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Glioblastoma is a heterogeneous group of cancers, genetically, molecularly and characteristically on imaging studies. Prior studies have supported the relationship between tumor location and clinical prognosis. These studies have been based on qualitative assessment of tumor location. The purpose of this study was to quantitatively localize tumors and find associations with tumor molecular profiles, patient characteristics and clinical outcomes. The goal would be to finding imaging characteristics that can provide insight into prognosis and guide personalized therapy.
Two cohort populations with glioblastoma were retrospectively examined, one from the Stanford University Medical Center and one from the Cancer Genome Atlas (TCGA). The Stanford population was used for algorithm training, and the TCGA population was used to validate the algorithm. The contrast-enhanced portions of the tumor plus the central necrotic core were included in the analysis. The training cohort was stratified into poor and good survival groups defined by 17 months.
Tumors located in the right periventricular white matter were associated with poor prognosis. The testing cohort confirmed these findings. No voxels were found to be associated with the good survival group. This study affirmed prior studies, which showed that deep white matter tracts and ependymal region were associated with poor prognosis. The authors postulate that the specific laterality related to tumor prognosis may be due to delayed clinical presentation of the tumor. The majority of eloquent function of the brain is typically found in the left hemisphere and therefore, tumors in the right side of the brain may be subclinical for a longer period of time.
The hypoxia pathway enrichment and stem cell PDGFRA amplification were the distinct molecular profiles associated with tumors in the right periatrial white matter. Proangiogenic factors are stimulated by hypoxia, and prior studies have also shown that neural stem cells are maintained in hypoxic niche. These results also support the hypothesis that neural stem cells arise in the subventricular zone, along the lateral ventricle.
In summary, using a voxel-based approach, the study found that tumors located in the right occipitotemporal periatrial white matter were associated with poor prognosis as defined by survival less than 11 months, independent of other clinical variables. They were also able to identify a genomic profile associated with this imaging phenotype. Further research in identifying imaging characteristics associated with particular genomic profile will be needed in the age of precision medicine, where targeted therapies are the future of cancer treatment.
