Q&A: Advances in Brain Tumor Treatment

August 1, 2018

Multiple MRI scans showing cross-sections of the brain, with highlighted areas indicating abnormalities. — A groundbreaking imaging technique allows doctors to track a substance called 2HG that a subset of gliomas overproduces.

Doctors and researchers are making strides every day in the fight against brain cancer. Read on to learn about some of the new developments underway at UT Southwestern.

About one-third of brain tumors are gliomas — cancers that can long lie dormant, then transform into a fast-growing, deadly type called glioblastoma. At UT Southwestern’s Simmons Cancer Center, Peter O’Donnell Jr. Brain Institute, and Advanced Imaging Research Center, researchers have developed a groundbreaking imaging technique that allows doctors to track a substance called 2HG that a subset of gliomas, with IDH1/2 gene mutations, overproduces. We discussed this and other improvements in brain tumor care with neuro-oncologist Elizabeth Maher, M.D., Ph.D., and neurological surgeon Bruce Mickey, M.D.

: Dr. Mickey: In some cases it can be difficult with a conventional MR scan to distinguish between a low-grade brain tumor and an inflammatory process, such as multiple sclerosis. Many times this technology can provide a definite tumor diagnosis and eliminate or delay the need for a biopsy.
Dr. Maher: The ability to provide a definite diagnosis (because the presence of 2HG means the tumor has an IDH mutation) and give general prognosis (because patients with IDH-mutant gliomas have a significantly longer survival than those without the mutation) is helpful to the patient and family at a time when the news of a tumor is so shocking and frightening.

: Dr. Mickey: There is no blood test that can assess brain tumor activity the way prostate-specific antigen (PSA) is used in prostate cancer screening and evaluation. Using an MR scan to measure 2HG in a low-grade glioma can provide similar information. It has been shown in a large group of glioma patients at UT Southwestern that 2HG levels rise as a tumor progresses, and decrease with successful treatment.
Dr. Maher: Sometimes we can’t see a difference over time in standard imaging measures on MRI. Having 2HG levels that are stable or in the undetectable range helps in decision-making regarding when to begin treatment. Also, there are now clinical trials of drugs targeting the IDH-mutant enzyme.
Dr. Mickey: Development of these inhibitors is a promising advance. UT Southwestern was one of only a few medical centers selected for the initial trials of this strategy.
Dr. Maher: The initial study, using (an IDH inhibitor called) AG-120, led to prolonged stable disease in over 60 percent of the patients. We have two long-term patients on study, for 45 months and 35 months.

: Dr. Mickey: The Perfexion and the Icon were designed to allow the Gamma Knife to more efficiently treat patients with both benign and malignant brain tumors. For a patient with cancer elsewhere in the body that has spread to multiple sites in the brain, this new technology concentrates high doses of radiation in each metastatic tumor while keeping the radiation dose to the surrounding normal brain at a low, safe level. This strategy fits nicely with the emphasis of the O’Donnell Brain Institute on brain protection.
[Note: UT Southwestern was the first institution in North Texas to install a Gamma Knife Perfexion, and its later upgrade, the Gamma Knife Icon.]

: Dr. Mickey: There is growing evidence that outcomes are better for brain tumor patients treated by high-volume surgeons in high-volume hospitals. UT Southwestern physicians and surgeons care for large volumes of brain tumor patients and are supported by colleagues in neuroradiology, neuropathology, neuropsychology, and physical medicine and rehabilitation, and by a large team of experienced nurses, nurse practitioners, and physician assistants. Everyone involved shares the goal of providing the best outcome possible for each patient.

A Global Approach

Scientists at UT Southwestern have been sharing their innovative method for tracking the brain cancer biomarker 2HG worldwide. For gliomas with certain (IDH) genetic mutations, 2HG can help reveal when the cancer is advancing and whether it’s responding to treatment.

In 2012, Changho Choi, Ph.D., of the Advanced Imaging Research Center, Elizabeth Maher, M.D., Ph.D., and their colleagues published their magnetic resonance (MR) spectroscopy–based protocol to measure 2HG. Dr. Choi has since worked with MR physicists from academic medical centers on four continents to help them modify their spectroscopy protocols. And in 2016 the team published a study of 136 patients — 76 followed over time — showing the technique was an important clinical tool that could reliably track patients’ cancers.

The research was sparked by a National Institutes of Health (NIH) Challenge Grant that Dr. Maher led. The work had additional support from the NIH, Cancer Prevention and Research Institute of Texas, Annette Strauss Center for Neuro-oncology, AIRC, and UT Southwestern.