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."
|