Brain Tumor’s Genetic Makeup Critical in Treatment, Research Finds

Dr. Daniel Brat of Emory University, lead author of one of the new studies, said genotyping would remove tumor variables.
DONNA MARTIN / EMORY UNIVERSITY
By BENEDICT CAREY

Doctors can more effectively treat many brain tumors by first ascertaining their genetic characteristics, rather than studying tissue samples under a microscope, the standard practice, two teams of researchers reported on Wednesday.

The findings could alter diagnosis and treatment decisions for thousands of patients, experts said, and mark an important advance in so-called precision medicine, in which cancer treatments are customized according to the genetic makeup of the patient’s tumors.

“Prognosis is going to be more accurately delineated by these kinds of genetic subtypes, outstripping the value of looking through a microscope,” said Dr. David J. Langer, the chief of neurosurgery at Lenox Hill Hospital in New York, who was not involved in the research.

Doctors working to treat other types of cancer, particularly breast cancer, have already established genetic subtypes to help guide treatment. The two new papers are a large step in bringing the same approach to brain cancer treatment, Dr. Langer said: “This is really the holy grail, this kind of individualized analysis, and we are beginning to reach that point.”

Some 23,000 Americans develop a brain tumor each year, and about 14,000 die of one annually. The two reports, published in The New England Journal of Medicine, focused on gliomas, which account for roughly a third of brain cancer cases.

Some gliomas become aggressive, like the cancer that recently killed Beau Biden, a son of Vice President Joseph R. Biden Jr. But doctors have not had a rigorous way of identifying which tumors will become deadlier before they do so.

In the new studies — one coordinated by the National Institutes of Health, the other led by the Mayo Clinic and the University of California, San Francisco — research teams performed multiple genetic analyses on 1,380 tumors. Both teams found that the tumors could be grouped into a few categories, which could be determined by looking at a handful of genetic glitches.




Tumors with one genetic profile, for instance, were relatively slow growers and responsive to drug treatment, making them good candidates for chemotherapyalone, rather than combined with radiation. Tumors in another category grew relatively slowly but were not as responsive to drugs, suggesting that combined therapy was best.

And those in a third category were nascent aggressors, for which the prognosis is usually dim. But catching those tumors early will at least give families time to enroll in experimental trials, the researchers said, and will give patients and their families more specific guidance on which treatments and trials may be most suitable.

“These are people who so seek out clinical trials, so this is valuable information for them,” said Dr. Daniel J. Brat, vice chairman of pathology and laboratory medicine at Emory University and lead author of one of the new studies, along with more than 300 other scientists in the Cancer Genome Atlas Research Network.

Genotyping will make research trials more focused, he added, less likely to mix different types of tumors.

Under the current system, doctors examine cancerous tissue and rate it according to several stages and grades. A doctor’s judgment varies “depending on where you were trained, when, and by whom,” Dr. Brat said. By relying more extensively on genetic profiles, “all that variability will go away,” he said.

Previous research had identified these genetic markers as important. Many brain surgeons have used genotyping along with standard biopsy ratings to guide treatment. But the new papers conclude that the genetic markers should be central in diagnosis and prognosis, rather than complementary.

“Both studies can justifiably claim that molecular classification captures the biological features of glioma variants better than” current tissue ratings, wrote Dr. David Ellison, of St. Jude Children’s Research Hospital, in Memphis, in an editorial accompanying the two papers.




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