Getting Personalized: Therapeutic Targeting of Brain Tumors Gets Smarter Through Genomics

Personalized medicine services have been part of the toolbox of the Neurological Institute’s Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center since 1999, when 1p chromosome deletion testing was first offered. After adding more and more such services in the ensuing years, the center decided in 2013 to begin offering patients with select brain tumors the option of having their tumor tissue undergo genomic profiling to test for thousands of genetic abnormalities that could potentially impact their treatment.

“As we’ve offered more personalized medicine over the years, we’ve reached the point where it clearly makes sense to perform personalized tumor testing for genetic abnormalities in some cases rather than offer just a few specific tests,” says Gene Barnett, MD, MBA, Director of the Burkhardt Brain Tumor Center, which works closely with Cleveland Clinic’s Taussig Cancer Institute.

A road map to more rational drug selection

The Burkhardt Brain Tumor Center offers genomic profiling primarily for patients with new or recurrent glioblastoma, or atypical or malignant meningioma. It can provide a more rational basis on which to choose drug therapies, be they conventional or investigational, by offering data about particular characteristics that a patient’s tumor may have.

“The genomic profiling is looking for specific pathways within the tumor that we might target,” Dr. Barnett explains. “The results can help us avoid treatments that are not predicted to be helpful while suggesting other treatments that are more likely to be in the patient’s best interest.”

Historically, he says, patients have been treated with a standard drug paradigm or an investigational therapy without knowledge of whether their specific tumor would or would not benefit from that approach.

Tissue analysis at a glance

The tissue analysis uses next-generation sequencing to assess for hundreds of known cancer genes, and results are available in two to three weeks.

The process requires an adequate amount of tumor tissue, so testing cannot be performed for all eligible patients, particularly if they have had a needle biopsy. However, in some cases more invasive or larger biopsies can be performed so that tissue can be submitted for comprehensive testing.

The testing is very sensitive in finding many types of gene abnormalities, Dr. Barnett says. In some cancers, nearly two-thirds of all tissue samples assessed are found to have at least one actionable gene alteration.

Because the profile is of the tumor, not the patient’s own genome, it does not necessarily provide any information about heritability of the patient’s condition.

Where the future lies

The Burkhardt Brain Tumor Center is one of a select number of prominent centers across the country performing genomic profiling of brain tumors to guide treatment. “We are recognizing that an important part of the future lies in molecular testing of these tumors,” Dr. Barnett says.

That future will likely include changes to clinical guidelines to incorporate genomic testing guidance, he adds, but more experience and information are needed first. “This type of testing may very well become part of the standard of care for management of certain tumors, but we’re not there yet.”

Cleveland Clinic is contributing to the insights needed in the interim through participation in a clinical trial of genomic testing across a number of tumor types, including malignant meningiomas and other brain tumors.

No guarantees for individual patients

Meanwhile, Dr. Barnett and his Burkhardt Brain Tumor Center colleagues are focused on refining this personalized medicine service to their patients and assessing its benefits, as there is of course no guarantee that it will generate results useful for guiding therapy for any given patient.

“In some patients, the results have suggested new routes of treatment we would not have considered on our own,” Dr. Barnett says. “But it’s too early to say how effective it is.”