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Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Volumetric Analysis of Contrast Enhancement in Patients With Newly Diagnosed Glioblastomas
Max A Saint-Germain1, Mohamed Sherief1, Haris I Sair2,3
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore , Maryland , USA.
Background And Objectives:
The results of chemotherapy trials in patients with newly diagnosed glioblastoma during the past 30 years have been disappointing largely because the blood-brain barrier is extremely effective at restricting drug entry into the brain. This study was designed to estimate the proportion of the tumor volume in patients with newly diagnosed glioblastomas that have sufficient blood-brain barrier disruption to allow the penetration of gadolinium which is where chemotherapy most likely penetrates.
Methods:
Preoperative MRI scans were analyzed from 50 consecutive patients with histologically confirmed newly diagnosed glioblastoma and requisite imaging at a single tertiary-care institution in 2022. Tumor segmentation was performed automatically using the HD-GLIO tool. Nonoverlapping volumes were extracted for the T2/fluid-attenuated inversion-recovery hyperintense, contrast-enhancing, and necrotic segments.
Results:
Patients had a median age of 64.5 years (range 35-85), 62% were male, and the median daily dexamethasone dose at the time of the preoperative MRI was 10 mg (range 0-40). Median volumes of each segment were the following: T2/fluid-attenuated inversion-recovery hyperintense = 54.2 cm 3 (IQR: 24.5-92.4), contrast enhancing = 17.2 cm 3 (IQR: 3.3-33.5), and necrosis = 4.6 cm 3 (IQR: 0.1-15.2). Analysis revealed that only 19% of the preoperative tumor volume was contrast enhancing (IQR: 7.1-29), 74% was T2/fluid-attenuated inversion-recovery hyperintense only (IQR: 56.5-92.5), and 7% was necrotic (IQR: 0.4-12.4).
Conclusion:
This study demonstrates that the gadolinium permeable volume in preoperative patients with glioblastoma makes up only 19% of the total tumor volume. As most cytotoxic and targeted agents are much less likely than gadolinium to cross the blood-brain barrier, it is likely that >80% of the tumor will have very limited exposure to systemically administered drugs. These findings suggest that meaningful improvements in the survival of these patients will require focusing on strategies to improve the delivery of therapeutic concentrations of systemically administered drugs to the large nonenhancing regions of this cancer.
Insights
Chemotherapy struggles to reach glioblastoma tumors due to the blood-brain barrier. Only 19% of tumor volume allows drug penetration, limiting treatment effectiveness for most of the tumor.
Area of Science:
- Neuro-oncology
- Radiology
- Pharmacology
Background:
- Chemotherapy trials for newly diagnosed glioblastoma have yielded disappointing results over the past 30 years.
- The blood-brain barrier (BBB) significantly restricts drug entry into the brain, hindering treatment efficacy.
- Understanding BBB disruption is crucial for improving drug delivery in glioblastoma treatment.
Purpose of the Study:
- To estimate the proportion of tumor volume in newly diagnosed glioblastomas with sufficient BBB disruption for gadolinium penetration.
- To assess the potential drug penetration volume within glioblastoma tumors.
- To inform strategies for enhancing systemic drug delivery to glioblastoma.
Main Methods:
- Analysis of preoperative MRI scans from 50 newly diagnosed glioblastoma patients.
- Automated tumor segmentation using the HD-GLIO tool for T2/fluid-attenuated inversion-recovery hyperintense, contrast-enhancing, and necrotic segments.
- Quantification of non-overlapping tumor segment volumes.
Main Results:
- The median age of patients was 64.5 years, with 62% males.
- Contrast-enhancing tumor volume represented only 19% of the total tumor volume.
- The majority of the tumor volume was T2/fluid-attenuated inversion-recovery hyperintense (74%) or necrotic (7%).
Conclusions:
- Gadolinium-permeable tumor volume in preoperative glioblastoma patients is limited to approximately 19% of the total tumor volume.
- Systemic drugs, less permeable than gadolinium, likely have limited exposure to over 80% of the tumor.
- Improving patient survival necessitates strategies to enhance drug delivery to non-enhancing tumor regions.
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