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Identification of the EGFRvIII mutation in glioblastoma by magnetic resonance perfusion-weighted imaging (MR-PWI) and VEGF expression helps guide treatment decisions

Magnetic resonance perfusion-weighted imaging (MR-PWI) may be a useful tool to help make rational treatment decisions based on its ability to accurately identify genetic mutations in malignant brain tumors, according to researchers from the University of Pennsylvania.

"To my knowledge this is the first demonstration that an MRI technique, or any imaging technique, can predict with very high specificity and positive predictive value the mutational status of a human tumor," said Donald M. O'Rourke, M.D., associate professor of neurosurgery at the University of Pennsylvania, Philadelphia.

The aim of this study was to determine the accuracy of relative cerebral blood volume (rCBV) and vascular endothelial growth factor (VEGF) measurements in an effort to identify the frequent genetic alterations of the epidermal growth factor receptor (EGFR) in patients with gliobastoma; the most prevalent EGFR genetic alteration is known as EGFRvIII. MR-PWI is a method of assessing blood flow to discriminate between higher grade gliomas, including glioblastomas, and less malignant forms.

O'Rourke and colleagues analyzed tissue samples from 97 participants and used real-time polymerase chain reaction to evaluate VEGF expression. Findings showed higher rCBV values using MR-PWI in patients with EGFRvIII compared to those who did not have the genetic mutation.

"We were not so surprised the cerebral blood volume correlated with this particular EGFR mutation because the cerebral blood volume value has been previously shown by our group to correlate with high-grade versus low-grade tumors, and EGFRvIII tumors are the most malignant type of glioblastomas," O'Rourke said. "We were somewhat surprised that VEGF was not the only variable to explain the elevation in cerebral blood volume. I didn't expect there to be such robust data behind it."

Advanced imaging modalities, such as MR-PWI, may provide non-invasive surrogate markers for EGFRvIII and, ultimately, other glioblastoma mutations, and potentially aid in the facilitation of treatment selection for patients, according to O'Rourke.

"If we are able to substantiate these findings and see the perfusion value changing while we are treating the patient, then we will know if we should continue with treatments directed against EGFRvIII or switch to alternative treatment strategies for our patients with malignant gliomas," he said. "These findings are potentially powerful, but provocative; MRI could serve as a non-invasive way to predict glioblastoma subtypes, select the best therapy for the patient and monitor its success over time."


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