The change in perfusion parameter values from 1 week to 1 month following NSC-mediated therapy combined with contrast-enhancing volume may be a useful biomarker to predict overall survival in patients with recurrent high-grade glioma.http://dx.doi.org/10.1155/2018/5312426 |
| spellingShingle | Prativa Sahoo Paul Frankel Julie Ressler Margarita Gutova Alexander J. Annala Behnam Badie Jana Portnow Karen S. Aboody Massimo D’Apuzzo Russell C. Rockne Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival Stem Cells International |
| title | Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival |
| title_full | Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival |
| title_fullStr | Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival |
| title_full_unstemmed | Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival |
| title_short | Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival |
| title_sort | early changes in tumor perfusion from t1 weighted dynamic contrast enhanced mri following neural stem cell mediated therapy of recurrent high grade glioma correlate with overall survival |
| url | http://dx.doi.org/10.1155/2018/5312426 |
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