New Glioma Test Provides Answers during Surgical Procedures

A new diagnostic test detects certain mutations in glioma tumors during brain surgery and identifies those sensitive to metabolic chemotherapeutic agents.

A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30% of all brain tumors and central nervous system tumors, and 80% of all malignant brain tumors. Lower-grade gliomas are often characterized by mutations in the metabolism-related genes IDH1 (isocitrate dehydrogenase 1) and IDH2 (isocitrate dehydrogenase 2). Patients with glioma carrying mutations in either IDH1 or IDH2 have a relatively favorable survival, compared with patients with glioma with wild-type IDH1/2 genes.

Treating brain cancer and preventing recurrence has proven to be difficult, as the blood-brain barrier represents a considerable hurdle. To get around the blood brain barrier issue, investigators at Brigham and Women's Hospital (Boston, MA, USA), Massachusetts General Hospital (Boston, USA) and the Massachusetts Institute of Technology (Cambridge, MA, USA) hypothesized that application of metabolism-altering therapeutics at the surgical margin would improve tumor control and minimize toxicity. To facilitate this process, they developed an intraoperative diagnostic assay to identify IDH mutations.

The rapid multiplexed genotyping tool they developed was used to analyze previously collected patient samples. Results demonstrated that the assay could detect mutations within 27 minutes. For 75 of the 87 clinically annotated brain tumor specimens tested, the assay detected the presence of one or more mutations.

"The first and perhaps most important step in treatment of brain tumors is the initial operation, or craniotomy, which obtains tissue to make the diagnosis, and, for lower grade lesions, provides a therapeutic benefit from removal of the tumor mass," said senior author Dr. Daniel Cahill, associate professor of neurosurgery at Massachusetts General Hospital. "Prior studies from our group, and others, have shown that aggressive surgery provides a substantial survival benefit for patients with lower-grade gliomas. We sought to build upon this surgical scenario, attempting to further prolong survival for these patients."

The glioma diagnostic test was described in the August 6, 2018, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America.

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